TRAF7

Chr 16AD

TNF receptor associated factor 7

Also known as: CAFDADD, RFWD1, RNF119

NCBI Gene: 84231 ENSG00000131653 UniProt: Q6Q0C0 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiac, facial, and digital anomalies with developmental delayMIM #618164

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · syndromic complex neurodevelopmental disorder · AD · ClinGen 2023

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Multiple*

Mechanism· predicted

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 OE?0.28 (0.17–0.46)

0≤0.351.4

Missense OE?0.56 (0.51–0.63)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 11 / 39.9Missense obs/exp: 248 / 440.6Syn Z: -1.53

Background carrier burden — how many people carry a rare variant somewhere in TRAF7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 89

756 rare PASS variants

Rare truncating (LoF)

1 in 3,100

107 rare PASS variants

Rare synonymous (reference)

1 in 66

426 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRAF7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 3,300
South Asian	~43k	1 in 90	1 in 2,400
Remaining (unassigned)	~30k	1 in 86	1 in 3,800
European (Finnish)	~27k	1 in 280	1 in 4,900
Admixed American	~22k	1 in 99	≈ 1 in 5,300
African / African American	~21k	1 in 110	1 in 1,300
East Asian	~20k	1 in 74	1 in 2,200
Ashkenazi Jewish	~13k	1 in 560	1 in 1,600
Middle Eastern	~2,884	1 in 110	1 in 400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 20 coding exons well covered in gnomAD exomes and genomes.? see exons ↓