TRAF7

Chr 16AD

TNF receptor associated factor 7

Also known as: CAFDADD, RFWD1, RNF119

NCBI Gene: 84231ENSG00000131653UniProt: Q6Q0C0OMIM: 606692

TRAF7 encodes an E3 ubiquitin and SUMO-protein ligase that regulates innate immunity, inflammation, and apoptosis through protein modification and degradation pathways. Autosomal dominant mutations cause cardiac, facial, and digital anomalies with developmental delay, representing a recognizable multiple congenital anomaly syndrome. This condition affects multiple organ systems with congenital malformations apparent from birth.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.461 OMIM phenotype
Clinical Summary— TRAF7
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 48 VUS of 105 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.46LOEUF
pLI 0.022
Z-score 4.24
OE 0.28 (0.17–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.26Z-score
OE missense 0.56 (0.51–0.63)
248 obs / 440.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.28 (0.17–0.46)
0≤0.351.4
Missense OE0.56 (0.51–0.63)
0≤0.61.4
Synonymous OE1.14
0≤1.21.6
LoF obs/exp: 11 / 39.9Missense obs/exp: 248 / 440.6Syn Z: -1.53
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTRAF7-related developmental delay congenital anomalies and dysmorphic featuresOTHERAD
DN
0.6840th %ile
GOF
0.6443th %ile
LOF
0.4136th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFThe second group included eight (31%) BAP1-wild-type tumors: two with TP53 mutations, one with a TRAF7 activating mutation, one with a SUZ12 inactivating mutation, and three with ALK rearrangements that we previously published.PMID:32504035

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic4
VUS48
Likely Benign37
Benign6
Conflicting1
9
Pathogenic
4
Likely Pathogenic
48
VUS
37
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
3
1
0
4
VUS
4
41
3
0
48
Likely Benign
0
9
4
24
37
Benign
0
0
3
3
6
Conflicting
—1
Total4532027105

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRAF7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
TRAF7-Mutated Fibromyxoid Spindle Cell Tumor of Bone: An Osseous Case Expanding the Spectrum of TRAF7-Mutated Tumors With Over 20 Years Clinical Follow-Up.
Warmke LM et al.·Genes Chromosomes Cancer
2026Open AccessNatural history
The PERISCOPE Cohort: A Retrospective Study of Clinicopathological and TRAF7 Genetic Findings in Intraneural Perineurioma.
Cavalcanti EBU et al.·Eur J Neurol
2026Open AccessCohort
Primary TRAF7-Mutated Myxoid Mesenchymal Tumor With Predominant Epithelioid Morphology: Expanding the Morphologic Spectrum of TRAF7-Mutated Myxoid Mesenchymal Tumors.
Naous R et al.·Cureus
2025Open Access
TRAF7 in signaling and disease: emerging mechanisms and clinical implications.
Orock A et al.·Mol Med
2025Open AccessFunctional
TRAF7-Mutated Myxoid and Spindle Cell Mesenchymal Tumor Occurring in a Pediatric Patient in the Post-Transplant Setting: Expanding the Spectrum of TRAF7-Mutated Tumors.
Torres S et al.·Genes Chromosomes Cancer
2025
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients