TRAF5
protein-codingTNF receptor associated factor 5, the group of Zinc fingers TRAF-type|TNF receptor associated factors|Ring finger proteins
Gene summary
The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and contains a meprin and TRAF homology (MATH) domain, a RING-type zinc finger, and two TRAF-type zinc fingers. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein is one of the components of a multiple protein complex which binds to tumor necrosis factor (TNF) receptor cytoplasmic domains and mediates TNF-induced activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.3 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 TRAF5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001033910.3. 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 | 1 | 1 | ||||
| missense | 82 | 1 | 83 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 1 | 85 | 2 | 0 | 88 |
Highest pathogenic variant AF is 0.0000037173525
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001029082.1 | 10 | MANE Select | |
| Ensembl | ENSP00000261464.5 | 10 | MANE Select | |
| RefSeq | NP_001306136.1 | 10 | Standard | |
| RefSeq | NP_004610.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Small cell lung cancer - Homo sapiens (human)
- TNF signaling pathway - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- NOD-like receptor signaling pathway - Homo sapiens (human)
- IL-17 signaling pathway - Homo sapiens (human)
Biological Process
- apoptotic process
- signal transduction
- regulation of apoptotic process
- positive regulation of I-kappaB kinase/NF-kappaB signaling
- positive regulation of DNA-binding transcription factor activity
Molecular Function
- tumor necrosis factor receptor binding
- protein binding
- zinc ion binding
- ubiquitin protein ligase binding
- thioesterase binding
Cellular Component
- centrosome
- cytosol
- cytoplasmic side of plasma membrane
- protein-containing complex
- CD40 receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261464
- Coding exons
- 10
- Length
- 48332
- Individuals with no LoFs
- 125661
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 86
- Defined
- 125748
- p
- 0.000346
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.960 | 252 | 299 | 0.844 | 0.0000159 | 3707 |
| Missense (PolyPhen) | 82 | 111.92 | 0.73269 | 1298 | ||
| Synonymous | 1.07 | 96 | 110 | 0.871 | 0.00000534 | 987 |
| Loss of Function | 1.18 | 22 | 28.9 | 0.762 | 0.00000146 | 359 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00039 | 0.00037 | rare |
| Latino/Admixed American | 0.00037 | 0.00035 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00043 | 0.00044 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00033 | 0.00031 | rare |
| South Asian | 0.00083 | 0.00078 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. {ECO:0000269|PubMed:15121867}.;
Recessive Scores
- pRec
- 0.161
Intolerance Scores
- LoFtool
- 0.957
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.34
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.227
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |