TRAF4
protein-codingTNF receptor associated factor 4, the group of TNF receptor associated factors|Ring finger proteins|Zinc fingers TRAF-type
Gene summary
This gene encodes a member of the TNF receptor associated factor (TRAF) family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. The encoded protein has been shown to interact with neurotrophin receptor, p75 (NTR/NTSR1), and negatively regulate NTR induced cell death and NF-kappa B activation. This protein has been found to bind to p47phox, a cytosolic regulatory factor included in a multi-protein complex known as NAD(P)H oxidase. This protein thus, is thought to be involved in the oxidative activation of MAPK8/JNK. Alternatively spliced transcript variants have been observed but the full-length nature of only one 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 ~6.9 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 TRAF4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004295.4. 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 | 1 | 1 | ||||
| missense | 56 | 1 | 57 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 60 | 0 | 1 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004286.2 | 7 | MANE Select | |
| Ensembl | ENSP00000262395.5 | 7 | MANE Select | |
| Ensembl | ENSP00000262396.6 | 5 | Standard | |
| Ensembl | ENSP00000262396.6 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Small cell lung cancer - Homo sapiens (human)
- IL-17 signaling pathway - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- ApoE and miR-146 in inflammation and atherosclerosis
- Validated transcriptional targets of TAp63 isoforms
Biological Process
- apoptotic process
- signal transduction
- activation of NF-kappaB-inducing kinase activity
- respiratory gaseous exchange
- respiratory tube development
Molecular Function
- DNA binding
- tumor necrosis factor receptor binding
- protein binding
- zinc ion binding
- protein kinase binding
Cellular Component
- nucleus
- cytoplasm
- cytoskeleton
- plasma membrane
- bicellular tight junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262395
- Coding exons
- 7
- Length
- 6973
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125727
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.42 | 178 | 295 | 0.603 | 0.0000183 | 3074 |
| Missense (PolyPhen) | 56 | 109.83 | 0.5099 | 1167 | ||
| Synonymous | -0.235 | 113 | 110 | 1.03 | 0.00000560 | 941 |
| Loss of Function | 3.75 | 3 | 22.0 | 0.137 | 0.00000117 | 231 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| 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: Adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. Plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions. {ECO:0000250, ECO:0000269|PubMed:12023963, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:16052631, ECO:0000269|PubMed:16157600, ECO:0000269|PubMed:18953416, ECO:0000269|PubMed:19937093}.;
Recessive Scores
- pRec
- 0.202
Intolerance Scores
- LoFtool
- 0.429
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.873
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |