FADD

Chr 11

Fas associated via death domain

Also known as: GIG3, IMD90, MORT1

NCBI Gene: 8772 ENSG00000168040 UniProt: Q13158

The protein encoded by this gene is an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals. Through its C-terminal death domain, this protein can be recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and thus it participates in the death signaling initiated by these receptors. Interaction of this protein with the receptors unmasks the N-terminal effector domain of this protein, which allows it to recruit caspase-8, and thereby activate the cysteine protease cascade. Knockout studies in mice also suggest the importance of this protein in early T cell development. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtInfections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · FADD-related immunodeficiency · AR · ClinGen 2026

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

171

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.28

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.28LOEUF

pLI 0.526

Z-score 1.37

OE 0.00 (0.00–1.28)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.84Z-score

OE missense 0.79 (0.67–0.93)

101 obs / 127.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.28)

0≤0.351.4

Missense OE?0.79 (0.67–0.93)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 0 / 2.2Missense obs/exp: 101 / 127.6Syn Z: -1.10

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

274 rare PASS variants

Rare truncating (LoF)

1 in 17,000

20 rare PASS variants

Rare synonymous (reference)

1 in 250

149 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FADD. 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 460	1 in 17,000
South Asian	~43k	1 in 200	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 30,000
European (Finnish)	~27k	1 in 880	≈ 1 in 16,000
Admixed American	~22k	1 in 210	≈ 1 in 22,000
African / African American	~21k	1 in 530	≈ 1 in 21,000
East Asian	~20k	1 in 570	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	1 in 580	none seen

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