AP2S1: Adaptor Related Protein Complex 2 Subunit Sigma 1
A key component of the clathrin-associated adaptor protein complex 2 (AP-2) involved in endocytosis and implicated in familial hypocalciuric hypercalcemia and other disorders.
Gene Information Card
| Symbol | AP2S1 |
|---|---|
| Full Name | Adaptor Related Protein Complex 2 Subunit Sigma 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 1175 ncbi.nlm.nih.gov/gene/1175 |
| Ensembl ID | ENSG00000142798 |
| UniProt ID | P53680 |
| OMIM ID | 602242 |
| HGNC ID | 565 |
| Aliases | AP17, CLAPS2, sigma2, AP-2 complex subunit sigma |
Description
AP2S1 encodes the sigma-1 subunit of the adaptor protein complex 2 (AP-2), which is essential for clathrin-mediated endocytosis. The AP-2 complex recognizes and binds to cargo proteins, including the calcium-sensing receptor (CaSR), facilitating their internalization from the plasma membrane. Mutations in AP2S1 disrupt CaSR endocytosis, leading to altered calcium homeostasis and familial hypocalciuric hypercalcemia type 3 (FHH3).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial hypocalciuric hypercalcemia type 3 (FHH3) | Missense mutations in AP2S1 impair the interaction of the AP-2 complex with the CaSR, reducing its endocytosis and causing increased cell-surface CaSR activity, leading to altered calcium sensing and hypercalcemia. | Multiple families and functional studies (PMID: 23352163, 23352164) |
| Hypocalciuric hypercalcemia, familial, type III | Same mechanism as FHH3; gain-of-function mutations in AP2S1 reduce CaSR internalization. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 20.1 | Medium |
| Heart | 15.3 | Medium |
| Liver | 12.8 | Medium |
| Kidney | 18.5 | Medium |
| Testis | 22.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 25.0 | High expression |
| HeLa | 18.2 | Medium expression |
| K562 | 15.6 | Medium expression |
| A549 | 14.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.44G>A (p.Arg15His) | Missense | Rare | Gain-of-function; reduces CaSR endocytosis, causing FHH3 |
| c.44G>C (p.Arg15Pro) | Missense | Rare | Gain-of-function; similar effect as p.Arg15His |
| c.46C>T (p.Arg16Cys) | Missense | Rare | Gain-of-function; associated with FHH3 |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in human disease.
Gain of Function (GOF)
Missense mutations in the AP2S1 gene (e.g., p.Arg15His, p.Arg15Pro, p.Arg16Cys) are gain-of-function, impairing CaSR internalization and leading to FHH3.
Dominant Negative (DN)
Not described for AP2S1.
View complete mutation data：
Gene Ontology (GO)
| • clathrin adaptor activity | • protein binding |
| • intracellular protein transport | • clathrin coat assembly |
| • endocytosis | • vesicle-mediated transport |
Pathways
• Clathrin-mediated endocytosis (KEGG hsa04144)
• AP-2 complex assembly
Protein Summary
AP2S1 encodes the sigma-1 subunit of the AP-2 adaptor complex. This small protein (17 kDa) is part of a heterotetrameric complex that links clathrin to cargo receptors at the plasma membrane. The sigma subunit contributes to cargo recognition and complex stability. Mutations in AP2S1 specifically affect the interaction with the calcium-sensing receptor, leading to altered calcium homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AP2S1 Knockout HEK293 Cell Line | EDJ-KQ50197 | Human | 1175 | Details Get a Quote |
| AP2S1 Knockout HeLa Cell Line | EDJ-KQ52920 | Human | 1175 | Details Get a Quote |
| AP2S1 Knockout A-549 Cell Line | EDJ-KQ61387 | Human | 1175 | Details Get a Quote |
| AP2S1 Knockout HCT 116 Cell Line | EDJ-KQ69882 | Human | 1175 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
