AP3B1

Chr 5AR

adaptor related protein complex 3 subunit beta 1

Also known as: ADTB3, ADTB3A, HPS, HPS2, PE

NCBI Gene: 8546 ENSG00000132842 UniProt: O00203 OMIM: 603401

The AP3B1 protein is a subunit of the adaptor protein complex 3 (AP-3) that sorts transmembrane proteins to lysosomes and lysosome-related organelles including melanosomes and platelet dense granules. Mutations cause Hermansky-Pudlak syndrome type 2, an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis due to platelet storage pool deficiency, and variable pulmonary fibrosis. The gene shows significant constraint against loss-of-function variants (LOEUF 0.344), reflecting its essential cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.341 OMIM phenotype

Clinical Summary— AP3B1

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Gene-Disease Validity (ClinGen)

Hermansky-Pudlak syndrome 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.

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ClinVar Variants

78 unique Pathogenic / Likely Pathogenic· 453 VUS of 999 total submissions

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GeneReview available — AP3B1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.615

Z-score 5.63

OE 0.22 (0.14–0.34)

Highly constrained

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

Missense Constraint?

0.89Z-score

OE missense 0.89 (0.83–0.96)

508 obs / 567.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.14–0.34)

0≤0.351.4

Missense OE?0.89 (0.83–0.96)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 13 / 60.1Missense obs/exp: 508 / 567.7Syn Z: 1.37

ClinVar Variant Classifications

999 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45

Likely Pathogenic33

VUS453

Likely Benign365

Benign52

Conflicting32

Pathogenic

Likely Pathogenic

453

VUS

365

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	37	2	6	0	45
Likely Pathogenic	32	1	0	0	33
VUS	5	406	36	6	453
Likely Benign	0	8	176	181	365
Benign	0	3	47	2	52
Conflicting	—				32
Total	74	420	265	189	980

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap AP3B1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →