BIRC7

Chr 20

baculoviral IAP repeat containing 7

Also known as: KIAP, LIVIN, ML-IAP, MLIAP, RNF50

NCBI Gene: 79444 ENSG00000101197 UniProt: Q96CA5 OMIM: 605737

The protein encoded by this gene is an inhibitor of apoptosis protein that regulates cell death by inhibiting caspases 3, 7, and 9, and functions as an E3 ubiquitin ligase to promote cell survival. This gene is not highly constrained against loss-of-function variants and is not currently associated with established Mendelian pediatric neurological disorders. Mutations in BIRC7 have been linked to cancer progression rather than developmental neurological conditions.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the inhibitor of apoptosis protein (IAP) family, and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is essential for inhibitory activity and interacts with caspases, while the RING finger domain sometimes enhances antiapoptotic activity but does not inhibit apoptosis alone. Elevated levels of the encoded protein may be associated with cancer progression and play a role in chemotherapy sensitivity. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jul 2013]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.34

Clinical Summary— BIRC7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 VUS of 52 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.000

Z-score 0.60

OE 0.83 (0.53–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.89–1.13)

191 obs / 190.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.53–1.34)

0≤0.351.4

Missense OE?1.00 (0.89–1.13)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 12 / 14.5Missense obs/exp: 191 / 190.6Syn Z: -1.01

This gene — mechanism propensity

0.6065th %ile

GOF

0.6639th %ile

LOF

0.3550th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Likely Benign8

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	39	39
Likely Benign	8	8
Benign	2	2
Total	49	49

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

47 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap BIRC7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →