AIFM3

Chr 22

AIF family member 3

Also known as: AIFL

NCBI Gene: 150209 ENSG00000183773 UniProt: Q96NN9 OMIM: 617298

The protein functions as an oxidoreductase that induces apoptosis through a caspase-dependent pathway and reduces mitochondrial membrane potential. Mutations in AIFM3 cause autosomal recessive severe combined immunodeficiency, typically presenting in infancy with recurrent severe infections due to profound T-cell lymphopenia. The disease primarily affects the immune system, leading to life-threatening opportunistic infections if untreated.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable oxidoreductase activity, acting on NAD(P)H. Involved in execution phase of apoptosis. Located in endoplasmic reticulum and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.99

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.61

OE 0.72 (0.53–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.00Z-score

OE missense 0.86 (0.78–0.94)

329 obs / 384.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.53–0.99)

0≤0.351.4

Missense OE?0.86 (0.78–0.94)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 27 / 37.7Missense obs/exp: 329 / 384.0Syn Z: 0.12

Background carrier burden — how many people carry a rare variant somewhere in AIFM3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

804 rare PASS variants

Rare truncating (LoF)

1 in 630

145 rare PASS variants

Rare synonymous (reference)

1 in 110

350 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AIFM3. 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 78	1 in 620
South Asian	~43k	1 in 53	1 in 1,300
Remaining (unassigned)	~30k	1 in 50	1 in 1,200
European (Finnish)	~27k	1 in 100	1 in 280
Admixed American	~22k	1 in 73	1 in 970
African / African American	~21k	1 in 52	1 in 700
East Asian	~20k	1 in 81	1 in 1,200
Ashkenazi Jewish	~13k	1 in 290	1 in 930
Middle Eastern	~2,884	1 in 86	≈ 1 in 1,400

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 ↓