AP1S2
Adaptor Related Protein Complex 1 Subunit Sigma 2
Gene Information Card
| Symbol | AP1S2 |
|---|---|
| Full Name | Adaptor Related Protein Complex 1 Subunit Sigma 2 |
| Gene Type | protein-coding |
| Chromosomal Location | Xp22.2 |
| NCBI Gene ID | 8905 ncbi.nlm.nih.gov/gene/8905 |
| Ensembl ID | ENSG00000182287 |
| UniProt ID | P56377 |
| OMIM ID | 300629 |
| HGNC ID | 560 |
| Aliases | AP1S2, sigma1B, AP-1 complex subunit sigma-2, clathrin coat assembly protein AP1S2 |
Description
AP1S2 encodes the sigma-2 subunit of the adaptor protein complex 1 (AP-1), which is involved in clathrin-coated vesicle trafficking between the trans-Golgi network and endosomes. The sigma subunit is essential for AP-1 complex assembly and cargo recognition. Mutations in AP1S2 cause X-linked intellectual disability with or without Petitgrew syndrome, characterized by developmental delay, seizures, and dysmorphic features.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability, Hedera type | Loss-of-function mutations impair AP-1 complex function, disrupting intracellular trafficking and neuronal development | OMIM #300423 |
| Petitgrew syndrome | Missense or nonsense mutations in AP1S2 lead to defective vesicle transport, causing intellectual disability, seizures, and dysmorphic features | OMIM #304340 |
| X-linked intellectual disability with seizures | Disruption of AP-1-mediated trafficking affects synaptic vesicle recycling and neuronal signaling | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Low |
| Kidney | 6.1 | Low |
| Liver | 4.3 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.0 | Neuronal model |
| HEK293 (embryonic kidney) | 10.2 | Common expression |
| HeLa (cervical carcinoma) | 7.8 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | Rare | Loss of start codon, likely loss of function |
| c.346C>T (p.Arg116*) | nonsense | Rare | Premature stop, loss of function |
| c.400G>A (p.Gly134Arg) | missense | Rare | Disrupts sigma subunit folding and AP-1 complex assembly |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent protein, impairing AP-1 complex function.
Gain of Function (GOF)
No evidence of gain-of-function mutations in AP1S2.
Dominant Negative (DN)
Missense mutations may produce a defective sigma subunit that disrupts AP-1 complex assembly, potentially acting in a dominant-negative manner in hemizygous males.
View complete mutation data：
Gene Ontology (GO)
| • clathrin adaptor activity | • intracellular protein transport |
| • vesicle-mediated transport | • Golgi to endosome transport |
| • protein complex assembly |
Pathways
• Clathrin-mediated endocytosis
• AP-1 complex-mediated transport
• Intracellular vesicle trafficking
Protein Summary
AP1S2 encodes the sigma-2 subunit of the AP-1 complex, a heterotetramer that links clathrin to cargo proteins in vesicle trafficking. The sigma subunit stabilizes the complex and contributes to cargo specificity. The protein is highly expressed in brain, consistent with its role in neuronal function. Mutations cause X-linked intellectual disability by disrupting trafficking of synaptic proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AP1S2 Knockout HEK293 Cell Line | EDJ-KQ50829 | Human | 8905 | Details Get a Quote |
| AP1S2 Knockout HeLa Cell Line | EDJ-KQ55030 | Human | 8905 | Details Get a Quote |
| AP1S2 Knockout A-549 Cell Line | EDJ-KQ63516 | Human | 8905 | Details Get a Quote |
| AP1S2 Knockout HCT 116 Cell Line | EDJ-KQ71982 | Human | 8905 | Details Get a Quote |
