TRAF6
TNF receptor associated factor 6, the group of TNF receptor associated factors|Ring finger proteins|Zinc fingers TRAF-type
Basic information
Region (hg38): 11:36483768-36510272
Links
Phenotypes
GenCC
Source:
- autosomal dominant hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (11 variants)
- not provided (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAF6 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 10 | 11 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 10 | 3 | 0 |
Variants in TRAF6
This is a list of pathogenic ClinVar variants found in the TRAF6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-36490149-T-G | not specified | Uncertain significance (Apr 05, 2023) | ||
| 11-36490202-C-T | not specified | Uncertain significance (Nov 18, 2022) | ||
| 11-36490335-C-T | not specified | Uncertain significance (Dec 21, 2022) | ||
| 11-36490374-C-T | not specified | Uncertain significance (Aug 12, 2021) | ||
| 11-36490551-A-G | not specified | Uncertain significance (Aug 13, 2021) | ||
| 11-36490563-C-T | not specified | Uncertain significance (Sep 14, 2022) | ||
| 11-36490598-A-C | not specified | Uncertain significance (Dec 14, 2023) | ||
| 11-36495046-A-G | not specified | Uncertain significance (Dec 21, 2023) | ||
| 11-36497128-T-C | not specified | Likely benign (Apr 06, 2023) | ||
| 11-36497134-C-T | not specified | Uncertain significance (Feb 03, 2022) | ||
| 11-36497165-T-C | Likely benign (Mar 29, 2018) | |||
| 11-36497186-A-T | Likely benign (May 31, 2018) | |||
| 11-36497194-T-C | not specified | Uncertain significance (Dec 04, 2021) | ||
| 11-36497233-C-T | not specified | Likely benign (Nov 10, 2023) | ||
| 11-36497235-A-G | TRAF6-related disorder | Likely benign (Feb 21, 2024) | ||
| 11-36497274-T-TA | not specified | Benign (-) | ||
| 11-36498507-C-T | not specified | Uncertain significance (May 27, 2022) | ||
| 11-36498595-T-G | not specified | Uncertain significance (Feb 02, 2024) | ||
| 11-36501283-C-T | not specified | Uncertain significance (Nov 21, 2023) | ||
| 11-36501385-T-C | not specified | Uncertain significance (Aug 12, 2021) | ||
| 11-36501457-C-T | not specified | Uncertain significance (May 23, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TRAF6 | protein_coding | protein_coding | ENST00000526995 | 6 | 23246 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00261 | 125738 | 0 | 6 | 125744 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.72 | 162 | 293 | 0.553 | 0.0000165 | 3513 |
| Missense in Polyphen | 45 | 127.37 | 0.35329 | 1566 | ||
| Synonymous | 0.447 | 94 | 99.7 | 0.943 | 0.00000524 | 953 |
| Loss of Function | 4.13 | 1 | 21.9 | 0.0458 | 0.00000129 | 255 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000353 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c- Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. {ECO:0000269|PubMed:11057907, ECO:0000269|PubMed:12140561, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:17135271, ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:18347055, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:8837778}.;
- Pathway
- Pertussis - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Endocytosis - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Apoptosis Modulation and Signaling;IL-1 signaling pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;IL17 signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;EBV LMP1 signaling;Structural Pathway of Interleukin 1 (IL-1);Melatonin metabolism and effects;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NF-kB survival signaling;Interleukin-1 Induced Activation of NF-kappa-B;TGF-beta Signaling Pathway;MAPK Signaling Pathway;MAPK and NFkB Signalling Pathways Inhibited by Yersinia YopJ;TLR4 Signaling and Tolerance;Toll-like Receptor Signaling;RIG-I-like Receptor Signaling;Simplified Depiction of MYD88 Distinct Input-Output Pathway;Oxidative Damage;Fibrin Complement Receptor 3 Signaling Pathway;EMT transition in Colorectal Cancer;T-Cell antigen Receptor (TCR) Signaling Pathway;Toll-like Receptor Signaling Pathway;TLR NFkB;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Signaling by Interleukins;p75NTR signals via NF-kB;cd40l signaling pathway;yaci and bcma stimulation of b cell immune responses;TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling;signal transduction through il1r;nf-kb signaling pathway;toll-like receptor pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;TICAM1, RIP1-mediated IKK complex recruitment ;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;B cell receptor signaling;Toll-Like Receptors Cascades;Downstream TCR signaling;TCR signaling;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Post-translational protein modification;TRAF6 mediated IRF7 activation;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Metabolism of proteins;Interleukin-1 signaling;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Fc epsilon receptor (FCERI) signaling;IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation;Innate Immune System;Immune System;Adaptive Immune System;IL-1 NFkB;IL-1 p38;IL-1 JNK;IL1;TLR p38;IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;activated TAK1 mediates p38 MAPK activation;BDNF;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;NRIF signals cell death from the nucleus;MyD88 dependent cascade initiated on endosome;Ub-specific processing proteases;BCR signaling pathway;bone remodeling;PIP3 activates AKT signaling;Ovarian tumor domain proteases;Deubiquitination;p75NTR recruits signalling complexes;NF-kB is activated and signals survival;Death Receptor Signalling;Regulated proteolysis of p75NTR;p75 NTR receptor-mediated signalling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;FCERI mediated NF-kB activation;TLR ECSIT MEKK1 JNK;TLR ECSIT MEKK1 p38;TNFalpha;TLR JNK;IKK complex recruitment mediated by RIP1;TRAF6-mediated induction of TAK1 complex within TLR4 complex;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Canonical NF-kappaB pathway;Intracellular signaling by second messengers;IRAK2 mediated activation of TAK1 complex;IRAK1 recruits IKK complex;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;RANKL;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;CD40/CD40L signaling;TCR signaling in naïve CD8+ T cells;Regulation of p38-alpha and p38-beta;p75(NTR)-mediated signaling;Cell death signalling via NRAGE, NRIF and NADE;p38 MAPK signaling pathway;IL1-mediated signaling events;TCR signaling in naïve CD4+ T cells;Interleukin-1 family signaling;CD4 T cell receptor signaling-NFkB cascade;TICAM1,TRAF6-dependent induction of TAK1 complex;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.595
Intolerance Scores
- loftool
- 0.0444
- rvis_EVS
- -0.54
- rvis_percentile_EVS
- 20.26
Haploinsufficiency Scores
- pHI
- 0.335
- hipred
- Y
- hipred_score
- 0.628
- ghis
- 0.555
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Traf6
- Phenotype
- immune system phenotype; renal/urinary system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; embryo phenotype; liver/biliary system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;activation of MAPK activity;protein polyubiquitination;ossification;neural tube closure;stimulatory C-type lectin receptor signaling pathway;toll-like receptor signaling pathway;positive regulation of T cell cytokine production;MyD88-dependent toll-like receptor signaling pathway;cellular response to DNA damage stimulus;I-kappaB kinase/NF-kappaB signaling;activation of NF-kappaB-inducing kinase activity;JNK cascade;protein deubiquitination;antigen processing and presentation of exogenous peptide antigen via MHC class II;osteoclast differentiation;membrane protein intracellular domain proteolysis;positive regulation of protein ubiquitination;positive regulation of lipopolysaccharide-mediated signaling pathway;activation of protein kinase activity;positive regulation of interleukin-2 production;toll-like receptor 9 signaling pathway;Fc-epsilon receptor signaling pathway;T-helper 1 type immune response;positive regulation of T cell proliferation;odontogenesis of dentin-containing tooth;myeloid dendritic cell differentiation;positive regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of JUN kinase activity;positive regulation of interleukin-12 biosynthetic process;positive regulation of interleukin-6 biosynthetic process;bone resorption;positive regulation of osteoclast differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell development;positive regulation of smooth muscle cell proliferation;T cell receptor signaling pathway;regulation of immunoglobulin secretion;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;protein autoubiquitination;nucleotide-binding oligomerization domain containing signaling pathway;interleukin-1-mediated signaling pathway;protein K63-linked ubiquitination;response to interleukin-1;cellular response to lipopolysaccharide;cellular response to cytokine stimulus;positive regulation of NIK/NF-kappaB signaling;positive regulation of leukocyte adhesion to vascular endothelial cell;positive regulation of transcription regulatory region DNA binding
- Cellular component
- nucleus;cytoplasm;lipid droplet;cytosol;plasma membrane;cell cortex;cytoplasmic side of plasma membrane;endosome membrane;protein-containing complex;CD40 receptor complex;perinuclear region of cytoplasm
- Molecular function
- ubiquitin-protein transferase activity;tumor necrosis factor receptor binding;protein binding;zinc ion binding;protein kinase binding;mitogen-activated protein kinase kinase kinase binding;ubiquitin conjugating enzyme binding;ubiquitin protein ligase binding;thioesterase binding;identical protein binding;histone deacetylase binding;protein kinase B binding;protein N-terminus binding;ubiquitin protein ligase activity