AP1S2

Chr XXLR

adaptor related protein complex 1 subunit sigma 2

Also known as: DC22, MRX59, MRXS21, MRXS5, MRXSF, PGS, SIGMA1B

The protein serves as the small subunit of adaptor protein complex 1, which mediates clathrin recruitment to membranes and recognizes sorting signals in transmembrane cargo molecules at the Golgi complex and endosomes. Mutations cause Pettigrew syndrome, an X-linked recessive disorder. The gene is highly constrained against loss-of-function variants (pLI 0.87, LOEUF 0.45).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.451 OMIM phenotype
Clinical SummaryAP1S2
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Gene-Disease Validity (ClinGen)
X-linked syndromic complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.867
Z-score 2.38
OE 0.00 (0.000.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.01Z-score
OE missense 0.26 (0.170.40)
15 obs / 58.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.45)
00.351.4
Missense OE0.26 (0.170.40)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 0 / 6.6Missense obs/exp: 15 / 58.2Syn Z: -0.42

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AP1S2 · 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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