Supplemental Text 1: SNP report of the rs2403254 locus. The report contains knowledge of all genes within a
500 kbp distance of rs2403254, as retrieved from NCBI-Gene, ConsensusPathDB, UniProtKB, OMIM, Gene
Ontology, TCDB, ExPASy and KEGG database.
-------------------------------------------------------------------------------------SNP rs2403254
Chr 11
18325146
-------------------------------------------------------------------------------------Distance to locus: 0
Gene: 11234 (HPS5)
Chr 11
18300217-18343721 (-)
21833017
Seven mutations (six previously unreported) were described in the HPS1, HPS4, and HPS5 genes among Hermansky-Pudlak Syndrome patients of Mexican, Uruguayan, Honduran, Cuban, Venezuelan, and Salvadoran ancestries.
17301833
Tyrosinase and TYRP1 are mistrafficked, however, and fail to be efficiently delivered to melanosomes of HPS-5 melanocytes
15296495
LAMP-3 distribution was restricted to the perinuclear region in HPS-5 fibroblasts, instead of extending to the periphery
15030569
Component of BLOC-2. Results suggest a common biological basis underlying the pathogenesis of HPS-3, -5 and -6 disease.
Protein: HPS5 (Q9UPZ3)
Hermansky-Pudlak syndrome 5 protein;
GO: 0006996
organelle organization
GO: 0007596
blood coagulation
GO: 0031084
BLOC-2 complex
GO: 0043473
pigmentation
OMIM: 607521 HPS5 GENE; HPS5
OMIM: 614074 HERMANSKY-PUDLAK SYNDROME 5; HPS5
Distance to locus: -18670
LD R2 of rs2403254 with intragenic SNP rs3802967: 1
Gene: 2965 (GTF2H1)
Chr 11
18343816-18388590 (+)
21543505
These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.
20974803
cdk1 phosphorylates p62 in vitro and in vivo at T269 and S272, which is necessary for the maintenance of appropriate cyclin B1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.
18692935
GTF2H1 polymorphisms/haplotypes may contribute to genetic susceptibility to lung cancer.
18270339
Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
15909982
The pleckstrin homology domain from the 62 kDa subunit Tfb1 (residues 1-108) of TFIIH is sufficient for binding to the activation domain of herpes simplex virus protein VP16.
15625236
p62 subunit of TFIIH interacts with TRbeta in a ligand-dependent manner.
14500720
transcription factor b3, previously identified as a component of the transcription factor IIH core complex, is shown instead to be transcription factor b4
Pathway: Nucleotide excision repair - Homo sapiens (human)
(database: KEGG)
Pathway: Basal transcription factors - Homo sapiens (human)
(database: KEGG)
Pathway: Viral carcinogenesis - Homo sapiens (human)
(database: KEGG)
Pathway: Eukaryotic Transcription Initiation
(database: Wikipathways)
Pathway: HIV Life Cycle
(database: Reactome)
Pathway: HIV Infection
(database: Reactome)
Pathway: RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription
(database: Reactome)
Pathway: Transcription
(database: Reactome)
Pathway: Disease
(database: Reactome)
Pathway: Formation of incision complex in GG-NER
(database: Reactome)
Pathway: Dual incision reaction in GG-NER
(database: Reactome)
Pathway: Global Genomic NER (GG-NER)
(database: Reactome)
Pathway: Formation of transcription-coupled NER (TC-NER) repair complex
(database: Reactome)
Pathway: Dual incision reaction in TC-NER
(database: Reactome)
Pathway: Transcription-coupled NER (TC-NER)
(database: Reactome)
Pathway: Nucleotide Excision Repair
(database: Reactome)
Pathway: Formation of the HIV-1 Early Elongation Complex
(database: PID)
Pathway: mRNA Capping
(database: Reactome)
Pathway: Late Phase of HIV Life Cycle
(database: Reactome)
Pathway: AndrogenReceptor
(database: NetPath)
Pathway: RNA Polymerase I Transcription Initiation
(database: Reactome)
Pathway: DNA Repair
(database: Reactome)
Pathway: RNA Polymerase II Promoter Escape
(database: Reactome)
Pathway: RNA Polymerase I Chain Elongation
(database: Reactome)
Pathway: RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
(database: Reactome)
Pathway: Formation of HIV-1 elongation complex in the absence of HIV-1 Tat
(database: PID)
Pathway: RNA Polymerase II Pre-transcription Events
(database: PID)
Pathway: RNA Pol II CTD phosphorylation and interaction with CE
(database: Reactome)
Pathway: Formation of the HIV-1 Early Elongation Complex
(database: Reactome)
Pathway: HIV Transcription Initiation
(database: Reactome)
Pathway: RNA Polymerase II HIV-1 Promoter Escape
(database: PID)
Pathway: RNA Polymerase II HIV Promoter Escape
(database: Reactome)
Pathway: Formation of HIV-1 elongation complex containing HIV-1 Tat
(database: Reactome)
Pathway: Tat-mediated elongation of the HIV-1 transcript
(database: Reactome)
Pathway: Formation of incision complex in GG-NER
(database: PID)
Pathway: HIV Transcription Elongation
(database: Reactome)
Pathway: RNA Polymerase II Transcription Elongation
(database: PID)
Pathway: Formation of HIV elongation complex in the absence of HIV Tat
(database: Reactome)
Pathway: Transcription of the HIV genome
(database: Reactome)
Pathway: mRNA Processing
(database: Reactome)
Pathway: RNA Polymerase I Promoter Clearance
(database: PID)
Pathway: RNA Polymerase I Promoter Clearance
(database: Reactome)
Pathway: Dual incision reaction in GG-NER
(database: PID)
Pathway: RNA Pol II CTD phosphorylation and interaction with CE
(database: PID)
Pathway: RNA Polymerase I Promoter Escape
(database: PID)
Pathway: Formation and Maturation of mRNA Transcript
(database: PID)
Pathway: Formation of HIV-1 elongation complex containing HIV-1 Tat
(database: PID)
Pathway: Formation of the Early Elongation Complex
(database: PID)
Pathway: RNA Polymerase II Pre-transcription Events
(database: Reactome)
Pathway: RNA Polymerase II Promoter Escape
(database: PID)
Pathway: Global Genomic NER (GG-NER)
(database: PID)
Pathway: Dual incision reaction in TC-NER
(database: PID)
Pathway: RNA Polymerase II Transcription Initiation
(database: Reactome)
Pathway: RNA Polymerase II Transcription Initiation And Promoter Clearance
(database: Reactome)
Pathway: HIV-1 Transcription Initiation
(database: PID)
Pathway: Transcription
(database: PID)
Pathway: HIV-1 Transcription Elongation
(database: PID)
Pathway: RNA Pol II CTD phosphorylation and interaction with CE
(database: Reactome)
Pathway: RNA Polymerase I Transcription
(database: PID)
Pathway: RNA Polymerase I Transcription Termination
(database: PID)
Pathway: Transcription-coupled NER (TC-NER)
(database: PID)
Pathway: RNA Polymerase I Promoter Escape
(database: Reactome)
Pathway: Formation of the Early Elongation Complex
(database: Reactome)
Pathway: RNA Polymerase II Transcription
(database: PID)
Pathway: Formation of RNA Pol II elongation complex
(database: Reactome)
Pathway: RNA Polymerase II Transcription Elongation
(database: Reactome)
Pathway: RNA Polymerase II Transcription
(database: Reactome)
Pathway: Gene Expression
(database: Reactome)
Pathway: mRNA Capping
(database: PID)
Pathway: Formation of transcription-coupled NER (TC-NER) repair complex
(database: PID)
Pathway: RNA Polymerase II Transcription Initiation
(database: PID)
Pathway: Tat-mediated elongation of the HIV-1 transcript
(database: PID)
Pathway: RNA Polymerase I Chain Elongation
(database: PID)
Pathway: RNA Polymerase I Transcription Initiation
(database: PID)
Pathway: RNA Polymerase II Transcription Initiation And Promoter Clearance
(database: PID)
Pathway: Formation of RNA Pol II elongation complex
(database: PID)
Pathway: RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
(database: PID)
Pathway: RNA Pol II CTD phosphorylation and interaction with CE
(database: PID)
Pathway: RNA Polymerase I Transcription Termination
(database: Reactome)
Pathway: RNA Polymerase I Transcription
(database: Reactome)
Pathway: Transcription of the HIV genome
(database: PID)
Pathway: mRNA Processing
(database: PID)
Protein: TF2H1 (P32780)
General transcription factor IIH subunit 1;
GO: 0000079
regulation of cyclin-dependent protein serine/threonine kinase activity
GO: 0000439
core TFIIH complex
GO: 0000718
nucleotide-excision repair, DNA damage removal
GO: 0005515
protein binding
GO: 0005654
nucleoplasm
GO: 0005675
holo TFIIH complex
GO: 0006200
ATP catabolic process
GO: 0006281
DNA repair
GO: 0006283
transcription-coupled nucleotide-excision repair
GO: 0006289
nucleotide-excision repair
GO: 0006360
transcription from RNA polymerase I promoter
GO: 0006361
transcription initiation from RNA polymerase I promoter
GO: 0006362
transcription elongation from RNA polymerase I promoter
GO: 0006363
termination of RNA polymerase I transcription
GO: 0006366
transcription from RNA polymerase II promoter
GO: 0006367
transcription initiation from RNA polymerase II promoter
GO: 0006368
transcription elongation from RNA polymerase II promoter
GO: 0006370
7-methylguanosine mRNA capping
GO: 0006468
protein phosphorylation
GO: 0010467
gene expression
GO: 0016032
viral process
GO: 0045944
positive regulation of transcription from RNA polymerase II promoter
GO: 0050434
positive regulation of viral transcription
KO: K03141
transcription initiation factor TFIIH subunit 1
OMIM: 189972 GENERAL TRANSCRIPTION FACTOR IIH, POLYPEPTIDE 1; GTF2H1
Distance to locus: 33622
LD R2 of rs2403254 with intragenic SNP rs12218: 0.62922
Gene: 6288 (SAA1)
Chr 11
18287808-18291524 (+)
23623642
SAA up-regulates Lp-PLA2 production significantly via a FPRL1/MAPKs./PPAR-gamma signaling pathway.
23566403
SAA levels can be associated with clinical phenotypes in multiple sclerosis and neuromyelitis optica.
23454129
SAA stimulates foam cell formation via LOX1 induction, and thus likely contributes to atherogenesis.
23437051
SAA1 gene polymorphisms, consisting of -13T/C single nucleotide polymorphism (SNP) in the 5'-flanking region and SNPs within exon 3 are associated with susceptibility to Familial Mediterranean Fever in the Japanese population.
23391827
a novel STAT3 non-consensus TFBS at nt -75/-66 downstream of the NF-kappaB RE in the SAA1 promoter region that is required for NF-kappaB p65 and STAT3 to activate SAA1 transcription
23357645
variant p.Gly90Asp SAA1 protein eliciting significantly reduced inflammatory responses in macrophages through a reduction in the secretion of inflammatory cytokines.
23300020
High serum SAA level is associated with obesity and estrogen receptor-negative breast tumors.
23255027
Letter: serum amyloid A levels are elevated in venous thromboembolism.
23230824
in acute phase of epilepsy, the serum SAA increased, but after 3 months of treatment, the SAA peak was disappeared.
23223242
Pathogenic serum amyloid A 1.1 shows a long oligomer-rich fibrillation lag phase contrary to the highly amyloidogenic non-pathogenic SAA2.2
23171281
Renal AA-amyloidosis is the predominant cause of renal failure in intravenous drug users. Patients with AA-amyloidosis are more likely to be HIV infected and tend to have a higher rate of repeated systemic infections.
23165195
Lipid-poor SAA, but not high density lipoprotein-associated SAA, stimulates G-CSF production.
22901189
High serum amyloid A expression is associated with benign neoplasm of pancreas.
22827403
Data suggest that serum amyloid protein A (SAA1) level in gestational diabetes is predictive of subclinical atherosclerosis in these women; SAA1 levels correlate with risk factors and may serve as biomarker of future atherosclerotic heart disease.
22771314
SAA levels measured by ELISA in 97 NSCLC patients treated with gefitinib correlated with the clinical outcome of the patients
22768267
The rs12218 single nucleotide polymorphism in the SAA1 gene was associated with SUA levels in Chinese subjects, indicating that carriers of the T allele of rs12218 have a high risk of hyperuricemia.
22766792
Serum amyloid A-positive hepatocellular neoplasms may be a new type of inflammatory hepatocellular tumors in alcoholic patients.
22552174
In patients with persistent Atrial Fibrillation and preserved LVEF, serum amyloid a and CRP levels are independent predictors of AF subacute recurrence rate.
22447522
Serum amyloid A (SAA) induces pentraxin 3 (PTX3) production in rheumatoid synoviocytes.
22371903
Amyloid A (AA) proteins in biopsy samples taken from the stomachs of patients with AA amyloidosis
22367597
findings suggested that SAA was significantly associated with disease duration and gastrointestinal manifestations manifestations in Henoch-Schonlein purpura patients
22341353
Purified ten targeted proteins from sera of patients with various types of advanced stage(stage III-IV)cancers. These proteins were identified as isoforms of the human serum amyloid protein A (SAA) family with or without truncations at their N-terminals.
22300576
Large-scale isotype-specific quantification of Serum amyloid A 1/2 by multiple reaction monitoring in crude sera.
22076945
acute phase SAA may be involved in joint destruction though MMP induction and collagen cleavage in vivo.
22011672
Reactive amyloid A (AA) amyloidosis, one of the most severe complications of RA, is a serious, potentially life-threatening disorder caused by deposition of AA amyloid fibrils in multiple organs.
21953030
report abundance levels of SAA in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits
21876610
Serum amyloid alpha is increased in complicated parapneumonic effusion, and it might be useful as a biomarker for complicated and uncomplicated parapneumonic effusion.
21624307
The genetic polymorphism rs12218 of SAA1 might be a promoting factor for carotid intima media thickness in Han Chinese people.
21569756
the N-terminal region plays a crucial role as a rigid core and the central region facilitates the elongation of fibrils in heparin-induced amyloidogenesis of SAA molecule
21465531
SAA up-regulates PTX3 production via FPRL1 significantly, and thus, contributes to the inflammatory pathogenesis of atherosclerosis.
21449704
CC genotype of rs12218 in the SAA1 gene was associated with decreased ABI in Chinese Han subjects, which indicated that the carriers of CC genotype of rs12218 have high risk of peripheral arterial disease.
21325601
A novel anti-inflammatory role of SAA in the induction of a micro-environment that supports T(reg) expansion at sites of infection or tissue injury, likely to curb (auto)-inflammatory responses.
21309051
Gestational diabetes is associated with loss of natural variation of C-reactive protein and serum amyloid A, suggesting altered modulation of inflammation.
21141971
Data suggest that a higher concentration of SAA can serve as an indicator of lung adenocarcinoma and represents a therapeutic target for the inhibition of lung cancer metastasis.
21124955
These findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels.
21103356
Data show that both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects.
21067563
Intestinal epithelial SAA displays bactericidal properties in vitro and could play a protective role in experimental mouse colitis.
20979827
In Chinese Han people, the genetic polymorphism of SAA1 may reflect the serum concentration of HDL-C.
20964562
The blood levels of serum amyloid A protein and transthyretin were found to be significantly increased in lung cancer patients.
20877498
Serum amyloid A protein was significantly increased in vivax malaria patient's plasma.
20869715
acute-phase Serum Amyloid A has a role in response to metformin treatment in insulin resistant women with the polycystic ovary syndrome
20853849
This study data suggested that SAA activated PPARgamma through extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent COX-2 expression.
20713982
the expression of SAA in human benign and malignant ovarian epithelial tumors
20502455
A differential protein with m/z 11.6 kDa was detected and identified as an isoform of human serum amyloid A (SAA). It was significantly increased by 1822% in lung cancer patients when compared with the healthy controls.
20463814
Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5-7 days prior to the first detection of plasma viral HIV-1 RNA, considerably prior to any elevation in systemic cytokine levels
20435930
A-SAA promotes cell migrational mechanisms and angiogenesis critical to rehumatoid arthritis pathogenesis.
20184536
The infectious group was subdivided into bacterial and viral infections, significantly higher leukocyte, serum amyloid A values were observed.
20177146
The results indicate that SAA stimulates FPR2-mediated activation of p38 MAPK and JNK, which are independent of a pertussis toxin-sensitive G-protein and are essential for SAA-induced CCL2 production.
20061576
Data indicate that SAA1 contributes to the reduced reverse cholesterol transport observed during acute phase responses
20022911
High SAA1 is associated with metastatic renal cell cancer.
19925664
Measuring the oxidation-reduction potential (ORP) of plasma in the critically injured, with injury severity and serum amyloid A (SAA) levels. Results suggest the presence of an oxidative environment in the plasma of critically injured as measured by ORP.
19922330
Results suggest that the relatively high affinity of SAA1.5 for high-density lipoprotein may cause the high serum concentration and may be related to the low susceptibility to amyloidosis.
19850938
During atherogenesis, SAA can amplify the involvement of smooth muscle cells in vascular inflammation and that this can lead to deposition of sPLA(2) and subsequent local changes in lipid homeostasis.
19833744
Results describe a significant inverse correlation between serum amyloid A and IgG levels and anti-SSA antibody titers as well as a trend towards an inverse correlation between SAA and ANA and RF titers, but not between CRP and these autoantibodies.
19758820
serum levels of SAA are strongly correlated with serum levels of inflammatory markers as well as measures of glycemic control
19755416
hepatic serum amyloid A expression is enhanced via protein kinase A-dependent mechanism
19729864
Associations of SAA1 and SAAP2 SNPs with carotid artery intima-media thickness, HDL and total cardiovascular disease events
19726303
SAA levels are elevated in obstructive sleep apnea syndrome patients in close correlation to the severity of OSAS, which may contribute to the vulnerability of the patients to cardiovascular diseases
19549924
a highly conserved motif required for SAA binding to macrophages can, under acidic pH conditions and in an heparan sulfate -dependent manner, also act as a molecular switch, directing SAA misfolding into AA amyloid.
19453393
High expression of SAA in carcinomas was detected mostly in tumor cells, but not in normal mucosa. AG490, inhibitor of STAT3 activation, reduced SAA1 expression in SAS cells. SAA was up-regulated in HNSCC through the Janus kinase-STAT3 pathway
19171342
haptoglobin and serum amyloid A may have roles in atherothrombotic ischemic stroke
19167353
SAA stimulates CCL2 production via FPRL1 and, thus, contributes to atherosclerosis.
19007930
A novel oxidized low-density lipoprotein marker, serum amyloid A-LDL, is associated with obesity and the metabolic syndrome.
18768891
SAA, an endogenous ligand of the chemokine formyl peptide receptor-like 1 (FPRL1), stimulates CCL2 production in human monocytes by activating extracellular-signal regulated kinase (ERK) and NF-kappaB.
18726069
A review of how SAA contributes to tumour development and the acceleration of tumour progression and metastasis is presented.
18695905
up-regulation of SAA protein expression mediates the inhibitory effect of Ganoderma lucidum polysaccharides on tumor cell adhesion to endothelial cells.
18571179
SAA is a prothrombotic and proinflammatory mediator in acute coronary syndrome which may contribute to atherogenesis and its complications
18566366
suggest a potential role for SAA in inflammatory diseases through activation of TLR2
18385816
fifth day of observation but were not good predictors of mortality in septic shock.
18322992
The SAA-RAGE-stimulated NF-kappaB signaling pathway has an important role in the pathogenesis of rheumatoid arthritis.
18299466
The association between SAA and leptin suggests an interaction between these two adipokines, which may have implications in inflammatory processes related to obesity and the metabolic syndrome
17968686
Analysis of SAA1 gene polymorphisms showed the rarity of the putative amyloidogenic -13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.
17849429
we first show that SAA1 (coding for the major SAA isoform) but not SAA2 transcripts are expressed in human trabecular and cortical bone fractions and bone marrow.
17806085
SSA1 protein was identified in the blood of colon neoplasm patients.
17676666
SAA was quantitated using PVDF affinity probes and MALD-MS.
17552057
There is a relative deficiency of circulating cystatin C (CysC) in systemic inflammation in rheumatoid arthritis. Interaction between CysC and serum amyloid A protein explains this CysC deficiency and suggests CysC is regulating inflammatory responses.
17461519
SAA can be used as a valuable indicator of disease activity in ankylosing spondylitis.
17329325
SAA reduces hepatitis C virus (HCV) infectivity in a dose-dependent manner when added during HCV infection but not after virus entry.
17237436
SAA induced TF mRNA in PBMC within 30 min and optimal procoagulant activity within 4 h through activation of NF-kappaB via the ERK1/2 and p38 MAPK pathways. SAA-induced TF was partially inhibited by high-density lipoprotein.
17039260
the SAA1 alpha/alpha genotype is a risk factor for amyloidosis in BD
17015746
binding of SAA to FPRL1 may contribute to the destruction of bone and cartilage via the promotion of synoviocyte hyperplasia and angiogenesis
16864904
serum amyloid A and C-reactive protein are expressed differently in exudates and transudates
16737350
Increased expression of SAA1 by adipocytes in obesity may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities.
16651021
Data show that serum amyloid A dissociates apolipoprotein E from high density lipoprotein in cerebrospinal fluid.
16236134
We provide evidence that STAT3 plays an essential role in cytokine-driven SAA expression, although the human SAA gene shows no typical STAT3 response element.
16155472
Within a subsample from the BELSTRESS study of 892 male subjects free of cardiovascular disease, dimensions of job stress from the job demand-control-support model were related to biomarkers of inflammation and infection.
16120612
Serum amyloid A has a role in promoting cholesterol efflux mediated by scavenger receptor B-I
15972323
Increased amyloid AA is associated with amyloidosis and familial Mediterranean fever
15910745
In this study, the SAA4 protein was examined in the high-density lipoprotein fraction of both healthy and diseased individuals.
15729583
SAA is expressed by subcutaneous white adipose tissue and its production at this site is regulated by nutritional status.
15561721
SR-BI plays a key role in SAA metabolism through its ability to interact with and internalize SAA and SAA influences HDL cholesterol metabolism through its inhibitory effects on SR-BI-mediated selective lipid uptake
15225640
Human hepatocytes stimulated by Lipopolysaccharide produced serum amyloid A protein.
15188355
The up-regulation of the A-SAA and FPRL1 genes in inflamed synovial tissue suggests an important role in the pathophysiology of inflammatory arthritis.
15170927
SAA1a/a genotype is one genetic factor that confers a significant risk for amyloidosis in the Turkish FMF population but neither SAA1 nor SAA2 genotypes had a significant effect on SAA level.
15161744
Positive relationship between Tanis mRNA and the acute-phase protein serum amyloid A suggests an interaction between innate immune system responses and Tanis expression in muscle and adipose tissue.
14871291
Saa1 is regulated by tumor necrosis factor-alpha, interleukin-6 and glucocorticoids in hepatic and epithelial cells
14738910
Results indicate a novel role for interleukin-18 in rheumatoid inflammation through the synovial serum amyloid A production.
12762136
Data show higher SAA1 homozygosity in familial Mediterranean fever (FMF)-amyloidosis patients than in FMF patients, but no significant difference between controls and FMF patients with and without amyloidosis for the TNF-alpha-308 G-A allele.
12762135
Data suggest that the frequency of the -13T serum amyloid A1 (SAA1) allele may explain the difference in prevalence of AA amyloidosis in Japanese and Caucasians.
12410800
the region containing the C/EBPalpha,beta consensus binding site between the bases -252 and -175 is important for the glucocorticoid-induced SAA1 gene expression in HASMCs but not in HepG2 cells
12077270
The endogenous SAA1 gene has a cytokine-driven transcriptional disadvantage compared to SAA2 that is superseded by a marginal transcriptional advantage when glucocorticoids are present.
12056504
relation to cholesterol metabolism and cardiovascular disease (REVIEW)
11830469
human platelets specifically adhere to SAA in an RGD- and alphaIIbbeta3-dependent manner, indicating a role for SAA in modulating platelet adhesion
Pathway: Selenium Pathway
(database: Wikipathways)
Pathway: Vitamin B12 Metabolism
(database: Wikipathways)
Pathway: Folate Metabolism
(database: Wikipathways)
Pathway: TRIF-mediated TLR3/TLR4 signaling
(database: Reactome)
Pathway: MyD88-independent cascade
(database: Reactome)
Pathway: Activated TLR4 signalling
(database: Reactome)
Pathway: Toll Like Receptor 4 (TLR4) Cascade
(database: Reactome)
Pathway: Scavenging by Class B Receptors
(database: Reactome)
Pathway: Toll Like Receptor 9 (TLR9) Cascade
(database: Reactome)
Pathway: MyD88 cascade initiated on plasma membrane
(database: Reactome)
Pathway: Toll Like Receptor 10 (TLR10) Cascade
(database: Reactome)
Pathway: Toll Like Receptor 3 (TLR3) Cascade
(database: Reactome)
Pathway: Toll Like Receptor 5 (TLR5) Cascade
(database: Reactome)
Pathway: TRAF6 Mediated Induction of proinflammatory cytokines
(database: Reactome)
Pathway: Toll Like Receptor 7/8 (TLR7/8) Cascade
(database: Reactome)
Pathway: Formyl peptide receptors bind formyl peptides and many other ligands
(database: Reactome)
Pathway: Peptide ligand-binding receptors
(database: Reactome)
Pathway: Toll-Like Receptors Cascades
(database: Reactome)
Pathway: TRAF6 mediated NF-kB activation
(database: Reactome)
Pathway: GPCR ligand binding
(database: Reactome)
Pathway: DEx/H-box helicases activate type I IFN and inflammatory cytokines production
(database: Reactome)
Pathway: Cytosolic sensors of pathogen-associated DNA
(database: Reactome)
Pathway: Toll Like Receptor 2 (TLR2) Cascade
(database: Reactome)
Pathway: Innate Immune System
(database: Reactome)
Pathway: ZBP1(DAI) mediated induction of type I IFNs
(database: Reactome)
Pathway: MyD88:Mal cascade initiated on plasma membrane
(database: Reactome)
Pathway: Toll Like Receptor TLR1:TLR2 Cascade
(database: Reactome)
Pathway: Toll Like Receptor TLR6:TLR2 Cascade
(database: Reactome)
Pathway: Immune System
(database: Reactome)
Pathway: G alpha (q) signalling events
(database: Reactome)
Pathway: Signal Transduction
(database: Reactome)
Pathway: Gastrin-CREB signalling pathway via PKC and MAPK
(database: Reactome)
Pathway: GPCR downstream signaling
(database: Reactome)
Pathway: RIP-mediated NFkB activation via ZBP1
(database: Reactome)
Pathway: TAK1 activates NFkB by phosphorylation and activation of IKKs complex
(database: Reactome)
Pathway: G alpha (i) signalling events
(database: Reactome)
Pathway: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
(database: Reactome)
Pathway: MyD88 dependent cascade initiated on endosome
(database: Reactome)
Pathway: Class A/1 (Rhodopsin-like receptors)
(database: Reactome)
Pathway: Advanced glycosylation endproduct receptor signaling
(database: Reactome)
Pathway: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
(database: Reactome)
Pathway: Endogenous TLR signaling
(database: PID)
Pathway: Binding and Uptake of Ligands by Scavenger Receptors
(database: Reactome)
Pathway: Signaling by GPCR
(database: Reactome)
Protein: SAA1 (P0DJI8)
Serum amyloid A-1 protein;
GO: 0001664
G-protein coupled receptor binding
GO: 0005576
extracellular region
GO: 0006953
acute-phase response
GO: 0007204
positive regulation of cytosolic calcium ion concentration
GO: 0030168
platelet activation
GO: 0030593
neutrophil chemotaxis
GO: 0034364
high-density lipoprotein particle
GO: 0045087
innate immune response
GO: 0045785
positive regulation of cell adhesion
GO: 0048246
macrophage chemotaxis
GO: 0048247
lymphocyte chemotaxis
GO: 0050708
regulation of protein secretion
GO: 0050715
positive regulation of cytokine secretion
GO: 0050716
positive regulation of interleukin-1 secretion
GO: 0050728
negative regulation of inflammatory response
GO: 0070062
extracellular vesicular exosome
GO: 0071682
endocytic vesicle lumen
KO: K17310
serum amyloid A protein
OMIM: 104750 SERUM AMYLOID A1; SAA1
Distance to locus: 40098
Gene: 144106 (ST13P5)
LD R2 of rs2403254 with intragenic SNP rs10832913: 0.40783
Chr 11
18283432-18285048 (+)
Distance to locus: -54925
LD R2 of rs2403254 with intragenic SNP rs1520886: 0.024498
Gene: 100528017 (SAA2-SAA4)
Chr 11
18252902-18270221 (-)
Distance to locus: -54925
LD R2 of rs2403254 with intragenic SNP rs1520886: 0.024498
Gene: 6289 (SAA2)
Chr 11
18259780-18270221 (-)
23223242
Pathogenic serum amyloid A 1.1 shows a long oligomer-rich fibrillation lag phase contrary to the highly amyloidogenic non-pathogenic SAA2.2
22300576
successful quantification of SAA2 in crude serum by MRM, for the first time, shows that SAA2 can be a good biomarker for the detection of lung cancers.
21103356
Data show that both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects.
20379614
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
18385816
CRP and SAA strongly correlated up to the fifth day of observation but were not good predictors of mortality in septic shock.
16737350
Increased expression of SAA2 by adipocytes in obesity may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities.
15170927
SAA1a/a genotype is one genetic factor that confers a significant risk for amyloidosis in the Turkish FMF population but neither SAA1 nor SAA2 genotypes had a significant effect on SAA level.
14871291
saa2 is regulated by tumor necrosis factor-alpha, interleukin-6, and glucocorticoids in hepatic and epithelial cells.
12077270
The glucocorticoid response element of the SAA2 promoter is dysfunctional compared to that of SAA1, hence glucocorticoids are unable to enhance the cytokine-driven transcriptional activity of SAA2.
Pathway: Selenium Pathway
(database: Wikipathways)
Pathway: Vitamin B12 Metabolism
(database: Wikipathways)
Pathway: Folate Metabolism
(database: Wikipathways)
Pathway: TRIF-mediated TLR3/TLR4 signaling
(database: Reactome)
Pathway: MyD88-independent cascade
(database: Reactome)
Pathway: Activated TLR4 signalling
(database: Reactome)
Pathway: Toll Like Receptor 4 (TLR4) Cascade
(database: Reactome)
Pathway: Scavenging by Class B Receptors
(database: Reactome)
Pathway: Toll Like Receptor 9 (TLR9) Cascade
(database: Reactome)
Pathway: MyD88 cascade initiated on plasma membrane
(database: Reactome)
Pathway: Toll Like Receptor 10 (TLR10) Cascade
(database: Reactome)
Pathway: Toll Like Receptor 3 (TLR3) Cascade
(database: Reactome)
Pathway: Toll Like Receptor 5 (TLR5) Cascade
(database: Reactome)
Pathway: TRAF6 Mediated Induction of proinflammatory cytokines
(database: Reactome)
Pathway: Toll Like Receptor 7/8 (TLR7/8) Cascade
(database: Reactome)
Pathway: Formyl peptide receptors bind formyl peptides and many other ligands
(database: Reactome)
Pathway: Peptide ligand-binding receptors
(database: Reactome)
Pathway: Toll-Like Receptors Cascades
(database: Reactome)
Pathway: TRAF6 mediated NF-kB activation
(database: Reactome)
Pathway: GPCR ligand binding
(database: Reactome)
Pathway: DEx/H-box helicases activate type I IFN and inflammatory cytokines production
(database: Reactome)
Pathway: Cytosolic sensors of pathogen-associated DNA
(database: Reactome)
Pathway: Toll Like Receptor 2 (TLR2) Cascade
(database: Reactome)
Pathway: Innate Immune System
(database: Reactome)
Pathway: ZBP1(DAI) mediated induction of type I IFNs
(database: Reactome)
Pathway: MyD88:Mal cascade initiated on plasma membrane
(database: Reactome)
Pathway: Toll Like Receptor TLR1:TLR2 Cascade
(database: Reactome)
Pathway: Toll Like Receptor TLR6:TLR2 Cascade
(database: Reactome)
Pathway: Immune System
(database: Reactome)
Pathway: G alpha (q) signalling events
(database: Reactome)
Pathway: Signal Transduction
(database: Reactome)
Pathway: Gastrin-CREB signalling pathway via PKC and MAPK
(database: Reactome)
Pathway: GPCR downstream signaling
(database: Reactome)
Pathway: RIP-mediated NFkB activation via ZBP1
(database: Reactome)
Pathway: TAK1 activates NFkB by phosphorylation and activation of IKKs complex
(database: Reactome)
Pathway: G alpha (i) signalling events
(database: Reactome)
Pathway: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
(database: Reactome)
Pathway: MyD88 dependent cascade initiated on endosome
(database: Reactome)
Pathway: Class A/1 (Rhodopsin-like receptors)
(database: Reactome)
Pathway: Advanced glycosylation endproduct receptor signaling
(database: Reactome)
Pathway: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
(database: Reactome)
Pathway: Endogenous TLR signaling
(database: PID)
Pathway: Binding and Uptake of Ligands by Scavenger Receptors
(database: Reactome)
Pathway: Signaling by GPCR
(database: Reactome)
Protein: SAA2 (P0DJI9)
Serum amyloid A-2 protein;
GO: 0006953
acute-phase response
GO: 0034364
high-density lipoprotein particle
KO: K17310
serum amyloid A protein
OMIM: 104751 SERUM AMYLOID A2; SAA2
Distance to locus: -66762
LD R2 of rs2403254 with intragenic SNP rs2460827: 0.010826
Gene: 6291 (SAA4)
Chr 11
18252902-18258384 (-)
20536400
studies provide the first evidence for a novel type of AA amyloidosis in which the fibrils were formed from a mutated SAA4 protein
12410800
The sequences of 1478 and 1836 bp of the SAA1 and SAA4 5'-flanking regions were determined.
Pathway: Selenium Pathway
(database: Wikipathways)
Pathway: Vitamin B12 Metabolism
(database: Wikipathways)
Pathway: Folate Metabolism
(database: Wikipathways)
Protein: SAA4 (P35542)
Serum amyloid A-4 protein;
GO: 0005576
extracellular region
GO: 0006953
acute-phase response
GO: 0034364
high-density lipoprotein particle
KO: K17310
serum amyloid A protein
OMIM: 104752 SERUM AMYLOID A4; SAA4
Distance to locus: -84188
Gene: 100423016 (MIR3159)
Chr 11
18409334-18409407
(+)
Distance to locus: 90021
LD R2 of rs2403254 with intragenic SNP rs2468790: 0.017585
Gene: 494141 (LOC494141)
Chr 11
18230685-18235125 (+)
Distance to locus: -90790
LD R2 of rs2403254 with intragenic SNP rs3758683: 0.11936
Gene: 3939 (LDHA)
Chr 11
18415936-18429765 (+)
23516535
the role played by ERRalpha in the regulation of lactate dehydrogenases A and B
23404405
Lactate dehydrogenase A is overexpressed in pancreatic cancer.
23266049
Data indicate that serum lactic dehydrogenase (S-LDH) appears to be a significant independent prognostic index in patients with metastatic nasopharyngeal carcinoma (NPC).
23184277
Increased LDH5 expression is associated with lymph node metastasis in oral squamous cell carcinoma.
23166385
Elevated lactate dehydrogenase level is associated with recurrent or refractory aggressive lymphoma.
22961700
LDHA plays an important role in the progression of esophageal squamous cell carcinoma by modulating cell growth
22948140
Cells expressing either PDK1 or LDHA maintained a lower mitochondrial membrane potential and decreased reactive oxygen species production with or without exposure to toxins.
22923663
Lactic acid induces myofibroblast differentiation via pH-dependent activation of transforming growth factor beta.
22897481
Studies indicate the mechanisms by which lactate dehydrogenase A (LDHA) promotes tumor growth and metastasis.
22593701
Data suggest that serum lactate dehydrogenase (LDH) kinetics might reflect disease behaviour in extracranial metastatic and primary sites without need for comprehensive imaging studies and is a quite inexpensive diagnostic test.
22429998
We demonstrate that LDH-A reduction can suppress the tumorigenicity of intestinal-type gastric cancer (ITGC) cells by downregulating Oct4 both in vitro and in vivo.
22360420
A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration.
22127970
Case Report: describe an elderly patient with physical therapy-induced rhabdomyolysis complicated by acute kidney injury associated with reduced skeletal muscle LDH-A activity.
21969607
LDH-A is tyrosine phosphorylated and activated by FGFR1 in cancer cells.
21858537
Results show that S-100B, MIA and LDH levels were significantly higher in patients with advanced melanoma than in disease-free patients or healthy controls.
21632858
Serum LDH and tissue LDH5 levels are complementary features that help to characterize the activity of LDH in colorectal cancer and have a potent value in predicting response to chemotherapy.
21452021
LDH-A reduction resulted in an inhibited cancer cell proliferation, elevated intracellular oxidative stress, and induction of mitochondrial pathway apoptosis.
21249322
High LDH is associated with M1b prostate cancer.
20951115
Presented are QM/MM calculations that show differences in geometries of active sites of M(4) and H(4) isoforms of human LDH ligated with oxamate, pyruvate or L-lactate.
20828817
High lactate dehydrogenase is associated with acute adult T-cell leukemia/lymphoma.
20385008
LDH5 is overexpressed in non-small cell lung cancer and could serve as a marker for malignancy. LDH5 correlates positively with the prognostic marker transketolase like 1 protein.
19923867
LDH5 is highly expressed in squamous cell head and neck cancer and is linked with local relapse, survival and distant metastasis.
19847924
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19838163
Correlation of LDH-5 expression with clinicopathological factors and with the expression of Bcl-2, Bcl-XL, Mcl-1 and GRP78 was examined in pigmented lesions, including nevi and melanoma at different stages of progression
19668225
ErbB2 promotes glycolysis at least partially through the HSF1-mediated upregulation of LDH-A.
19276158
LDH-A knockdown in the background of FH knockdown results in significant reduction in tumor growth in a xenograft mouse model.
19021062
LDH5 is highly upregulated in B-cell non-Hodgkin lymphomas and is in direct relation to factor HIF1alpha and HIF2alpha expression. LDH5 expression is linked with activated VEGFR2/KDR expression in both lymphoid lesions.
18821170
The expression of LDH and its isoenzymes in pleural effusions reflects the host reaction in pleural space and, in non-small-cell lung cancer, may also feature the anaerobic phenotype of cancer cells.
18814027
Modulation of LDH expression involves alpha6beta4 integrin-FAK-p38MAPK pathway.
18534967
LDL-M is released into blood fo patients exposed to myocardial ischemia reperfusion.
18521687
The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.
17483170
biophysical study of ligand binding and protein dynamics in lactate dehydrogenase
17178662
LDH1 was decreased in essential thrombocythemia. This isoenzymatic pattern could be expression of a metabolic adaptation.
17178662
LDH5 was reduced in idiopathic myelofibrosis. This isoenzymatic pattern could be expression of a metabolic adaptation [LDH5]
16766262
Reduction in LDH-A activity resulted in stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential.The tumorigenicity of the LDH-A-deficient cells was severely diminished.
16132575
Lactate dehydrogenase 5 content in tumor cells is directly related to an up-regulated hypoxia inducible factor pathway and is linked with an aggressive phenotype in colorectal adenocarcinomas.
15240094
These data indicate that LDH-A is induced through a non-genomic pathway of estrogen action.
12712614
The activity of this enzyme was studied in tissues, erythrocytes, and blood plasma of patients with peptic ulcer both in its uncomplicated course and in the development of complications.
12629811
The study of this protein in a sportsman is significant for assessment of training efficiency.
12555229
an LDHA exon5 haplotype confers increased risk for paradoxically decreased minute volume respiratory response to CO2 challenge but not to panic disorder
Pathway: Pyruvate metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human)
(database: KEGG)
Pathway: Propanoate metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: HIF-1 signaling pathway - Homo sapiens (human)
(database: KEGG)
Pathway: Cysteine and methionine metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Cori Cycle
(database: Wikipathways)
Pathway: Glycolysis and Gluconeogenesis
(database: Wikipathways)
Pathway: hypoxia-inducible factor in the cardivascular system
(database: BioCarta)
Pathway: TCR
(database: NetPath)
Pathway: Pyruvate metabolism
(database: Reactome)
Pathway: Validated targets of C-MYC transcriptional activation
(database: PID)
Pathway: Pyruvate metabolism and Citric Acid (TCA) cycle
(database: Reactome)
Pathway: The citric acid (TCA) cycle and respiratory electron transport
(database: Reactome)
Pathway: Methionine Cysteine metabolism
(database: INOH)
Pathway: Propanoate metabolism
(database: INOH)
Pathway: Glycolysis Gluconeogenesis
(database: INOH)
Pathway: EGFR1
(database: NetPath)
Pathway: Pyruvate metabolism
(database: INOH)
Pathway: pyruvate fermentation to lactate
(database: HumanCyc)
Pathway: HIF-1-alpha transcription factor network
(database: PID)
Pathway: hypoxia-inducible factor in the cardivascular system
(database: PID)
Protein: LDHA (P00338)
L-lactate dehydrogenase A chain;
EC: 1.1.1.27
L-lactate dehydrogenase.
(S)-lactate + NAD(+) = pyruvate + NADH.
GO: 0004459
L-lactate dehydrogenase activity
GO: 0005515
protein binding
GO: 0005634
nucleus
GO: 0005739
mitochondrion
GO: 0005829
cytosol
GO: 0005929
cilium
GO: 0006090
pyruvate metabolic process
GO: 0006096
glycolytic process
GO: 0021762
substantia nigra development
GO: 0031668
cellular response to extracellular stimulus
GO: 0044237
cellular metabolic process
GO: 0044281
small molecule metabolic process
GO: 0070062
extracellular vesicular exosome
KO: K00016
L-lactate dehydrogenase [EC:1.1.1.27]
ReactionKEGG: R00703
(S)-Lactate + NAD+ <=> Pyruvate + NADH + H+
ReactionKEGG: R01000
2-Hydroxybutanoic acid + NAD+ <=> 2-Oxobutanoate + NADH + H+
ReactionKEGG: R03104
3-Mercaptolactate + NAD+ <=> Mercaptopyruvate + NADH + H+
OMIM: 150000 LACTATE DEHYDROGENASE A; LDHA
OMIM: 612933 GLYCOGEN STORAGE DISEASE XI; GSD11
Distance to locus: 106254
LD R2 of rs2403254 with intragenic SNP rs2460832: 0.015713
Gene: 645319 (LOC645319)
Chr 11
18218207-18218892 (+)
Distance to locus: -108707
LD R2 of rs2403254 with intragenic SNP rs7938942: 0.089432
Gene: 3948 (LDHC)
Chr 11
18433853-18472793 (+)
21858537
Results show that S-100B, MIA and LDH levels were significantly higher in patients with advanced melanoma than in disease-free patients or healthy controls.
20499337
Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency.
18930904
hLdhc expression in cancer cells was regulated by transcription factor Sp1 and CREB and promoter CGI methylation
17935709
LDH3 is a supporting diagnostic marker in cases of chronic tuberculosis.
17178662
LDH3 was increased in essential thrombocythemia. This isoenzymatic pattern could be expression of a metabolic adaptation.
Pathway: Pyruvate metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human)
(database: KEGG)
Pathway: Propanoate metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Cysteine and methionine metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Glycolysis and Gluconeogenesis
(database: Wikipathways)
Pathway: Methionine Cysteine metabolism
(database: INOH)
Pathway: Propanoate metabolism
(database: INOH)
Pathway: Glycolysis Gluconeogenesis
(database: INOH)
Pathway: Pyruvate metabolism
(database: INOH)
Pathway: pyruvate fermentation to lactate
(database: HumanCyc)
Protein: LDHC (P07864)
L-lactate dehydrogenase C chain;
EC: 1.1.1.27
L-lactate dehydrogenase.
(S)-lactate + NAD(+) = pyruvate + NADH.
GO: 0004459
L-lactate dehydrogenase activity
GO: 0005634
nucleus
GO: 0005737
cytoplasm
GO: 0006096
glycolytic process
GO: 0006754
ATP biosynthetic process
GO: 0019244
lactate biosynthetic process from pyruvate
GO: 0019516
lactate oxidation
GO: 0030317
sperm motility
GO: 0031514
motile cilium
KO: K00016
L-lactate dehydrogenase [EC:1.1.1.27]
ReactionKEGG: R00703
(S)-Lactate + NAD+ <=> Pyruvate + NADH + H+
ReactionKEGG: R01000
2-Hydroxybutanoic acid + NAD+ <=> 2-Oxobutanoate + NADH + H+
ReactionKEGG: R03104
3-Mercaptolactate + NAD+ <=> Mercaptopyruvate + NADH + H+
OMIM: 150150 LACTATE DEHYDROGENASE C; LDHC
Distance to locus: 112361
LD R2 of rs2403254 with intragenic SNP rs4417246: 0.00024131
Gene: 645312 (GLTPP1)
Chr 11
18210451-18212785 (+)
18261224
The intronless GLTP gene at 11p15.1 was transcriptionally silent, primate-specific, and yielded inactive protein. A 5-exon/4-intron GLTP gene at 12q24.11 was the highly conserved, transcript source of active GLTP in human and vertebrate cells.
Distance to locus: 129319
LD R2 of rs2403254 with intragenic SNP rs2445180: 0.017123
Gene: 117196 (MRGPRX4)
Chr 11
18194384-18195827 (+)
20379614
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Protein: MRGX4 (Q96LA9)
Mas-related G-protein coupled receptor member X4;
GO: 0004930
G-protein coupled receptor activity
GO: 0005886
plasma membrane
GO: 0016021
integral component of membrane
KO: K08396
Mas-related G protein-coupled receptor member X
OMIM: 607230 MAS-RELATED G PROTEIN-COUPLED RECEPTOR FAMILY, MEMBER X4; MRGPRX4
Distance to locus: 149345
LD R2 of rs2403254 with intragenic SNP rs2445197: 0.014786
Gene: 645297 (LOC645297)
Chr 11
18174824-18175801 (+)
Distance to locus: -152228
LD R2 of rs2403254 with intragenic SNP rs11024671: 0.12694
Gene: 160287 (LDHAL6A)
Chr 11
18477374-18501147 (+)
18351441
expression of LDHAL6A was able to activate transcriptional activities of AP1(PMA)
Pathway: Pyruvate metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human)
(database: KEGG)
Pathway: Propanoate metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Cysteine and methionine metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Beta-mercaptolactate-cysteine disulfiduria
(database: SMPDB)
Pathway: Pyruvate Dehydrogenase Complex Deficiency
(database: SMPDB)
Pathway: Primary hyperoxaluria II, PH2
(database: SMPDB)
Pathway: Pyruvate kinase deficiency
(database: SMPDB)
Pathway: Gluconeogenesis
(database: SMPDB)
Pathway: Leigh Syndrome
(database: SMPDB)
Pathway: Glycogenosis, Type IA. Von gierke disease
(database: SMPDB)
Pathway: Glycogenosis, Type IC
(database: SMPDB)
Pathway: Cysteine Metabolism
(database: SMPDB)
Pathway: Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease
(database: SMPDB)
Pathway: Pyruvate Metabolism
(database: SMPDB)
Pathway: Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency)
(database: SMPDB)
Pathway: Triosephosphate isomerase
(database: SMPDB)
Pathway: Fructose-1,6-diphosphatase deficiency
(database: SMPDB)
Pathway: Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1)
(database: SMPDB)
Pathway: Glycogenosis, Type IB
(database: SMPDB)
Pathway: pyruvate fermentation to lactate
(database: HumanCyc)
Protein: LDH6A (Q6ZMR3)
L-lactate dehydrogenase A-like 6A;
EC: 1.1.1.27
L-lactate dehydrogenase.
(S)-lactate + NAD(+) = pyruvate + NADH.
GO: 0004459
L-lactate dehydrogenase activity
GO: 0005737
cytoplasm
GO: 0006096
glycolytic process
KO: K00016
L-lactate dehydrogenase [EC:1.1.1.27]
ReactionKEGG: R00703
(S)-Lactate + NAD+ <=> Pyruvate + NADH + H+
ReactionKEGG: R01000
2-Hydroxybutanoic acid + NAD+ <=> 2-Oxobutanoate + NADH + H+
ReactionKEGG: R03104
3-Mercaptolactate + NAD+ <=> Mercaptopyruvate + NADH + H+
Distance to locus: 165119
LD R2 of rs2403254 with intragenic SNP rs4619132: 0.044144
Gene: 117195 (MRGPRX3)
Chr 11
18142502-18160027 (+)
15809047
overexpression of the human MrgX3 gene causes a disturbance of the normal cell-differentiation process
Protein: MRGX3 (Q96LB0)
Mas-related G-protein coupled receptor member X3;
GO: 0004930
G-protein coupled receptor activity
GO: 0005886
plasma membrane
GO: 0016021
integral component of membrane
KO: K08396
Mas-related G protein-coupled receptor member X
OMIM: 607229 MAS-RELATED G PROTEIN-COUPLED RECEPTOR FAMILY, MEMBER X3; MRGPRX3
Distance to locus: 176712
LD R2 of rs2403254 with intragenic SNP rs11024688: 0.11217
Gene: 7251 (TSG101)
Chr 11
18501858-18548503 (-)
23408603
These results support a model in which both HIV-1 Gag-induced membrane curvature and Gag-ESCRT interactions promote tetherin recruitment, but the recruitment level achieved by the former is sufficient for full restriction.
23217182
Data indicate tht n the Biaka, strong signal of selection was detected at CUL5 and at TSG101.
22768867
The expression of TSG101 in HCC is higher than that in corresponding non-cancer tissues and the expression level is closely correlated with TNM stage and metastasis of HCC.
22675076
The results provide evidence for a two-step splicing pathway of the TSG101 mRNA in which the initial constitutive splicing removes all 14 authentic splice sites, thereby bringing the weak alternative splice sites into close proximity.
22348143
identified TSG101 as a novel FIP4-binding protein, which can also bind FIP3. alpha-helical coiled-coil regions of both TSG101 and FIP4 mediate the interaction with the cognate protein
21880841
Depletion of endogenous Tsg101 by siRNA led to a significant reduction of HEV release in cultured cells.
21528537
HIV-1 infection affects the expression of host factors TSG101 and Alix
21455631
Overexpression of PEG10 and TSG101 was detected in gallbladder adenocarcinoma.
21117030
TSG101 knockdown in breast cancer cells induces apoptosis and inhibits proliferation. TSG101 may play a biological role through modulation of the MAPK/ERK signaling pathway in breast cancer.
20504928
Taken together, these data indicate that Marburg virus nucleoprotein enhances budding of virus-like particles by recruiting Tsg101 to the VP40-positive budding site through a PSAP late-domain motif.
20399684
show that ubiquitin recognition by TSG101 is required for cSMAC formation, T cell receptor (TCR) microcluster signal termination, TCR downregulation.
20372822
Results suggest that TSG101 down-regulation in cervical cancer cells is not regulated by genetic or epigenetic events.
19787439
TSG101 may induce the malignant phenotype of cells.
19692479
Data suggest that HSV-1 production is independent of ALIX and TSG101 expression.
19520058
Ca2+-loaded ALG-2 bridges Alix and TSG101 as an adaptor protein.
19362095
molecular dynamics simulations study of the association of the ubiquitin E2 variant domain of the protein Tsg101 and an HIV-derived nonapeptide
19282983
Nucleocapsid region of Gag cooperates with PTAP in the recruitment of cellular proteins necessary for its L domain activity and binds the Bro1-CHMP4 complex required for LYPX(n)L-mediated budding.
19143632
[review]
18600204
Persistent upregulation in colorectal carcinoma cases studied.
18367816
study found that not only the PTAP sequence in the GAT domain but also the PSAP sequence in the C-terminal region of Tom1L1 is responsible for its interaction with the UEV domain of Tsg101 and competes with the HIV-1 Gag protein for the Tsg101 interaction
18077552
Tal polyubiquitinates lysine residues in the C-terminus of uncomplexed Tsg101, resulting in proteasomal degradation.
17940959
Ebola virus can use vacuolar protein surting proteins independently of TSG101 for budding and reveal vacuolar sorting protein 4 as a potential target for filovirus therapeutics.
17853893
that ALIX and TSG101/ESCRT-I also bind a series of proteins involved in cytokinesis, including CEP55, CD2AP, ROCK1, and IQGAP1.
17606716
TSG101 negatively regulates p21 levels, and up-regulation of TSG101 is associated with poor prognosis in ovarian cancer
17556548
study shows that two proteins involved in HIV-1 budding-Tsg101, a subunit of the endosomal sorting complex required for transport I (ESCRT-I), & Alix, an ESCRT-associated protein-were recruited to the midbody during cytokinesis by interaction with Cep55
17428861
ALIX can have a dramatic effect on HIV-1 release by binding at the CHMP4B site; the ability to use ALIX may allow HIV-1 to replicate in cells that express only low levels of Tsg101
17369844
the Tsg101 protein has only weak oncogenic properties
17321722
These data suggest that an intracellular calcium store independent PKC-Sp1 signaling pathway induces early keratinocyte differentiation through upregulation of TSG101.
17229889
TSG101 is a specific Mahogunin substrate
17182691
role for TSG101 in the replication of EBV, a DNA virus, that differs from what is observed for RNA viruses, where TSG101 aids mainly in the endosomal sorting of enveloped late viral proteins for assembly at the plasma membrane
17110434
These results demonstrate that TSG101 is important for CITED2- and HIF-1alpha-mediated cellular regulation in ovarian carcinomas.
17060450
analysis of mechanism of formation of the principal MDM2 isoforms, differential effects of p53 on the production of these isoforms, and differential abilities of human MDM2 isoforms as regulators of the MDM2/TSG101 and p53/MDM2 feedback control loops
17014699
Four proteins (TSG101,Hrs,Aip1/Alix, and Vps4B) of the ESCRT (endosomal sorting complex required for transport) machinery were localized in T cells and macrophages by quantitative electron microscopy.
16707569
These results indicate that Tsg101 is required for the formation of stable vacuolar domains within the early endosome that develop into multivesicular body (MVBs) and Hrs is required for the accumulation of internal vesicles within MVBs.
16552148
The crystal structure of the TSG101 UEV domain (TSG101-UEV) is presented.
16407257
the ORF3 protein exploits the endosomal sorting machinery to enhance the secretion of an immunosuppressant molecule (alpha1 microglobulin) from cultured hepatocytes
16256744
The Tsg101 proteins function in endosomal sorting and are required to incorporate late endosomes into multivesicular bodies.
16138902
Data suggest that RSV and HIV-1 Gag direct particle release through independent ESCRT-mediated pathways that are linked through Tsg101-Nedd4 interaction.
16004603
The expression and transport of ALG-2 in association with TSG101 and Vps4B are reported.
15908698
interaction of Gag with Tsg101 and Alix favors budding from the plasma membrane and relieves a requirement for ubiquitination by Nedd4
15657031
TSG101 binds GR and protects the non-phosphorylated receptor from degradation.
15126635
Tsg101 and Nedd4.1 act successively in the assembly process of HTLV-1 to ensure proper Gag trafficking through the endocytic pathway up to late endosomes where the late steps of retroviral release occur.
15053872
X-ray crystallography study of the UEV domain of TSG101 and ubquitin showed the basis for the binding recognition at high resolution.
15033475
molecular interactions between Daxx and TSG101 establish an efficient repressive transcription complex in the nucleus
14991575
Reduction of TSG101 protein has a negative impact on breast and prostate tumor cell growth
14761944
TSG101 activates androgen receptor-induced transcription by transient stabilization of the monoubiquitinated state
14526201
alternative splicing and role implicated in interaction with HIV-1
12802020
the TSG101 interaction with HRS is a crucial step in endocytic down-regulation of mitogenic signaling and this interaction may have a role in linking the functions of early and late endosomes
12743307
truncated and full length forms of TSG101 inhibit HIV-1 budding by interacting with the p6 L domain and by disrupting the cellular endosomal sorting machinery
12725919
Human ortholog TSG101 does not substitute VPS23 in its ability to rescue the phenotype of defective plasma membrane proteins
12505256
Analysis of BRCA1, TP53, and TSG101 germline mutations in German breast and/or ovarian cancer families.
12388682
interacts specifically with human immunodeficiency virus type 2 gag polyprotein, results in increased levels of ubiquinated gag, and is incorporated into HIV-2 virions
12379843
solution structure of the UEV (ubiquitin E2 variant) binding domain of Tsg101 in complex with a PTAP peptide that spans the late domain of HIV-1 p6(Gag)
12006492
structure and functional interactions of its binding sites
11943869
Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1).
11916981
recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates.
11838966
TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins.
Pathway: Endocytosis - Homo sapiens (human)
(database: KEGG)
Pathway: Internalization of ErbB1
(database: PID)
Pathway: HIV Life Cycle
(database: Reactome)
Pathway: HIV Infection
(database: Reactome)
Pathway: Disease
(database: Reactome)
Pathway: TCR
(database: NetPath)
Pathway: Late Phase of HIV Life Cycle
(database: Reactome)
Pathway: Budding and maturation of HIV virion
(database: Reactome)
Pathway: Membrane binding and targetting of GAG proteins
(database: Reactome)
Pathway: Endosomal Sorting Complex Required For Transport (ESCRT)
(database: Reactome)
Pathway: Membrane Trafficking
(database: Reactome)
Protein: TS101 (Q99816)
Tumor susceptibility gene 101 protein;
GO: 0000813
ESCRT I complex
GO: 0001558
regulation of cell growth
GO: 0003677
DNA binding
GO: 0003714
transcription corepressor activity
GO: 0005515
protein binding
GO: 0005634
nucleus
GO: 0005737
cytoplasm
GO: 0005769
early endosome
GO: 0005770
late endosome
GO: 0005771
multivesicular body
GO: 0006464
cellular protein modification process
GO: 0007050
cell cycle arrest
GO: 0008285
negative regulation of cell proliferation
GO: 0010008
endosome membrane
GO: 0015031
protein transport
GO: 0016032
viral process
GO: 0016197
endosomal transport
GO: 0019058
viral life cycle
GO: 0019068
virion assembly
GO: 0019082
viral protein processing
GO: 0030216
keratinocyte differentiation
GO: 0031625
ubiquitin protein ligase binding
GO: 0031902
late endosome membrane
GO: 0043130
ubiquitin binding
GO: 0043162
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
GO: 0045892
negative regulation of transcription, DNA-templated
GO: 0046755
viral budding
GO: 0048306
calcium-dependent protein binding
GO: 0051301
cell division
GO: 0061024
membrane organization
GO: 0070062
extracellular vesicular exosome
GO: 0075733
intracellular transport of virus
KO: K12183
ESCRT-I complex subunit TSG101
OMIM: 601387 TUMOR SUSCEPTIBILITY GENE 101; TSG101
OMIM: 114480 BREAST CANCER
Distance to locus: 186640
Gene: 100422666 (LOC100422666)
Chr 11
18511786-18512501
(-)
Distance to locus: -187467
LD R2 of rs2403254 with intragenic SNP rs2468782: 0.044144
Gene: 6290 (SAA3P)
Chr 11
18134019-18137679 (-)
Pathway: Selenium Pathway
(database: Wikipathways)
Pathway: Vitamin B12 Metabolism
(database: Wikipathways)
Pathway: Folate Metabolism
(database: Wikipathways)
Distance to locus: 196753
LD R2 of rs2403254 with intragenic SNP rs871699: 0.048632
Gene: 100289300 (HIGD1AP5)
Chr 11
18122973-18128393 (+)
Distance to locus: -197508
LD R2 of rs2403254 with intragenic SNP rs3741199: 0.053612
Gene: 113174 (SAAL1)
Chr 11
18101890-18127638 (-)
22127701
Overexpression of SPACIA1/SAAL1, a newly identified gene that is involved in synoviocyte proliferation, accelerates the progression of synovitis in mice and humans.
Protein: SAAL1 (Q96ER3)
Protein SAAL1;
GO: 0005576
extracellular region
GO: 0006953
acute-phase response
Distance to locus: 228098
LD R2 of rs2403254 with intragenic SNP rs7119085: 0.11619
Gene: 55293 (UEVLD)
Chr 11
18553244-18610281 (-)
12427560
identification, sequencing and analysis of cDNA in various colon carcinoma cell lines as well as normal and tumor samples from colon
Protein: UEVLD (Q8IX04)
Ubiquitin-conjugating enzyme E2 variant 3;
GO: 0006464
cellular protein modification process
GO: 0015031
protein transport
GO: 0016616
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
GO: 0044262
cellular carbohydrate metabolic process
GO: 0070062
extracellular vesicular exosome
OMIM: 610985 UBIQUITIN E2 VARIANT AND LACTATE/MALATE DEHYDROGENASE DOMAINS-CONTAINING PROTEIN; UEVLD
Distance to locus: -262811
LD R2 of rs2403254 with intragenic SNP rs2056246: 0.04383
Gene: 7166 (TPH1)
Chr 11
18042084-18062335 (-)
23597148
Our results suggest that in acute depression TPH1 A218C polymorphism and specifically the CC genotype together with the information on remission or treatment response differentiates between different temperament profiles and their changes.
23328530
TPH1 deficiency or inhibition reduces allergic airway inflammation. Platelet-derived 5-HT is pivotal in AAI and lack of 5-HT leads to impaired Th2 priming capacity of bone marrow dendritic cells.
23177301
There is a relationship between sex, age & the TPH1 locus, with a trend towards a lower frequency of the AA genotype in former smokers. The TPH1 polymorphism is an indicator of therapeutic failure in smoking cessation.
23157339
This study detected allelic or genotypic associations of TPH1 in clinically significant depression in Alzheimer;s disease .
23088179
Associations between adolescents' physical activity and depressive symptoms are not modified by plasticity genes.
22781862
Among maltreated children, polymorphisms of TPH1 were related to heightened self-report and peer report of antisocial behavior.
22697203
Aggression in MDD patients is more susceptible to an excess of TPH1 CC homozygote than in undifferentiated somatoform disorder patients. TPH1 gene is most likely to have a shared effect on aggression and MDD.
22483952
variants in TPH1 gene constitute risk factors for post traumatic stress disorder symptoms.
22429480
The GGCCGGGC haplotype in the first haplotype block of TPH1 was significantly associated with middle insomnia.
22323131
In conclusion, regardless of visceral hypersensitivity state, several serotonergic signaling components are altered in IBS patients.
22053918
results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia.
21989108
Variation in TPH1 may increase risk for developing borderline personality disorder as a result of childhood abuse.
21836641
In non-diabetic controls, SNPs of TPH1 were associated with waist circumference and BMI.
21601290
The TPH1 A218C polymorphism is a potential biomarker for bipolar disorder and alcohol dependence risk in Caucasian population (Meta-Analtsis)
21308753
we concluded that TRH1 SNP is not associated with either adolescent idiopathic scoliosis predisposition or curve severity in Japanese.
21073637
Results describe associations of tryptophan hydroxylase 1 and 2 gene variants with irritable bowel syndrome-related GI symptoms and stool characteristics.
20945066
Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20945066
This study indicated that the TPH1 218A/C genotype and allele frequencies differed between Taiwanese healthy controls and patients with major depressive disorder
20921119
Family analysis of 38 TPH1 mutation carriers and 41 of their offspring revealed that offspring of mothers carrying TPH1 mutations reported 1.5- to 2.5-times-higher ADHD scores and related symptoms during childhood and as adults than did controls.
20580984
The results suggest that TPH1 gene variation participates in the regulation of serotonin and dopamine turnover rates in the central nervous system of healthy human subjects.
20213726
In the single largest attention-deficit/hyperactivity disorder (ADHD) genetic study of TPH1 and TPH2 variants presented to date (n = 3,559 individuals), evidence for a substantial effect of common genetic variants on persistent ADHD, was not found.
20213726
Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
20198979
Association between the tryptophan hydroxylase (TPH) gene polymorphic markers and endogenous psychoses
20144688
Neither common genetic variations of TPH1 nor TPH2 are likely to contribute to the genetic susceptibility to schizophrenia in Japanese population.
20046510
The findings suggest that TPH1 does not play a major role in aggressive behavior via anger in schizophrenic patients.
19961731
The TPH gene A218C polymorphism is not associated with essential hypertension in Chinese northern Han population.
19939457
Studies indicate that the mechanism of oxygen activation in tryptophan hydroxylase does not require inversion of spin.
19874868
In this Finnish population TPH1 218A/C polymorphism was associated with the risk of MDD and treatment response; CC genotype was associated with the increased risk of MDD and lower probability of responding treatment.
19816759
The catalytic domains of human tryptophan hydroxylase 1 and 2 have been expressed, purified and the kinetic properties have been studied and are compared.
19744316
Expression of DKK1 and TPH1 were negatively regulated by ASCL1 in pancreatic endocrine tumours.
19590397
evaluation of association of 7 serotonin signal transduction-linked SNP's [HTR1A (rs6295), HTR2A (rs6313, rs6311 & rs7997012), HTR6 (rs1805054), TPH1 (rs1800532) & TPH2 (rs1386494)] with major depressive disorder; no association found
19526457
Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
19526457
tryptophan hydroxylase 1 (TPH1) has a role in schizophrenia susceptibility and suicidal behavior
19506906
Meta-analysis of gene-disease association. (HuGE Navigator)
19500158
Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of amygdala activity in patients with MDD.
19474754
we found significant associations of bodyweight gain by more than 4 kg during antidepressant treatment with polymorphisms in genes coding for COMT and TPH1.
19445671
TPH1 were expressed in all brain regions similarly except for within the striatum and cerebellum, where TPH1 was expressed at a significantly higher level than TPH2.
19381154
TPH1 variation (rs10488683) was relevant in the diathesis for suicide attempts.
19233335
neuronal TPH1 & TPH2 expression in anterior pituitary; evidence against a strictly separated duality of serotonergic system; TPH1 may also have impact on neuronal mechanisms via hypothalamic-pituitary-adrenal axis regulation by its pituitary localization
19220488
TPH-1 genotype could confer a vulnerability to suicidal behaviour through a reduced capacity to control anger
19181488
In human no significant TPH1 expression was detected in the brain.
19095219
Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19077664
Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19052197
Hence, our study shows, for the first time, evidence of a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced anxiety relief.
19032713
Meta-analysis of gene-disease association. (HuGE Navigator)
18982004
Meta-analysis of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18937498
the chicken TPH1.Trp.imidazole structure resembles the PAH.BH 4.thienylalanine structure more (root-mean-square deviation for Calpha atoms of 0.90 A) than the human TPH1 structure (root-mean-square deviation of 1.47 A).
18826425
TPH-1 haplotype displayed a significantly higher frequency in patients with borderline personality disorder with impaired decision making
18813430
The effect of TPH gene polymorphism on TMD development and whether AA genotype or A allele are preventive factors for TMD remains unclear.
18794762
These results suggested that TPH1 was an adolescent idiopathic scoliosis predisposition gene.
18583979
Meta-analysis of gene-disease association. (HuGE Navigator)
18562131
792 cigarette smokers from the Patch in Practice trial were genotyped for the tryptophan hydroxylase (TPH1 A779C), serotonin transporter (SLC6A45-HTTLPR), and 5-HT1A (HTR1A C-1019G) polymorphisms.
18562131
Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
18506706
Results suggest that the A allele of the tryptophan hydroxylase-1 A218 polymorphism may be associated with Borderline Personality Disorder, and that it does not appear to be related to suicidal behavior in this population.
18402117
Polymorphism of the TPH gene-T457C locus could show ethnic and regional differences.
18366104
Three polymorphisms with theoretical and/or empirical ties to ASB or related traits (i.e., tryptophan hydroxylase-A218C, 5HT(2A) His452Tyr, and the DAT1 variable nucleotide tandem repeat) were genotyped.
18332644
The result suggests that 218A/C variants of TPH1 cannot play a major role as predictor of treatment response as well as intolerance in Japanese patients with major depression.
18221792
It is suggested that TPH1 protein may be implicated in schizophrenia with beta-thalassemia simultaneously, present on the short arm of chromosome 11.
18181017
Allele frequencies of three TPH2 variants and a TPH1 variant vary significantly among four ethnic groups with heroid adddiction.
18177948
TPH1 gene is implicated in depression.
17986837
TPH1 779A/C SNP is related to nicotine dependence and is associated with smoking status discriminating smokers from never-smokers and showed a tendency for an association with the degree of nicotine dependence.
17870198
Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
17870198
There were no significant associations between the polymorphisms or haplotypes of TPH1 and schizophrenia in our Japanese subjects. Our updated meta-analysis suggests the possible involvement of the TPH1 218A allele in schizophrenia.
17548152
These findings found that tryptophan-hydroxylase-1 A218C polymorphism does not play a part in the genetic susceptibility to bulimia nervosa, but to be involved in predisposing bulimic patients to a more disturbed eating behavior and higher harm avoidance.
17521439
TPH1 A779C C/A genotype was inversely associated with good treatment response to neuroleptics when compared with non-responding patients with schzophrenia
17509016
Results describe regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) receptors in the stomach and duodenum.
17221847
study reports the learning process of decision-making in suicide attempters to be modulated by four serotonergic gene polymorphisms, 5HTTLPR, TPH1 A218C, MAOA u-VNTR, and TPH2 rs1118997
17194593
Since it is unlikely that TPH polymorphism alters serotonin biosynthesis, its association with migraine may be attributed to linkage disequilibrium with a functional variant within the TPH gene or a nearby gene.
17066254
We studied the association between tryptophan hydroxylase 1 (TPH1) A218C polymorphism and treatment response in electroconvulsive therapy (ECT).
17026953
These findings do not support a major role for common 5-hydroxytryptamine transporter, TPH1, and monoamine oxidase A polymorphisms in contributing to susceptibility to premenstrual dysphoric disorder.
16958027
It appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including severe obsessive-compulsive behaviors and self-stimulatory behaviors.
16848783
The presence of the A/A haplotype of the TPH1 intron 7 polymorphism predicted a high level of adulthood harm avoidance in the presence of a hostile childhood environment. Findings also suggest a gene-environment correlation for novelty seeking in men.
16822601
polymorphisms play no significant roles in the pathogenesis and clinical symptomatologiy of panic dissorder in a Korean population.
16806098
Single marker association analyses showed two SNPs significantly associated with schizophrenia. A "sliding window" analysis attributed the strongest disease association to a haplotype configuration localized between the promoter region and intron 3.
16741719
Meta-analysis of gene-disease association. (HuGE Navigator)
16716203
A218C polymorphism of the TPH gene may not be a susceptibility factor for suicidal behavior in this group of psychiatric patients but confirm that a family suicidal behavior history increases the proband's suicide attempt risk.
16538180
The A218C SNP in TPH1 is not associated with completed suicide.
16467214
TPH1 may play a significant role in the aetiology of psychiatric disorders in the Han Chinese population.
16450114
Meta-analysis of gene-disease association. (HuGE Navigator)
16450114
Strong overall association between suicidal behavior and the A779C/A218C polymorphisms, supporting the involvement of TPH in the pathogenesis of suicidal behavior.
16389593
Haplotype analyses showed that the rare 218A/-6526G haplotype was significantly not transmitted to probands with Attention deficit hyperactivity disorder.
16389591
The TPH CC genotype in elderly victims of violent suicide points to the possible combined effect of the respective genetic factor and physiological changes during aging on the predisposition to this disorder.
16314762
A218C polymorphism of the TPH gene does not play a major role in pathogenesis in major depressive disorder and does not serve as a modulator of antidepressant activity.
16165107
te most common TPH-1 variants appear to carry no risk, while some of the less frequent variants might contribute to genetic predisposition to major depression
15799788
Single nucleotide polymorphisms in the tryptophan hydroxylase gene are not associated with bipolar affective disorder.
15722951
Tryptophan hydroxylasse polymorphisms not statistically diffrent in general anxiety disorder in Chinese.
15654285
Polymorphisms in the promoter region may influence the function of the TPH1 gene and further influence the proclivity of alcohol dependence in one ethnic group in Taiwan.
15635702
The positive heterosis effects with respect to nicotine addiction and personality support the idea that the TPH1 gene exerts pleiotropic effects.
15544576
Five single nucleoside polymorphisms of the TPH1 gene were studied in postpartum women with depression or/and anxiety. Genotype frequency differences for the T27224C polymorphism were found between the comorbid and normal groups.
15211625
There was a nearly doubling of the risk for childhood-onset schizophrenia associated with the AA genotype compared to other genotype groups in a Japanese sample
15182943
This study suggested that aggression in male subjects with Alzheimer's disease may be genetically linked to polymorphic variation at the tryptophan hydroxylase gene.
15135070
the denatured state properties of the AAAHs (TH, TPH and PAH) contribute significantly to the stability of these enzymes and their tolerance towards missense mutations
15052272
Clinical trial of gene-environment interaction and pharmacogenomic / toxicogenomic. (HuGE Navigator)
15052272
Study assessed genetic factors influencing antidepressant response to fluoxetine. Results implicate TPH1 in general response to fluoxetine.
14681922
Meta-analysis of gene-disease association. (HuGE Navigator)
14504413
Population-based association study tested the hypothesis that the tryptophan hydroxylase (TPH) A218C was associated with TPQ personality trait scores in a sample population of 209 young healthy Chinese.
12960746
Association of tryptophan hydroxylase gene polymorphisms and unipolar depression in a case-control study design.
12915291
Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
12476329
THis enzyme's immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls.
12379098
X-ray crystal structure analysis of a truncated functional form of TPH with the bound cofactor analogue 7,8-dihydro-L-biopterin provides the first atomic-resolution information for the catalytic domain and cofactor binding site of the enzyme.
12208565
Clinical trial of gene-environment interaction. (HuGE Navigator)
12116191
Meta-analysis of gene-disease association. (HuGE Navigator)
11992558
study did not support the involvement of 5-HTTLPR, TPH, MAO-A, or DRD4 polymorphisms in mood disorders
11747434
In a stable N-terminally truncated form of TPH that includes the catalytic domain, residue Phe-313 interacts with the substrate through ring stacking, thus predicting substrate specificity.
11597824
Clinical trial of gene-environment interaction. (HuGE Navigator)
11526473
Clinical trial of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator)
Pathway: Tryptophan metabolism - Homo sapiens (human)
(database: KEGG)
Pathway: Serotonergic synapse - Homo sapiens (human)
(database: KEGG)
Pathway: Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics
(database: PharmGKB)
Pathway: Tryptophan Metabolism
(database: SMPDB)
Pathway: Tryptophan metabolism
(database: Wikipathways)
Pathway: Biogenic Amine Synthesis
(database: Wikipathways)
Pathway: SIDS Susceptibility Pathways
(database: Wikipathways)
Pathway: Metabolism of amino acids and derivatives
(database: Reactome)
Pathway: Serotonin and melatonin biosynthesis
(database: Reactome)
Pathway: serotonin and melatonin biosynthesis
(database: HumanCyc)
Pathway: Tryptophan degradation
(database: INOH)
Pathway: tryptophan utilization I
(database: HumanCyc)
Pathway: tryptophan utilization II
(database: HumanCyc)
Pathway: Amine-derived hormones
(database: Reactome)
Protein: TPH1 (P17752)
Tryptophan 5-hydroxylase 1;
EC: 1.14.16.4
Tryptophan 5-monooxygenase.
L-tryptophan + tetrahydrobiopterin + O(2) = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin.
GO: 0004510
tryptophan 5-monooxygenase activity
GO: 0005506
iron ion binding
GO: 0005829
cytosol
GO: 0007623
circadian rhythm
GO: 0009072
aromatic amino acid family metabolic process
GO: 0016597
amino acid binding
GO: 0030279
negative regulation of ossification
GO: 0034641
cellular nitrogen compound metabolic process
GO: 0035902
response to immobilization stress
GO: 0042427
serotonin biosynthetic process
GO: 0043005
neuron projection
GO: 0044281
small molecule metabolic process
GO: 0046219
indolalkylamine biosynthetic process
GO: 0046849
bone remodeling
GO: 0060749
mammary gland alveolus development
KO: K00502
tryptophan 5-monooxygenase [EC:1.14.16.4]
ReactionKEGG: R01814
Tetrahydrobiopterin + L-Tryptophan + Oxygen <=> 5-Hydroxy-L-tryptophan + Dihydrobiopterin + H2O
ReactionKEGG: R07213
L-Tryptophan + Tetrahydrobiopterin + Oxygen <=> 5-Hydroxy-L-tryptophan + 4a-Hydroxytetrahydrobiopterin
OMIM: 191060 TRYPTOPHAN HYDROXYLASE 1; TPH1
Distance to locus: -290509
LD R2 of rs2403254 with intragenic SNP rs4402275: 0.097315
Gene: 26297 (SERGEF)
Chr 11
17809595-18034637 (-)
12459492
DelGEF binds to the human homologue of Sec5 and modulates secretion.
Protein: SRGEF (Q9UGK8)
Secretion-regulating guanine nucleotide exchange factor;
GO: 0005087
Ran guanyl-nucleotide exchange factor activity
GO: 0005515
protein binding
GO: 0005634
nucleus
GO: 0005737
cytoplasm
GO: 0007165
signal transduction
GO: 0032316
regulation of Ran GTPase activity
GO: 0050709
negative regulation of protein secretion
KO: K15421
secretion-regulating guanine nucleotide exchange factor
OMIM: 606051 SECRETION-REGULATING GUANINE NUCLEOTIDE EXCHANGE FACTOR; SERGEF
Distance to locus: 291855
LD R2 of rs2403254 with intragenic SNP rs6416020: 0.10506
Gene: 100129966 (LOC100129966)
Chr 11
18617001-18617913 (-)
Distance to locus: -296205
LD R2 of rs2403254 with intragenic SNP rs16935596: 0.1049
Gene: 100506540 (LOC100506540)
Chr 11
18621351-18631802 (+)
Distance to locus: 302802
Gene: 144108 (SPTY2D1)
LD R2 of rs2403254 with intragenic SNP rs16935596: 0.1049
Chr 11
18627948-18656020 (-)
Protein: SPT2 (Q68D10)
Protein SPT2 homolog;
KO: K15193
protein SPT2
Distance to locus: -361331
LD R2 of rs2403254 with intragenic SNP rs11024754: 0.092861
Gene: 100506569 (LOC100506569)
Chr 11
18686477-18688031 (+)
Distance to locus: -395205
LD R2 of rs2403254 with intragenic SNP rs14792: 0.024249
Gene: 144110 (TMEM86A)
Chr 11
18720351-18726332 (+)
Protein: TM86A (Q8N2M4)
Lysoplasmalogenase-like protein TMEM86A;
GO: 0016021
integral component of membrane
Distance to locus: 400706
LD R2 of rs2403254 with intragenic SNP rs1867877: 0.035306
Gene: 283284 (IGSF22)
Chr 11
18725852-18747777 (-)
Protein: IGS22 (Q8N9C0)
Immunoglobulin superfamily member 22;
Distance to locus: 424329
LD R2 of rs2403254 with intragenic SNP rs7950091: 0.10383
Gene: 84867 (PTPN5)
Chr 11
18749475-18813389 (-)
22885232
This experiments demonstrated that deletion of STEP can enhance experience-induced neuroplasticity and memory formation
22649233
This study identified a novel role for PTPN5 in mediating the development of stress-related cognitive and morphological changes.
22555153
The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contribute to aspects of the neuropathology of schizophrenia.
21883219
STEP(61kDa) is required for Abeta transgene-mediated internalization of GluA1/GluA2 glutamate receptors in a transgenic mousemodel.
20699650
STEP contributes to aspects of the pathophysiology in Alzheimer's disease; loss of GluN1/GluN2B subunits from neuronal membranes and Abeta-mediated NMDAR internalization are discussed
20427654
findings show that STEP(61) levels are progressively increased in the prefrontal cortex of Alzheimer disease brains
20379614
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19000305
in colorectal tumors, microsatellite repeats mutation rates are higher than the mean mutation frequency
16441242
determined high-resolution structures of all of the human family members of Mitogen-Activated Protein Kinase-specific protein tyrosine phosphatases
Pathway: MAPK signaling pathway - Homo sapiens (human)
(database: KEGG)
Pathway: MAPK Signaling Pathway
(database: Wikipathways)
Pathway: EGF-EGFR Signaling Pathway
(database: Wikipathways)
Protein: PTN5 (P54829)
Tyrosine-protein phosphatase non-receptor type 5;
EC: 3.1.3.48
Protein-tyrosine-phosphatase.
Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
GO: 0001784
phosphotyrosine binding
GO: 0004725
protein tyrosine phosphatase activity
GO: 0005789
endoplasmic reticulum membrane
GO: 0006470
protein dephosphorylation
GO: 0016021
integral component of membrane
KO: K04458
protein-tyrosine phosphatase [EC:3.1.3.48]
ReactionKEGG: R02585
Protein tyrosine phosphate + H2O <=> Protein tyrosine + Orthophosphate
KO: K18018
tyrosine-protein phosphatase non-receptor type 5 [EC:3.1.3.48]
ReactionKEGG: R02585
Protein tyrosine phosphate + H2O <=> Protein tyrosine + Orthophosphate
OMIM: 176879 PROTEIN-TYROSINE PHOSPHATASE, NONRECEPTOR-TYPE, 5; PTPN5
footnotes:
- Linkage disequilibrium R2 is based on founders in HapMap r27 CEU population