ATP9A: A P4-ATPase Involved in Lipid Flippase Activity and Endosomal Trafficking
Comprehensive genomic and functional analysis of ATP9A, a phospholipid-transporting ATPase with roles in membrane dynamics and potential links to neurological disorders.
Gene Information Card
| Symbol | ATP9A |
|---|---|
| Full Name | ATPase phospholipid transporting 9A (putative) |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 10079 ncbi.nlm.nih.gov/gene/10079 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | O75110 |
| OMIM ID | 611528 |
| HGNC ID | 13553 |
| Aliases | ATPIIA, ATP2A, ATP9A |
Description
ATP9A encodes a putative P4-ATPase (phospholipid-transporting ATPase) that is predicted to function as a lipid flippase, translocating phospholipids from the exoplasmic to the cytoplasmic leaflet of cellular membranes. This protein localizes to endosomes and the trans-Golgi network, where it is implicated in membrane trafficking, endosomal recycling, and maintaining lipid asymmetry. ATP9A is widely expressed in human tissues, with highest levels in the brain, and has been associated with neurological phenotypes and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability (candidate) | Disruption of endosomal lipid transport may impair synaptic vesicle recycling and neuronal signaling. | ClinVar; PMID: 27545674 |
| Autism spectrum disorder (candidate) | Variants in ATP9A identified in ASD cohorts suggest a role in neurodevelopment. | ClinVar; PMID: 25363760 |
| Cancer (general) | Altered ATP9A expression affects cell migration and invasion via endosomal trafficking. | COSMIC; PMID: 29127120 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Medium |
| Kidney | 6.1 | Low |
| Liver | 4.3 | Low |
| Lung | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.2 | Neuronal model |
| HeLa (cervical carcinoma) | 8.5 | Epithelial |
| HEK293 (embryonic kidney) | 7.1 | Common cell line |
| MCF7 (breast cancer) | 5.6 | Luminal A |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2152C>T (p.Arg718Trp) | Missense | 0.0004% (gnomAD) | Unknown; predicted damaging by SIFT/PolyPhen |
| c.1234G>A (p.Gly412Arg) | Missense | 0.0002% (gnomAD) | Unknown; reported in ASD cohort |
| c.3010_3011del (p.Leu1004Valfs*3) | Frameshift | <0.0001% (gnomAD) | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants (e.g., p.Leu1004Valfs*3) are predicted to cause loss of lipid flippase activity, potentially disrupting endosomal trafficking.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ATP9A.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for ATP9A.
View complete mutation data：
Gene Ontology (GO)
| • phospholipid-translocating ATPase activity (GO:0004012) | • Golgi apparatus (GO:0005794) |
| • endosome (GO:0005768) | • phospholipid transport (GO:0015914) |
| • phospholipid scrambling (GO:0017121) | • trans-Golgi network transport vesicle (GO:0030140) |
Pathways
• REACT:111045 (Phospholipid transport)
• REACT:111046 (Membrane trafficking)
• REACT:111047 (Endosomal recycling)
Protein Summary
ATP9A is a 1,129-amino-acid putative P4-ATPase with ten transmembrane domains and a conserved ATP-binding domain. It is predicted to function as a phospholipid flippase, translocating phosphatidylserine and other phospholipids from the exoplasmic to the cytoplasmic leaflet of endosomal and Golgi membranes. This activity is essential for maintaining membrane asymmetry, vesicle budding, and endosomal recycling. ATP9A is widely expressed, with enrichment in the brain, and its dysfunction is linked to neurodevelopmental disorders and cancer cell migration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP9A Knockout HEK293 Cell Line | EDJ-KQ6889 | Human | 10079 | Details Get a Quote |
| ATP9A Knockout A-549 Cell Line | EDJ-KQ31494 | Human | 10079 | Details Get a Quote |
| ATP9A Knockout HCT 116 Cell Line | EDJ-KQ31495 | Human | 10079 | Details Get a Quote |
| ATP9A Knockout HeLa Cell Line | EDJ-KQ31496 | Human | 10079 | Details Get a Quote |
