CAP1

Chr 1

cyclase associated actin cytoskeleton regulatory protein 1

Also known as: CAP, CAP1-PEN

NCBI Gene: 10487 ENSG00000131236 UniProt: Q01518 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2016]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.55

Clinical Summary— CAP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

68 VUS of 91 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 OE?0.30 (0.18–0.55)

0≤0.351.4

Missense OE?0.78 (0.69–0.88)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 8 / 26.4Missense obs/exp: 205 / 263.2Syn Z: 0.53

This gene — mechanism propensity

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

91 submitted variants in ClinVar

ClinVar

Classification Summary

VUS68

Likely Benign1

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	68	0	68
Likely Benign	1	0	1
Benign	0	2	2
Total	69	2	71

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap CAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →