AP2S1

Chr 19

adaptor related protein complex 2 subunit sigma 1

Also known as: AP17, CLAPS2, FBH3, FBHOk, HHC3

NCBI Gene: 1175ENSG00000042753UniProt: P53680

One of two major clathrin-associated adaptor complexes, AP-2, is a heterotetramer which is associated with the plasma membrane. This complex is composed of two large chains, a medium chain, and a small chain. This gene encodes the small chain of this complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHypocalciuric hypercalcemia, familial 3

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
18
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.50
LOEUF
GOF
Mechanism· predicted
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GeneReview available — AP2S1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.50LOEUF
pLI 0.785
Z-score 2.55
OE 0.11 (0.04–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.86Z-score
OE missense 0.16 (0.11–0.25)
15 obs / 92.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.11 (0.04–0.50)
0≤0.351.4
Missense OE?0.16 (0.11–0.25)
0≤0.61.4
Synonymous OE?0.99
0≤1.21.6
LoF obs/exp: 1 / 9.4Missense obs/exp: 15 / 92.4Syn Z: 0.06

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

AP2S1 · protein map & ClinVar variants

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

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