ATP8A1: A P4-ATPase Flippase Involved in Phospholipid Asymmetry
Comprehensive gene card for ATP8A1, including expression, mutations, and associated diseases.
Gene Information Card
| Symbol | ATP8A1 |
|---|---|
| Full Name | ATPase phospholipid transporting 8A1 |
| Gene Type | protein-coding |
| Chromosomal Location | 4p14 |
| NCBI Gene ID | 10396 ncbi.nlm.nih.gov/gene/10396 |
| Ensembl ID | ENSG00000124406 |
| UniProt ID | Q9Y2Q0 |
| OMIM ID | 609542 |
| HGNC ID | 13531 |
| Aliases | ATPIA, ATPASEII, ATPASEIIA, hATP8A1 |
Description
ATP8A1 encodes a member of the P4-ATPase subfamily, which functions as a phospholipid flippase that translocates phosphatidylserine and phosphatidylethanolamine from the outer to the inner leaflet of cellular membranes. This activity is essential for maintaining membrane lipid asymmetry, influencing vesicle budding, cell signaling, and apoptosis. ATP8A1 is widely expressed, with highest levels in brain, testis, and kidney.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability | Loss-of-function mutations in ATP8A1 impair phospholipid asymmetry in neurons, disrupting synaptic vesicle cycling and neurotransmission. | ClinVar; PMID: 27535533 |
| Autism spectrum disorder | Rare missense variants may alter flippase activity, affecting neuronal membrane dynamics and contributing to ASD risk. | ClinVar; PMID: 25363760 |
| Cancer (multiple types) | Altered ATP8A1 expression in breast, lung, and colorectal cancers; potential role in tumor cell migration and invasion via membrane remodeling. | COSMIC; PMID: 29127120 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.5 | High |
| Testis | 15.2 | High |
| Kidney | 12.1 | Medium |
| Liver | 8.3 | Medium |
| Heart | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.4 | High expression in embryonic kidney cells |
| SH-SY5Y | 19.8 | Neuronal cell line; relevant for neurological studies |
| HeLa | 14.1 | Cervical cancer cell line |
| MCF7 | 11.3 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76Trp) | Missense | <0.01% | Reduced flippase activity; associated with intellectual disability |
| c.1045G>A (p.Gly349Ser) | Missense | <0.01% | Impaired ATP binding; linked to autism spectrum disorder |
| c.1876_1877del (p.Leu626fs) | Frameshift | <0.01% | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt catalytic domains lead to loss of flippase activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in ATP8A1.
Dominant Negative (DN)
Missense mutations that impair ATP binding or catalytic activity may exert dominant-negative effects by forming inactive complexes.
View complete mutation data：
Gene Ontology (GO)
| • phospholipid-translocating ATPase activity (GO:0004012) | • plasma membrane (GO:0005886) |
| • phospholipid transport (GO:0015914) | • phospholipid scrambling (GO:0017121) |
| • phospholipid translocation (GO:0045332) |
Pathways
• Phospholipid transport (Reactome: R-HSA-1483226)
• Maintenance of membrane lipid asymmetry (Reactome: R-HSA-5365859)
Protein Summary
ATP8A1 is a 120 kDa P4-ATPase that forms a heterodimer with CDC50A (TMEM30A) to catalyze ATP-dependent translocation of aminophospholipids from the exoplasmic to the cytoplasmic leaflet. It contains ten transmembrane domains and a large cytoplasmic loop with ATP-binding and phosphorylation sites. The protein is essential for generating and maintaining membrane asymmetry, which is critical for endocytosis, exocytosis, and cell polarity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP8A1 Knockout HEK293 Cell Line | EDJ-KQ7033 | Human | 10396 | Details Get a Quote |
| ATP8A1 Knockout HCT 116 Cell Line | EDJ-KQ31789 | Human | 10396 | Details Get a Quote |
| ATP8A1 Knockout HeLa Cell Line | EDJ-KQ31790 | Human | 10396 | Details Get a Quote |
| ATP8A1 Knockout A-549 Cell Line | EDJ-KQ63879 | Human | 10396 | Details Get a Quote |
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