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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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AP3S1
adaptor related protein complex 3 subunit sigma 1
Chromosome 5 · 5q22.3-q23.1
NCBI Gene: 1176Ensembl: ENSG00000177879.17HGNC: HGNC:2013UniProt: F5H459
88PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
AP-3 adaptor complexprotein bindingvesicle-mediated transportanterograde synaptic vesicle transportneurodegenerative diseaselysosomal storage diseasealcohol drinkingfrozen shoulder
✦AI Summary

AP3S1 encodes the sigma subunit of the adaptor protein complex 3 (AP-3), which facilitates vesicle-mediated transport from the Golgi to lysosomes and other cellular compartments. The protein functions in intracellular trafficking pathways essential for proper cellular transport processes 1. AP3S1 plays a critical role in melanocyte pigmentation, as demonstrated by zebrafish studies showing that partial knockdown of Ap3s1 sensitizes melanocytes to hypopigmentation under low-copper conditions 1. The gene shows significant disease relevance across multiple cancer types. In ovarian cancer, AP3S1 emerged as a key tumor driver gene, with knockdown experiments demonstrating its regulatory role in tumor cell migration and invasion through the TGF-β/SMAD pathway 2. AP3S1 mutations are also recurrently found in HPV-associated sinonasal squamous cell carcinoma 34. Additionally, AP3S1 variants (rs3756555) are associated with increased type 2 diabetes susceptibility in Chinese populations 5. Clinically, AP3S1 expression serves as a prognostic predictor in lung adenocarcinoma, where it promotes cell growth and migration, and is associated with immune infiltration levels 6. Notably, AP3S1 expression is frequently downregulated in cervical carcinomas, with decreased expression observed in 26% of tumors 7.

Sources cited
1
AP3S1 functions in intracellular trafficking pathways and is essential for melanocyte pigmentation under copper-deficient conditions
PMID: 20713646
2
AP3S1 is a tumor driver gene in ovarian cancer that regulates cell migration and invasion through TGF-β/SMAD pathway
PMID: 38609993
3
AP3S1 shows recurrent mutations in HPV-associated sinonasal squamous cell carcinoma
PMID: 40500270
4
AP3S1 mutations are found in HPV-associated sinonasal squamous cell carcinoma
PMID: 38979305
5
AP3S1 variants are associated with increased type 2 diabetes susceptibility in Chinese populations
PMID: 20512086
6
AP3S1 serves as a prognostic predictor in lung adenocarcinoma and promotes cell growth and migration
PMID: 36524130
7
AP3S1 expression is downregulated in 26% of cervical carcinomas
PMID: 17125464
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.56Moderate
lysosomal storage diseaseOpen Targets
0.37Weak
alcohol drinkingOpen Targets
0.28Weak
frozen shoulderOpen Targets
0.27Weak
spondylolisthesisOpen Targets
0.25Weak
neoplasmOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.07Suggestive
MODYOpen Targets
0.06Suggestive
diabetes mellitus, permanent neonatal 4Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.05Suggestive
diabetes mellitus, transient neonatal, 3Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 13Open Targets
0.04Suggestive
permanent neonatal diabetes mellitus 1Open Targets
0.04Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.04Suggestive
hyperproinsulinemiaOpen Targets
0.04Suggestive
Glycogen storage disease due to hepatic glycogen synthase deficiencyOpen Targets
0.04Suggestive
glycogen storage disorder due to hepatic glycogen synthase deficiencyOpen Targets
0.04Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
scoliosisOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AP4B1Protein interaction100%AP4M1Protein interaction100%AP4E1Protein interaction100%AP5Z1Protein interaction97%AP5M1Protein interaction95%AP5S1Protein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
45%
Ovary
42%
Liver
40%
Heart
35%
Lung
30%
Gene Interaction Network
Click a node to explore
AP3S1AP4B1AP4M1AP4E1AP5Z1AP5M1AP5S1
PROTEIN STRUCTURE
Preparing viewer…
PDB9C5C · 3.60 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.43LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.77 [0.43–1.43]
RankingsWhere AP3S1 stands among ~20K protein-coding genes
  • #5,399of 20,598
    Most Researched88
  • #14,730of 17,882
    Most Constrained (LOEUF)1.43
Genes detectedAP3S1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Functional analysis and validation of oncodrive gene AP3S1 in ovarian cancer through filtering of mutation data from whole-exome sequencing.
PMID: 38609993
Eur J Med Res · 2024
1.00
2
Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma.
PMID: 40500270
Nat Commun · 2025
0.90
3
Variants in KCNQ1, AP3S1, MAN2A1, and ALDH7A1 and the risk of type 2 diabetes in the Chinese Northern Han population: a case-control study and meta-analysis.
PMID: 20512086
Med Sci Monit · 2010
0.80
4
Vesicle-mediated transport-related genes are prognostic predictors and are associated with tumor immunity in lung adenocarcinoma.
PMID: 36524130
Front Immunol · 2022
0.70
5
Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma.
PMID: 38979305
bioRxiv · 2024
0.60