TRAF3
TNF receptor associated factor 3, the group of Zinc fingers TRAF-type|TNF receptor associated factors|Ring finger proteins
Basic information
Region (hg38): 14:102777449-102911500
Links
Phenotypes
GenCC
Source:
- TRAF3 haploinsufficiency (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Encephalopathy, acute, infection-induceed (herpes-specific), susceptibility to, 5 | AD | Allergy/Immunology/Infectious | Individuals may be susceptible to severe herpes simplex virus infections (eg, herpes encephalitis has been described), and awareness may allow early diagnosis and treatment (eg, with acyclovir, which has been reported as effective in the reported individual), potentially decreasing morbidity and mortality | Allergy/Immunology/Infectious | 20832341 |
ClinVar
This is a list of variants' phenotypes submitted to
- TRAF3-related disorder (1 variants)
- TRAF3 haploinsufficiency (1 variants)
- Herpes simplex encephalitis, susceptibility to, 3 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAF3 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.
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 | 98 | 10 | 109 | |||
| missense | 140 | 142 | ||||
| nonsense | 6 | |||||
| start loss | 0 | |||||
| frameshift | 7 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 152 | 99 | 11 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TRAF3 | protein_coding | protein_coding | ENST00000560371 | 10 | 134025 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00131 | 125743 | 0 | 4 | 125747 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.99 | 184 | 339 | 0.543 | 0.0000227 | 3799 |
| Missense in Polyphen | 20 | 113.85 | 0.17567 | 1273 | ||
| Synonymous | -1.06 | 154 | 138 | 1.12 | 0.0000102 | 1022 |
| Loss of Function | 4.56 | 2 | 28.1 | 0.0711 | 0.00000152 | 325 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000354 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Regulates pathways leading to the activation of NF- kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa- B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:20185819}.;
- Disease
- DISEASE: Encephalopathy, acute, infection-induced, Herpes- specific, 5 (IIAE5) [MIM:614849]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:20832341}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis C - 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);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Apoptosis Modulation and Signaling;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;IL17 signaling pathway;Apoptosis;Apoptotic Signaling Pathway;TLR4 Signaling and Tolerance;Toll-like Receptor Signaling;RIG-I-like Receptor Signaling;Oxidative Damage;Toll-like Receptor Signaling Pathway;TWEAK;tnfr2 signaling pathway;cd40l signaling pathway;yaci and bcma stimulation of b cell immune responses;TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;TICAM1-dependent activation of IRF3/IRF7;Toll Like Receptor 3 (TLR3) Cascade;Toll-Like Receptors Cascades;Post-translational protein modification;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Metabolism of proteins;Innate Immune System;Immune System;TRAF3-dependent IRF activation pathway;Negative regulators of DDX58/IFIH1 signaling;Ovarian tumor domain proteases;Deubiquitination;TNFalpha;Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;RANKL;CD40/CD40L signaling
(Consensus)
Recessive Scores
- pRec
- 0.298
Intolerance Scores
- loftool
- rvis_EVS
- -0.45
- rvis_percentile_EVS
- 24.33
Haploinsufficiency Scores
- pHI
- 0.144
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.569
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Traf3
- 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); hematopoietic system phenotype; liver/biliary system phenotype; renal/urinary system phenotype; immune system phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- regulation of cytokine production;toll-like receptor signaling pathway;apoptotic process;signal transduction;Toll signaling pathway;protein ubiquitination;protein deubiquitination;regulation of proteolysis;negative regulation of NF-kappaB transcription factor activity;regulation of interferon-beta production;tumor necrosis factor-mediated signaling pathway;TRIF-dependent toll-like receptor signaling pathway;regulation of apoptotic process;innate immune response;regulation of defense response to virus
- Cellular component
- mitochondrion;endosome;cytosol;cytoplasmic side of plasma membrane;protein-containing complex;CD40 receptor complex
- Molecular function
- ubiquitin-protein transferase activity;tumor necrosis factor receptor binding;protein binding;zinc ion binding;protein kinase binding;protein phosphatase binding;ubiquitin protein ligase binding;thioesterase binding