CAP1

Chr 1

cyclase associated actin cytoskeleton regulatory protein 1

Also known as: CAP, CAP1-PEN

NCBI Gene: 10487ENSG00000131236UniProt: Q01518OMIM: 617801

The protein directly regulates actin filament dynamics and is involved in developmental and morphological processes including mRNA localization and cell polarity establishment. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and movement abnormalities. The gene shows moderate constraint against loss-of-function variants, indicating some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.55
Clinical Summary— CAP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 71 VUS of 102 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.020
Z-score 3.32
OE 0.30 (0.18–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.27Z-score
OE missense 0.78 (0.69–0.88)
205 obs / 263.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.18–0.55)
0≤0.351.4
Missense OE0.78 (0.69–0.88)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 8 / 26.4Missense obs/exp: 205 / 263.2Syn Z: 0.53
DN
0.6938th %ile
GOF
0.5268th %ile
LOF
0.2582th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS71
Likely Benign1
Benign2
6
Pathogenic
2
Likely Pathogenic
71
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
68
3
0
71
Likely Benign
0
1
0
0
1
Benign
0
0
0
2
2
Total06911282

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

View in ClinVar →

Protein Context — Lollipop Plot

CAP1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The RCAR12-CAP1-OST1 module controls ABA-mediated stomatal closure in Arabidopsis.
Li X et al.·PLoS Genet
2026
CAP1 deficiency protects podocytes in diabetic kidney disease by reducing mitochondria-associated endoplasmic reticulum membrane formation and mitochondrial fission.
Yao S et al.·Free Radic Biol Med
2026
Exploratory evaluation of CAP1 and ROCK2 as candidate blood biomarkers for vascular cognitive impairment.
Ren X et al.·J Alzheimers Dis
2026
Recurrent mutations in the stress regulator Cap1 reveal a trade-off between azole resistance and oxidative stress response in Candida albicans.
Zhou X et al.·PLoS Biol
2026Open Access
Vacuole and mitochondria patch (vCLAMP) protein Mcp1 reduces the pathogenesis of Candida albicans by impeding the function of Cap1-mediated oxidative stress response.
Wei Y et al.·BMC Microbiol
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients