CAP2

Chr 6AR

cyclase associated actin cytoskeleton regulatory protein 2

ENSG00000112186UniProt: P40123

Involved in the regulation of actin polymerization

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 2IMIM #620462
AR
96
ClinVar variants
20
Pathogenic / LP
0.70
pLI score
0
Active trials
Clinical Summary— CAP2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.70) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 72 VUS of 96 total submissions
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.41LOEUF
pLI 0.699
Z-score 3.80
OE 0.19 (0.10–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.10Z-score
OE missense 0.81 (0.73–0.91)
221 obs / 272.2 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.0.19 (0.10–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.91)
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.0.93
0≤1.21.6
LoF obs/exp: 5 / 25.9Missense obs/exp: 221 / 272.2Syn Z: 0.53

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic2
VUS72
Likely Benign3
Benign1
18
Pathogenic
2
Likely Pathogenic
72
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
16
0
18
Likely Pathogenic
0
0
2
0
2
VUS
0
67
5
0
72
Likely Benign
0
3
0
0
3
Benign
0
0
0
1
1
Total27023196

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

View in ClinVar →

Protein Context — Lollipop Plot

CAP2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cardiomyopathy, dilated, 2I

MIM #620462

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A homozygous CAP2 pathogenic variant in a neonate presenting with rapidly progressive cardiomyopathy and nemaline rods.
Gurunathan S et al.·Am J Med Genet A
2022Case report
CAP2 mutation leads to impaired actin dynamics and associates with supraventricular tachycardia and dilated cardiomyopathy.
Aspit L et al.·J Med Genet
2019
p53 maintains lineage fidelity during lung capillary injury-repair in neonatal hyperoxia.
Vila Ellis L et al.·JCI Insight
2025
A linkage and exome study implicates rare variants of KANK4 and CAP2 in bipolar disorder in a multiplex family.
Anjanappa RM et al.·Bipolar Disord
2020
CAP2 contributes to Parkinson's disease diagnosed by neutrophil extracellular trap-related immune activity.
Li X et al.·Front Immunol
2024
Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma.
Masugi Y et al.·Pathol Int
2015
Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries.
Holmes DR Jr et al.·J Am Coll Cardiol
2019Clinical trial
The vascular phenotype of BPD: new basic science insights-new precision medicine approaches.
Durlak W et al.·Pediatr Res
2024Review
Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure.
Dukkipati SR et al.·J Am Coll Cardiol
2022
Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer.
Xu L et al.·Oncol Rep
2016
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools