CADPS

Chr 3

calcium dependent secretion activator

Also known as: CADPS1, CAPS, CAPS1, UNC-31

The protein functions as a calcium-binding protein that regulates the exocytosis of neurotransmitter-filled vesicles at synapses, acting downstream of ATP-dependent priming to mediate vesicle fusion with cell membranes. Mutations cause autosomal recessive intellectual disability, autism spectrum disorder, and seizures, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.435), indicating that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.43
Clinical SummaryCADPS
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.43LOEUF
pLI 0.000
Z-score 5.64
OE 0.31 (0.220.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.10Z-score
OE missense 0.68 (0.640.74)
525 obs / 766.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.31 (0.220.43)
00.351.4
Missense OE0.68 (0.640.74)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 24 / 77.6Missense obs/exp: 525 / 766.6Syn Z: -1.44
DN
0.6259th %ile
GOF
0.6834th %ile
LOF
0.4233th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CADPS · 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

No active trials found for this gene.

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Clinical Literature
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