CASP2

Chr 7AR

caspase 2

Also known as: CASP-2, ICH1, MRT80, NEDD-2, NEDD2, PPP1R57

The protein is a cysteine-aspartic acid protease (caspase) that regulates apoptosis by forming the PIDDosome complex with PIDD1 and CRADD, which triggers cell death in response to DNA damage and other cellular stress. Biallelic mutations cause autosomal recessive intellectual developmental disorder with variant lissencephaly, affecting brain development and cognitive function. The gene is highly constrained against loss-of-function variants (LOEUF 0.658), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.661 OMIM phenotype
Clinical SummaryCASP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.66LOEUF
pLI 0.002
Z-score 2.82
OE 0.38 (0.230.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.50Z-score
OE missense 0.91 (0.821.02)
233 obs / 255.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.230.66)
00.351.4
Missense OE0.91 (0.821.02)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 9 / 23.9Missense obs/exp: 233 / 255.3Syn Z: -0.55
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateCASP2-related developmental disorder with lissencephalyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6841th %ile
GOF
0.73top 25%
LOF
0.2581th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CASP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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