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GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AP3B1
adaptor related protein complex 3 subunit beta 1
Chromosome 5 · 5q14.1
NCBI Gene: 8546Ensembl: ENSG00000132842.16HGNC: HGNC:566UniProt: A0A0S2Z5J4
170PubMed Papers
21Diseases
0Drugs
73Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmelanosome organizationGTP-dependent protein bindinglysosomal membraneHermansky-Pudlak syndrome 2Hermansky-Pudlak syndrome with neutropeniaHermansky-Pudlak syndromecancer
✦AI Summary

AP3B1 encodes the β1 subunit of the adaptor protein complex 3 (AP-3), a critical component of vesicular trafficking machinery. AP-3 functions in protein sorting within the trans-Golgi network and endosomes, mediating recognition of cargo sorting signals and recruitment of clathrin to membranes 1. AP-3B1 is essential for lysosomal biogenesis and targeting cargo to lysosomes and lysosome-related organelles, including melanosomes and platelet dense granules 1. In concert with BLOC-1, AP-3 directs neuronal cargo into vesicles for anterograde axonal transport to nerve terminals 1. Dysfunction of AP3B1 causes Hermansky-Pudlak syndrome type 2 (HPS2), an autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage pool deficiency with hemorrhagic diathesis, and severe neutropenia with recurrent infections 2. AP3B1 mutations are also associated with hemophagocytic lymphohistiocytosis (HLH) due to impaired cytotoxic granule biogenesis in CD8+ T cells and NK cells 3. Beyond genetic disease, AP3B1 demonstrates antiviral functions: it restricts rabies virus through PDIA3-mediated selective autophagy of viral glycoproteins 4 and suppresses SARS-CoV-2 replication through interactions with the viral envelope protein 5. These findings suggest AP3B1 represents a potential therapeutic target across multiple disease contexts.

Sources cited
1
AP3B1 regulates melanosome biogenesis and tyrosinase distribution in ocular tissue
PMID: 25160823
2
AP3B1 mutations cause Hermansky-Pudlak syndrome type 2 with oculocutaneous albinism, platelet dysfunction, and severe neutropenia
PMID: 36162005
3
AP3B1 is required for cytotoxic granule assembly and exocytosis in CD8+ T cells and NK cells; mutations cause hemophagocytic lymphohistiocytosis
PMID: 34868048
4
AP3B1 facilitates PDIA3-mediated selective autophagy-dependent degradation of rabies virus glycoprotein
PMID: 39128851
5
AP3B1 overexpression suppresses SARS-CoV-2 replication through interaction with viral envelope protein E
PMID: 39339853
Disease Associationsⓘ21
Hermansky-Pudlak syndrome 2Open Targets
0.83Strong
Hermansky-Pudlak syndrome with neutropeniaOpen Targets
0.68Moderate
Hermansky-Pudlak syndromeOpen Targets
0.66Moderate
cancerOpen Targets
0.55Moderate
Parkinson diseaseOpen Targets
0.47Moderate
Alzheimer diseaseOpen Targets
0.45Moderate
lysosomal storage diseaseOpen Targets
0.45Moderate
multiple sclerosisOpen Targets
0.45Moderate
neurodegenerative diseaseOpen Targets
0.45Moderate
autoinflammatory syndromeOpen Targets
0.41Moderate
Abnormality of the skeletal systemOpen Targets
0.39Weak
pulmonary fibrosisOpen Targets
0.37Weak
lung diseaseOpen Targets
0.37Weak
Hermansky-Pudlak syndrome with pulmonary fibrosisOpen Targets
0.37Weak
atrial fibrillationOpen Targets
0.35Weak
type 2 diabetes mellitusOpen Targets
0.34Weak
HIV infectionOpen Targets
0.33Weak
osteoarthritis, kneeOpen Targets
0.33Weak
obesityOpen Targets
0.31Weak
DNA methylationOpen Targets
0.27Weak
Hermansky-Pudlak syndrome 2UniProt
Pathogenic Variants73
NM_003664.5(AP3B1):c.310C>T (p.Arg104Ter)Pathogenic
Hermansky-Pudlak syndrome 2
★★☆☆2024→ Residue 104
NM_003664.5(AP3B1):c.3015_3016dup (p.Thr1006fs)Pathogenic
Hermansky-Pudlak syndrome 2
★★☆☆2024→ Residue 1006
NM_003664.5(AP3B1):c.2078-1G>ALikely pathogenic
Hermansky-Pudlak syndrome 2
★★☆☆2024
NM_003664.5(AP3B1):c.1945C>T (p.Arg649Ter)Pathogenic
Hermansky-Pudlak syndrome 2
★★☆☆2024→ Residue 649
NM_003664.5(AP3B1):c.2640del (p.Gly881fs)Pathogenic
Hermansky-Pudlak syndrome 2
★★☆☆2023→ Residue 881
NM_003664.5(AP3B1):c.177del (p.Lys59fs)Pathogenic
Hermansky-Pudlak syndrome 2|Autoinflammatory syndrome
★★☆☆2023→ Residue 59
NM_003664.5(AP3B1):c.1979G>A (p.Trp660Ter)Pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2026→ Residue 660
NM_003664.5(AP3B1):c.2675_2679del (p.Pro892fs)Pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2025→ Residue 892
NM_003664.5(AP3B1):c.1619dup (p.Ala541fs)Pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2025→ Residue 541
NM_003664.5(AP3B1):c.1789dup (p.Ile597fs)Pathogenic
Hermansky-Pudlak syndrome|Hermansky-Pudlak syndrome 2
★☆☆☆2025→ Residue 597
NM_003664.5(AP3B1):c.2072_2077+2delLikely pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2025
NM_003664.5(AP3B1):c.1344_1347dup (p.Leu450fs)Pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2025→ Residue 450
NM_003664.5(AP3B1):c.2470+1G>APathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2025
NM_003664.5(AP3B1):c.2769del (p.Lys923fs)Pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2025→ Residue 923
NM_003664.5(AP3B1):c.2249+1delPathogenic
not provided
★☆☆☆2025
NM_003664.5(AP3B1):c.1219C>T (p.Arg407Ter)Pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2025→ Residue 407
NM_003664.5(AP3B1):c.1041-2A>GLikely pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2024
NM_003664.5(AP3B1):c.237_238del (p.Phe80fs)Pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2024→ Residue 80
NM_003664.5(AP3B1):c.395G>C (p.Arg132Pro)Likely pathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2024→ Residue 132
NM_003664.4(AP3B1):c.1839_1842delTAGAPathogenic
Hermansky-Pudlak syndrome 2
★☆☆☆2024
View on ClinVar ↗
Related Genes
AP4M1Protein interaction100%AP4E1Protein interaction100%STX11Protein interaction99%HPS4Protein interaction94%HPS3Protein interaction93%HPS5Protein interaction83%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
84%
Heart
78%
Lung
76%
Ovary
52%
Liver
40%
Gene Interaction Network
Click a node to explore
AP3B1AP4M1AP4E1STX11HPS4HPS3HPS5
PROTEIN STRUCTURE
Preparing viewer…
PDB9C5C · 3.60 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.45 [0.35–0.59]
RankingsWhere AP3B1 stands among ~20K protein-coding genes
  • #2,591of 20,598
    Most Researched170 · top quartile
  • #1,007of 5,498
    Most Pathogenic Variants73 · top quartile
  • #3,998of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedAP3B1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Pediatric hemophagocytic lymphohistiocytosis.
PMID: 32107531
Blood · 2020
1.00
2
PMID: 20301464
0.90
3
AP3B1 facilitates PDIA3/ERP57 function to regulate rabies virus glycoprotein selective degradation and viral entry.
PMID: 39128851
Autophagy · 2024
0.80
4
Congenital neutropenia.
PMID: 20008220
Hematology Am Soc Hematol Educ Program · 2009
0.70
5
Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants.
PMID: 38644452
Immunol Res · 2024
0.64