TRAF2
protein-codingTNF receptor associated factor 2, the group of TNF receptor associated factors|MicroRNA protein coding host genes|Ring finger proteins|Zinc fingers TRAF-type
Gene summary
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRAF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021138.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 3 | 5 | |||
| missense | 64 | 3 | 67 | |||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 73 | 3 | 3 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066961.2 | 10 | MANE Select | |
| Ensembl | ENSP00000247668.2 | 10 | MANE Select | |
| Ensembl | ENSP00000397653.1 | 3 | Standard | |
| Ensembl | ENSP00000405860.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adipocytokine signaling pathway - Homo sapiens (human)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
- Small cell lung cancer - Homo sapiens (human)
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
Biological Process
- positive regulation of T cell cytokine production
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- signal transduction
- I-kappaB kinase/NF-kappaB signaling
- activation of NF-kappaB-inducing kinase activity
Molecular Function
- ubiquitin-protein transferase activity
- tumor necrosis factor receptor binding
- CD40 receptor binding
- protein binding
- zinc ion binding
Cellular Component
- ubiquitin ligase complex
- nucleoplasm
- cytosol
- cell cortex
- cytoplasmic side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000247668
- Coding exons
- 10
- Length
- 44696
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125745
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 252 | 332 | 0.759 | 0.0000221 | 3282 |
| Missense (PolyPhen) | 26 | 80.22 | 0.32411 | 819 | ||
| Synonymous | -2.34 | 179 | 143 | 1.25 | 0.0000110 | 975 |
| Loss of Function | 4.56 | 0 | 24.2 | 0.00 | 0.00000118 | 273 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'- linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin- protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE. {ECO:0000269|PubMed:10346818, ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:11907583, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:18981220, ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:19506082, ECO:0000269|PubMed:19810754, ECO:0000269|PubMed:19918265, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20047764, ECO:0000269|PubMed:20064526, ECO:0000269|PubMed:20385093, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23453969}.;
Recessive Scores
- pRec
- 0.187
Intolerance Scores
- LoFtool
- 0.165
- RVIS EVS
- -0.82
- RVIS percentile EVS
- 11.77
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |