BIRC3

Chr 11

baculoviral IAP repeat containing 3

Also known as: AIP1, API2, CIAP2, HAIP1, HIAP1, IAP-1, MALT2, MIHC

NCBI Gene: 330 ENSG00000023445 UniProt: Q13489 OMIM: 601721

This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]

OMIM Research

OMIM 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

102

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.066

Z-score 3.37

OE 0.28 (0.16–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.15Z-score

OE missense 0.82 (0.74–0.91)

254 obs / 311.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.16–0.52)

0≤0.351.4

Missense OE?0.82 (0.74–0.91)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 7 / 25.3Missense obs/exp: 254 / 311.1Syn Z: 0.46

Background carrier burden — how many people carry a rare variant somewhere in BIRC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

722 rare PASS variants

Rare truncating (LoF)

1 in 5,000

56 rare PASS variants

Rare synonymous (reference)

1 in 150

272 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BIRC3. 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 160	1 in 4,900
South Asian	~43k	1 in 66	1 in 7,100
Remaining (unassigned)	~30k	1 in 100	≈ 1 in 7,100
European (Finnish)	~27k	1 in 540	≈ 1 in 20,000
Admixed American	~22k	1 in 86	≈ 1 in 5,200
African / African American	~21k	1 in 93	≈ 1 in 5,600
East Asian	~20k	1 in 120	1 in 1,500
Ashkenazi Jewish	~13k	1 in 840	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 99	≈ 1 in 2,800

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): 7 of 8 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 8.? see exons ↓