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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AP3D1
adaptor related protein complex 3 subunit delta 1
Chromosome 19 · 19p13.3
NCBI Gene: 8943Ensembl: ENSG00000065000.20HGNC: HGNC:568UniProt: A0A8V8TQW4
182PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
lysosomal membraneprotein localization to membraneendosome to melanosome transportprotein bindingHermansky-Pudlak syndrome 10Hermansky-Pudlak syndromeAlzheimer diseaseneurodegenerative disease
✦AI Summary

AP3D1 encodes the delta subunit of the AP-3 adaptor complex, a non-clathrin-associated protein complex that mediates vesicle budding from the Golgi and trafficking to lysosomes and lysosome-related organelles 1. AP3D1 functions in sorting cargo proteins destined for secretory lysosomes and is essential for both ubiquitous and neuron-specific forms of the AP-3 complex 2. The protein plays critical roles in CD8+ T-cell and NK cell degranulation and synaptic vesicle transport 2. Mechanistically, AP3D1 sorts palmitoylated interferon gamma receptor 1 (IFNGR1) to lysosomes for degradation, a process regulated by optineurin; loss of this regulatory interaction drives immune evasion in colorectal cancer 3. Biallelic AP3D1 mutations cause Hermansky-Pudlak syndrome type 10 (HPS10), characterized by oculocutaneous albinism, immunodeficiency, neutropenia, seizures, neurodevelopmental delay, and platelet dysfunction 24. AP3D1 mutations represent a primary immune regulatory disorder affecting immune cell function and secretory organelle biogenesis 5. Additionally, serum anti-AP3D1 antibodies serve as atherosclerosis biomarkers associated with acute ischemic stroke risk 6. Dysregulation of AP3D1 expression has been implicated in inflammatory conditions including acute gouty arthritis and systemic autoimmune diseases 78.

Sources cited
1
AP-3 is a novel adaptor complex recruited to TGN and peripheral compartments not associated with clathrin, playing a role in sorting proteins to lysosomes
PMID: 9714795
2
AP3D1 mutations cause HPS10 with albinism, immunodeficiency, seizures, and neurologic phenotype; AP3D1 is essential for both ubiquitous and neuronal AP-3 complex forms
PMID: 26744459
3
Biallelic AP3D1 mutations cause Hermansky-Pudlak syndrome type 10 with oculocutaneous albinism, immunodeficiency, seizures, and platelet dysfunction
PMID: 30472485
4
AP3D1 binds and sorts palmitoylated IFNGR1 to lysosomes for degradation; optineurin prevents this sorting to maintain IFNγ signaling and immune function
PMID: 33627378
5
AP3D1 mutations are recognized as a cause of Primary Immune Regulatory Disorders in the IUIS classification
PMID: 38644452
6
Serum anti-AP3D1 antibodies are elevated in atherosclerosis and acute ischemic stroke, serving as risk biomarkers
PMID: 34188129
7
AP3D1 upregulation via lncRNA SNHG8-miR-542-3p axis accelerates acute gouty arthritis development
PMID: 34874227
8
AP3D1 identified as a hub gene potentially involved in systemic sclerosis and lupus erythematosus pathogenesis
PMID: 40537884
Disease Associationsⓘ21
Hermansky-Pudlak syndrome 10Open Targets
0.58Moderate
Hermansky-Pudlak syndromeOpen Targets
0.42Moderate
Alzheimer diseaseOpen Targets
0.42Moderate
lysosomal storage diseaseOpen Targets
0.42Moderate
multiple sclerosisOpen Targets
0.42Moderate
neurodegenerative diseaseOpen Targets
0.42Moderate
Parkinson diseaseOpen Targets
0.42Moderate
albinismOpen Targets
0.42Moderate
neutropeniaOpen Targets
0.42Moderate
Hermansky-Pudlak syndrome with neutropeniaOpen Targets
0.42Moderate
Decreased total neutrophil countOpen Targets
0.42Moderate
SeizureOpen Targets
0.42Moderate
blood platelet diseaseOpen Targets
0.37Weak
osteoarthritisOpen Targets
0.23Weak
renal carcinomaOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
hypertensionOpen Targets
0.19Weak
osteoarthritis, kneeOpen Targets
0.19Weak
medical procedureOpen Targets
0.14Weak
ThrombocytopeniaOpen Targets
0.14Weak
Hermansky-Pudlak syndrome 10UniProt
Pathogenic Variants1
NM_001261826.3(AP3D1):c.3565_3566del (p.Val1189fs)Pathogenic
Hermansky-Pudlak syndrome 10
☆☆☆☆2016→ Residue 1189
View on ClinVar ↗
Related Genes
AP4B1Protein interaction100%AP4M1Protein interaction100%AP4E1Protein interaction100%VPS39Protein interaction100%AP2A1Protein interaction97%AP5M1Protein interaction95%
Tissue Expression6 tissues
Liver
100%
Lung
87%
Brain
73%
Heart
70%
Ovary
69%
Bone Marrow
46%
Gene Interaction Network
Click a node to explore
AP3D1AP4B1AP4M1AP4E1VPS39AP2A1AP5M1
PROTEIN STRUCTURE
Preparing viewer…
PDB4AFI · 2.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.44Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.35 [0.27–0.44]
RankingsWhere AP3D1 stands among ~20K protein-coding genes
  • #2,376of 20,598
    Most Researched182 · top quartile
  • #4,745of 5,498
    Most Pathogenic Variants1
  • #2,430of 17,882
    Most Constrained (LOEUF)0.44 · top quartile
Genes detectedAP3D1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
PMID: 20301464
1.00
2
Loss of Optineurin Drives Cancer Immune Evasion via Palmitoylation-Dependent IFNGR1 Lysosomal Sorting and Degradation.
PMID: 33627378
Cancer Discov · 2021
0.90
3
Clathrin and adaptors.
PMID: 9714795
Biochim Biophys Acta · 1998
0.80
4
A homozygous AP3D1 missense variant in patients with sensorineural hearing loss as the leading manifestation.
PMID: 36445457
Hum Genet · 2023
0.72
5
Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants.
PMID: 38644452
Immunol Res · 2024
0.70