TRAF7

Chr 16AD

TNF receptor associated factor 7

Also known as: CAFDADD, RFWD1, RNF119

NCBI Gene: 84231ENSG00000131653UniProt: Q6Q0C0

Tumor necrosis factor (TNF; see MIM 191160) receptor-associated factors, such as TRAF7, are signal transducers for members of the TNF receptor superfamily (see MIM 191190). TRAFs are composed of an N-terminal cysteine/histidine-rich region containing zinc RING and/or zinc finger motifs; a coiled-coil (leucine zipper) motif; and a homologous region that defines the TRAF family, the TRAF domain, which is involved in self-association and receptor binding.[supplied by OMIM, Apr 2004]

Primary Disease Associations & Inheritance

Cardiac, facial, and digital anomalies with developmental delayMIM #618164
AD
266
ClinVar variants
55
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— TRAF7
🧬
Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 145 VUS of 266 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.17–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.56 (0.51–0.63)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 11 / 39.9Missense obs/exp: 248 / 440.6Syn Z: -1.53

ClinVar Variant Classifications

266 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic14
VUS145
Likely Benign50
Benign10
Conflicting6
41
Pathogenic
14
Likely Pathogenic
145
VUS
50
Likely Benign
10
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
34
0
41
Likely Pathogenic
0
12
2
0
14
VUS
10
109
26
0
145
Likely Benign
0
15
7
28
50
Benign
0
1
4
5
10
Conflicting
—6
Total101447333266

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.

Gene2Phenotype Curations

TRAF7-related developmental delay congenital anomalies and dysmorphic features

strong
ADUndeterminedAltered Gene Product Structure
Dev. DisordersSkin
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cardiac, facial, and digital anomalies with developmental delay

MIM #618164

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Current treatment options for meningioma.
Apra C et al.·Expert Rev Neurother
2018Review
[Meningioma].
Sasaki H·No Shinkei Geka
2023
TRAF7 in signaling and disease: emerging mechanisms and clinical implications.
Orock A et al.·Mol Med
2025Review
European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection.
Sahm F et al.·Neuro Oncol
2025Review
Associations of meningioma molecular subgroup and tumor recurrence.
Youngblood MW et al.·Neuro Oncol
2021
Expanding the Phenotypic Spectrum of TRAF7-Related Cardiac, Facial, and Digital Anomalies With Developmental Delay: Report of 11 New Cases and Literature Review.
Palma-Milla C et al.·Pediatr Neurol
2024Review
What is new in intraneural perineurioma?
Lenartowicz KA et al.·Acta Neurochir (Wien)
2023Review
Genomic Landscape of Meningiomas.
Wang JZ et al.·Adv Exp Med Biol
2023
Clinical Characteristics and Outcomes of Patients with Well-Differentiated Papillary Peritoneal Mesothelial Tumors.
Offin M et al.·Ann Surg Oncol
2024Cohort
Novel mosaic TRAF7 likely pathogenic variant in an African American family.
Colleran JA et al.·Am J Med Genet A
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools