CASP2

Chr 7AR

caspase 2

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

NCBI Gene: 835ENSG00000106144UniProt: P42575

This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Caspases mediate cellular apoptosis through the proteolytic cleavage of specific protein substrates. The encoded protein may function in stress-induced cell death pathways, cell cycle maintenance, and the suppression of tumorigenesis. Increased expression of this gene may play a role in neurodegenerative disorders including Alzheimer's disease, Huntington's disease and temporal lobe epilepsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 80, with variant lissencephalyMIM #620653
AR
118
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CASP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 51 VUS of 118 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.66LOEUF
pLI 0.002
Z-score 2.82
OE 0.38 (0.23–0.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.50Z-score
OE missense 0.91 (0.82–1.02)
233 obs / 255.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.23–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.82–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 9 / 23.9Missense obs/exp: 233 / 255.3Syn Z: -0.55

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic2
VUS51
Likely Benign12
Benign2
Conflicting1
50
Pathogenic
2
Likely Pathogenic
51
VUS
12
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
48
0
50
Likely Pathogenic
1
0
1
0
2
VUS
0
45
6
0
51
Likely Benign
0
2
1
9
12
Benign
0
0
0
2
2
Conflicting
—1
Total3475611118

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

View 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.

Gene2Phenotype Curations

CASP2-related developmental disorder with lissencephaly

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
splice donor variantframeshift variantstop gained

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly

MIM #620653

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An unexpected role for caspase-2 in neuroblastoma.
Dorstyn L et al.·Cell Death Dis
2014
Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly.
Uctepe E et al.·Eur J Hum Genet
2024
Regulatory Role of miRNAs and lncRNAs in Gout.
Shu J et al.·Comput Math Methods Med
2022
Lung cancer cells and their sensitivity/resistance to cisplatin chemotherapy: Role of microRNAs and upstream mediators.
Ashrafizadeh M et al.·Cell Signal
2021Review
Diagnostic and Predictive Value of LncRNA MCM3AP-AS1 in Sepsis and Its Regulatory Role in Sepsis-Induced Myocardial Dysfunction.
Wei Y et al.·Cardiovasc Toxicol
2024
Divergent modulation of neuronal differentiation by caspase-2 and -9.
Pistritto G et al.·PLoS One
2012
Inhibition of microRNA-383 has tumor suppressive effect in human epithelial ovarian cancer through the action on caspase-2 gene.
Liu J et al.·Biomed Pharmacother
2016
The association of taxane resistance genes with the clinical course of ovarian carcinoma.
Ehrlichova M et al.·Genomics
2013
Caspase-2 deficiency promotes aberrant DNA-damage response and genetic instability.
Dorstyn L et al.·Cell Death Differ
2012
Prognostic biomarkers of IFNb therapy in multiple sclerosis patients.
Baranzini SE et al.·Mult Scler
2015Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cerebral Palsy

The Impact of Commercial Blenderized Formula on Caloric Needs, Gastrointestinal Symptoms, and Gut Microbiome in Children With Cerebral Palsy (CP)

NOT YET RECRUITING
NCT06488560Phase NAThe University of Texas Health Science Center, HoustonStarted 2024-08-01
commercial blenderized tube feed (CBTF)commercial formulas (CF)

External Resources

Links to major genomics databases and tools