AP1S3

Chr 2AD

adaptor related protein complex 1 subunit sigma 3

Also known as: PSORS15, sigma1C

NCBI Gene: 130340 ENSG00000152056 UniProt: Q96PC3 OMIM: 615781

The AP1S3 protein is a subunit of clathrin-associated adaptor protein complex 1 that mediates protein sorting in the late-Golgi/trans-Golgi network and endosomes, including trafficking of TLR3. Mutations cause autosomal dominant pustular psoriasis (psoriasis 15), which primarily affects the skin rather than the nervous system. This gene shows low constraint to loss-of-function variants (pLI 0.016, LOEUF 1.079), suggesting it may not be associated with severe developmental disorders.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the adaptor-related protein complex 1, sigma subunit genes. The encoded protein is a component of adaptor protein complex 1 (AP-1), one of the AP complexes involved in claathrin-mediated vesicular transport from the Golgi or endosomes. Disruption of the pathway for display of HIV-1 antigens, which prevents recognition of the virus by cytotoxic T cells, has been shown to involve the AP-1 complex (PMID: 15569716). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Psoriasis 15, pustular, susceptibility to}MIM #616106

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.016

Z-score 1.43

OE 0.47 (0.23–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.51Z-score

OE missense 0.84 (0.69–1.03)

70 obs / 83.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.23–1.08)

0≤0.351.4

Missense OE?0.84 (0.69–1.03)

0≤0.61.4

Synonymous OE?0.68

0≤1.21.6

LoF obs/exp: 4 / 8.5Missense obs/exp: 70 / 83.0Syn Z: 1.31

Background carrier burden — how many people carry a rare variant somewhere in AP1S3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

277 rare PASS variants

Rare truncating (LoF)

1 in 1,900

61 rare PASS variants

Rare synonymous (reference)

1 in 200

92 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AP1S3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 380	1 in 2,100
South Asian	~43k	1 in 190	1 in 2,500
Remaining (unassigned)	~30k	1 in 120	1 in 2,000
European (Finnish)	~27k	1 in 920	≈ 1 in 8,400
Admixed American	~22k	1 in 150	1 in 1,600
African / African American	~21k	1 in 110	1 in 1,000
East Asian	~20k	1 in 170	1 in 2,100
Ashkenazi Jewish	~13k	1 in 570	1 in 2,100
Middle Eastern	~2,884	1 in 190	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓