AP3S2

Chr 15

adaptor related protein complex 3 subunit sigma 2

Also known as: AP3S3, sigma3b

NCBI Gene: 10239 ENSG00000157823 UniProt: P59780

The AP3S2 protein is a component of the AP-3 adaptor complex that facilitates vesicle budding from the Golgi membrane and trafficking to lysosomes, and works with the BLOC-1 complex to target cargo into vesicles for delivery to neurites and nerve terminals. Mutations cause X-linked intellectual disability with features that may include neurological impairment affecting intracellular transport pathways. The gene shows low constraint against loss-of-function variants, suggesting some tolerance to disruption.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in anterograde synaptic vesicle transport and vesicle-mediated transport. Part of AP-3 adaptor complex. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.60

OE 0.79 (0.47–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.83–1.15)

106 obs / 108.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.47–1.43)

0≤0.351.4

Missense OE?0.98 (0.83–1.15)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 8 / 10.1Missense obs/exp: 106 / 108.7Syn Z: -0.89

Background carrier burden — how many people carry a rare variant somewhere in AP3S2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

331 rare PASS variants

Rare truncating (LoF)

1 in 1,900

60 rare PASS variants

Rare synonymous (reference)

1 in 170

132 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AP3S2. 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 340	1 in 2,100
South Asian	~43k	1 in 180	1 in 3,500
Remaining (unassigned)	~30k	1 in 310	1 in 650
European (Finnish)	~27k	1 in 1,000	1 in 3,700
Admixed American	~22k	1 in 320	1 in 750
African / African American	~21k	1 in 200	1 in 1,600
East Asian	~20k	1 in 160	≈ 1 in 4,800
Ashkenazi Jewish	~13k	1 in 550	≈ 1 in 5,900
Middle Eastern	~2,884	1 in 96	≈ 1 in 2,800

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓