AP1B1

Chr 22

adaptor related protein complex 1 subunit beta 1

Also known as: ADTB1, AP105A, BAM22, CLAPB2, KIDAR

NCBI Gene: 162 ENSG00000100280 UniProt: Q10567

The AP1B1 protein is a subunit of clathrin-associated adaptor protein complex 1 that mediates protein sorting in the late-Golgi/trans-Golgi network and endosomes by recruiting clathrin to membranes and recognizing sorting signals in transmembrane cargo molecules. Mutations cause keratitis-ichthyosis-deafness syndrome, which follows autosomal recessive inheritance and affects the skin, eyes, and hearing. This gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.263).

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as one of the large subunits of this complex and is a member of the adaptin protein family. This gene is a candidate meningioma gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtKeratitis-ichthyosis-deafness syndrome, autosomal recessive

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ichthyosiform erythroderma, corneal involvement, and hearing loss · AR · ClinGen 2024

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.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.26

LOEUF· LoF intol.

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Mechanism

📖

GeneReview available — AP1B1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.26LOEUF

pLI 0.998

Z-score 5.39

OE 0.13 (0.07–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.12Z-score

OE missense 0.64 (0.59–0.69)

376 obs / 588.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.26)

0≤0.351.4

Missense OE?0.64 (0.59–0.69)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 6 / 45.0Missense obs/exp: 376 / 588.9Syn Z: -0.60

Background carrier burden — how many people carry a rare variant somewhere in AP1B1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 62

1,049 rare PASS variants

Rare truncating (LoF)

1 in 1,900

100 rare PASS variants

Rare synonymous (reference)

1 in 71

559 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AP1B1. 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 82	1 in 2,600
South Asian	~43k	1 in 74	1 in 1,400
Remaining (unassigned)	~30k	1 in 52	1 in 3,600
European (Finnish)	~27k	1 in 180	1 in 2,200
Admixed American	~22k	1 in 74	≈ 1 in 5,400
African / African American	~21k	1 in 69	1 in 1,100
East Asian	~20k	1 in 63	1 in 1,100
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 71	≈ 1 in 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): 20 of 22 coding exons well covered in gnomAD exomes; exons 2, 3 marginal. Genomes: 20 of 22 (exons 2, 15 below).? see exons ↓