TRAF4

Chr 17

TNF receptor associated factor 4

Also known as: CART1, MLN62, RNF83

NCBI Gene: 9618 ENSG00000076604 UniProt: Q9BUZ4

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.936

Z-score 3.75

OE 0.14 (0.06–0.35)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.42Z-score

OE missense 0.60 (0.53–0.68)

178 obs / 295.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.06–0.35)

0≤0.351.4

Missense OE?0.60 (0.53–0.68)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 3 / 22.0Missense obs/exp: 178 / 295.1Syn Z: -0.23

Background carrier burden — how many people carry a rare variant somewhere in TRAF4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

554 rare PASS variants

Rare truncating (LoF)

1 in 450

57 rare PASS variants

Rare synonymous (reference)

1 in 260

272 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TRAF4; this gene does not show strong loss-of-function constraint by this measure. 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 150	1 in 1,200
South Asian	~43k	1 in 110	1 in 760
Remaining (unassigned)	~30k	1 in 110	1 in 330
European (Finnish)	~27k	1 in 290	none seen
Admixed American	~22k	1 in 110	1 in 390
African / African American	~21k	1 in 160	1 in 810
East Asian	~20k	1 in 170	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 980	1 in 1,600
Middle Eastern	~2,884	1 in 130	1 in 470

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓