AP1B1

Chr 22AR

adaptor related protein complex 1 subunit beta 1

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

NCBI Gene: 162ENSG00000100280UniProt: Q10567

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]

Primary Disease Associations & Inheritance

Keratitis-ichthyosis-deafness syndrome, autosomal recessiveMIM #242150
AR
189
ClinVar variants
44
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— AP1B1
🧬
Gene-Disease Validity (ClinGen)
ichthyosiform erythroderma, corneal involvement, and hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 102 VUS of 189 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.07–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.59–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 6 / 45.0Missense obs/exp: 376 / 588.9Syn Z: -0.60

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS102
Likely Benign19
Benign24
42
Pathogenic
2
Likely Pathogenic
102
VUS
19
Likely Benign
24
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
3
35
0
42
Likely Pathogenic
0
1
1
0
2
VUS
2
95
4
1
102
Likely Benign
0
7
4
8
19
Benign
0
0
21
3
24
Total61066512189

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

View in ClinVar →

Protein Context — Lollipop Plot

AP1B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

AP1B1-related keratitis-ichthyosis-deafness syndrome (KIDAR)

moderate
ARUndeterminedAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkin
G2P ↗
frameshift variantstop gainedmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Keratitis-ichthyosis-deafness syndrome, autosomal recessive

MIM #242150

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — AP1B1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical, biochemical and cell biological characterization of KIDAR syndrome associated with a novel AP1B1 variant.
Kaniganti T et al.·Mol Genet Metab
2025Case report
Phenotypic spectrum of autosomal recessive Keratitis-Ichthyosis-Deafness Syndrome (KIDAR) due to mutations in AP1B1.
Faghihi F et al.·Eur J Med Genet
2022Review
Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia.
Boyden LM et al.·Am J Hum Genet
2019
LAMP3 signature affects cervical cancer progression through autophagy.
Ji H et al.·BMC Cancer
2025
Novel homozygous pathogenic AP1B1 variant in autosomal recessive keratitis-ichthyosis-deafness syndrome treated with acitretin.
Caetano DG et al.·BMJ Case Rep
2025Case report
Comprehensive analysis of copper-metabolism-related genes about prognosis and immune microenvironment in osteosarcoma.
Lin Z et al.·Sci Rep
2023
Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes.
Tritto V et al.·Int J Mol Sci
2022Cohort
Lysosome-related proteins may have changes in the urinary exosomes of patients with acute gout attack.
Wang J et al.·Eur J Med Res
2025Cohort
Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome.
Alsaif HS et al.·Am J Hum Genet
2019
A patient with mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratodermia syndrome caused by AP1B1 gene variant.
Meriç R et al.·Clin Dysmorphol
2021Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools