AP1S3 Gene
Adaptor Related Protein Complex 1 Subunit Sigma 3
Gene Information Card
| Symbol | AP1S3 |
|---|---|
| Full Name | Adaptor Related Protein Complex 1 Subunit Sigma 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q36.1 |
| NCBI Gene ID | 130340 ncbi.nlm.nih.gov/gene/130340 |
| Ensembl ID | ENSG00000152056 |
| UniProt ID | Q96PC3 |
| OMIM ID | 615570 |
| HGNC ID | 24016 |
| Aliases | AP1S3, sigma-3, sigma3A, AP-1 complex subunit sigma-3 |
Description
AP1S3 encodes the sigma-3 subunit of the adaptor protein complex 1 (AP-1), which is involved in clathrin-dependent vesicle trafficking between the trans-Golgi network and endosomes. The sigma subunit is essential for the assembly and stability of the AP-1 complex. Mutations in AP1S3 are associated with autosomal recessive forms of pustular psoriasis and pityriasis rubra pilaris, highlighting its role in skin homeostasis and immune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pustular psoriasis | Loss-of-function mutations impair AP-1 complex function, disrupting vesicle trafficking and leading to aberrant inflammatory signaling in keratinocytes. | OMIM #616106; ClinVar |
| Pityriasis rubra pilaris | Homozygous or compound heterozygous mutations in AP1S3 cause a subtype of this disorder, likely through defective protein sorting and immune dysregulation. | OMIM #616107; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.3 | Medium |
| Lung | 8.7 | Low |
| Spleen | 6.5 | Low |
| Testis | 5.2 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.0 | High expression relevant to skin biology |
| HEK293 | 9.8 | Moderate expression |
| HeLa | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.97C>T (p.Arg33Trp) | Missense | Rare | Loss of function; disrupts AP-1 complex assembly |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; prevents translation initiation |
| c.118G>A (p.Gly40Arg) | Missense | Rare | Likely loss of function; impairs protein stability |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations in AP1S3 are loss-of-function, leading to reduced or absent sigma-3 protein, destabilizing the AP-1 complex and impairing vesicle trafficking.
Gain of Function (GOF)
No gain-of-function mutations have been reported for AP1S3.
Dominant Negative (DN)
No dominant-negative mutations have been described for AP1S3.
View complete mutation data：
Gene Ontology (GO)
| • intracellular protein transport (GO:0006886) | • vesicle-mediated transport (GO:0016192) |
| • AP-1 adaptor complex (GO:0030121) | • intracellular membrane-bounded organelle (GO:0043231) |
Pathways
• Clathrin-mediated endocytosis (KEGG: hsa04144)
• AP-1 complex assembly and function (Reactome: R-HSA-421837)
Protein Summary
The AP1S3 protein (sigma-3 subunit) is a small (22 kDa) component of the heterotetrameric AP-1 adaptor complex. It is critical for the structural integrity of the complex and for recognizing sorting signals on cargo proteins. The protein is ubiquitously expressed but shows higher levels in skin, consistent with the tissue-specific disease phenotypes. Defects in AP1S3 lead to mislocalization of transmembrane proteins and altered cytokine signaling, contributing to inflammatory skin disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AP1S3 Knockout HEK293 Cell Line | EDJ-KQ9236 | Human | 130340 | Details Get a Quote |
| AP1S3 Knockout HeLa Cell Line | EDJ-KQ34581 | Human | 130340 | Details Get a Quote |
| AP1S3 Knockout A-549 Cell Line | EDJ-KQ35820 | Human | 130340 | Details Get a Quote |
| AP1S3 Knockout HCT 116 Cell Line | EDJ-KQ35821 | Human | 130340 | Details Get a Quote |
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