AP4S1
Adaptor Related Protein Complex 4 Subunit Sigma 1
Gene Information Card
| Symbol | AP4S1 |
|---|---|
| Full Name | Adaptor Related Protein Complex 4 Subunit Sigma 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q12 |
| NCBI Gene ID | 11154 ncbi.nlm.nih.gov/gene/11154 |
| Ensembl ID | ENSG00000100478 |
| UniProt ID | Q9Y587 |
| OMIM ID | 607243 |
| HGNC ID | 574 |
| Aliases | AP47B, HSPAP4S1, sigma4, SPG52 |
Description
The AP4S1 gene encodes the sigma subunit of the adaptor protein complex 4 (AP-4), which is involved in intracellular vesicle trafficking, particularly the sorting of transmembrane proteins from the trans-Golgi network to endosomes or the plasma membrane. Mutations in AP4S1 cause autosomal recessive hereditary spastic paraplegia type 52 (SPG52), a neurodevelopmental and neurodegenerative disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia 52 (SPG52) | Loss-of-function mutations impair AP-4 complex assembly, disrupting neuronal protein trafficking and leading to axonal degeneration. | OMIM #614067; ClinVar; multiple case reports |
| AP-4 Deficiency Syndrome | Biallelic AP4S1 mutations cause a syndromic form of hereditary spastic paraplegia with intellectual disability, microcephaly, and epilepsy. | OMIM; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.9 | Medium |
| Lung | 6.2 | Low |
| Liver | 4.1 | Low |
| Kidney | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.2 | Neuroblastoma cell line |
| HEK293 | 7.8 | Embryonic kidney cells |
| HeLa | 6.5 | Cervical carcinoma cells |
| U-87 MG | 9.1 | Glioblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of protein expression; causes SPG52 |
| c.130C>T (p.Arg44*) | Nonsense | Rare | Premature stop; loss of function |
| c.208_209del (p.Leu70Valfs*12) | Frameshift | Rare | Truncated protein; loss of function |
| c.337C>T (p.Arg113Trp) | Missense | Rare | Impaired AP-4 complex assembly |
Mutation functional classification
Loss of Function (LOF)
Most AP4S1 mutations are loss-of-function (nonsense, frameshift, start loss), leading to reduced or absent sigma4 subunit and defective AP-4 complex.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • intracellular protein transport | • vesicle-mediated transport |
| • protein localization to plasma membrane | • AP-4 adaptor complex |
| • clathrin adaptor activity |
Pathways
• AP-4 complex-mediated protein sorting
• Intracellular vesicle trafficking
Protein Summary
The AP4S1 protein (sigma4 subunit) is a component of the heterotetrameric AP-4 complex. It is essential for the recognition and sorting of cargo proteins containing tyrosine-based sorting signals. The sigma subunit stabilizes the complex and contributes to cargo binding. Loss of AP4S1 disrupts AP-4 function, leading to mislocalization of proteins such as ATG9A and AMPA receptors, contributing to neuronal dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AP4S1 Knockout HEK293 Cell Line | EDJ-KQ51047 | Human | 11154 | Details Get a Quote |
| AP4S1 Knockout HeLa Cell Line | EDJ-KQ55586 | Human | 11154 | Details Get a Quote |
| AP4S1 Knockout A-549 Cell Line | EDJ-KQ64083 | Human | 11154 | Details Get a Quote |
| AP4S1 Knockout HCT 116 Cell Line | EDJ-KQ72533 | Human | 11154 | Details Get a Quote |
