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…

LOEUF 0.26

Clinical Summary— AP1B1

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Gene-Disease Validity (ClinGen)

ichthyosiform erythroderma, corneal involvement, and hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

13 unique Pathogenic / Likely Pathogenic· 103 VUS of 186 total submissions

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GeneReview available — AP1B1

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

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

ClinVar Variant Classifications

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic2

VUS103

Likely Benign19

Benign24

Pathogenic

Likely Pathogenic

103

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	2	1	0	11
Likely Pathogenic	1	1	0	0	2
VUS	2	99	1	1	103
Likely Benign	0	7	4	8	19
Benign	0	0	21	3	24
Total	11	109	27	12	159

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

32 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap AP1B1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →