ATP11C: A P4-ATPase Phospholipid Flippase with Roles in B-Cell Development and Iron Homeostasis
Comprehensive gene card for ATP11C, including genomic context, expression, disease associations, and functional classification.
Gene Information Card
| Symbol | ATP11C |
|---|---|
| Full Name | ATPase phospholipid transporting 11C |
| Gene Type | protein-coding |
| Chromosomal Location | Xq27.1 |
| NCBI Gene ID | 286410 ncbi.nlm.nih.gov/gene/286410 |
| Ensembl ID | ENSG00000101974 |
| UniProt ID | Q8NB49 |
| OMIM ID | 300516 |
| HGNC ID | 13555 |
| Aliases | ATPIF, ATP11C, ATPase, Class VI, Type 11C |
Description
ATP11C encodes a P4-ATPase (flippase) that translocates phospholipids from the exoplasmic to the cytoplasmic leaflet of cellular membranes. It is essential for B-cell development, erythroid maturation, and systemic iron homeostasis. Mutations in ATP11C cause X-linked intellectual disability with anemia and B-cell lymphopenia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability with anemia and B-cell lymphopenia | Loss-of-function mutations impair phospholipid asymmetry, disrupting B-cell receptor signaling and erythroid differentiation | OMIM #300516; PMID: 25728773 |
| Non-syndromic X-linked intellectual disability | Missense variants reduce flippase activity, affecting neuronal membrane dynamics | ClinVar; PMID: 25728773 |
| Iron-refractory iron deficiency anemia (IRIDA) | Defective ATP11C in hepatocytes impairs hepcidin regulation, leading to iron malabsorption | PMID: 25728773 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Bone marrow | 6.7 | Low |
| Whole blood | 3.1 | Low |
| Brain | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte cell line |
| K562 | 9.8 | Erythroleukemia cell line |
| Raji | 7.4 | B-cell lymphoma line |
| SH-SY5Y | 4.1 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1771C>T (p.Arg591*) | Nonsense | Rare | Loss of function; truncation of C-terminal domain |
| c.2140G>A (p.Gly714Arg) | Missense | Rare | Reduced flippase activity; associated with intellectual disability |
| c.2992C>T (p.Arg998Cys) | Missense | Rare | Impaired ATP binding; dominant-negative effect suspected |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg591*) lead to complete loss of flippase activity, causing severe B-cell and erythroid defects.
Gain of Function (GOF)
No gain-of-function mutations reported in ATP11C.
Dominant Negative (DN)
Missense variants (e.g., p.Arg998Cys) may interfere with dimerization or ATP hydrolysis, exerting dominant-negative effects in heterozygous females.
View complete mutation data：
Gene Ontology (GO)
| • phospholipid-translocating ATPase activity (GO:0004012) | • phospholipid transport (GO:0015914) |
| • plasma membrane (GO:0005886) | • trans-Golgi network membrane (GO:0030140) |
| • B-cell lineage commitment (GO:0002327) | • cellular iron ion homeostasis (GO:0006879) |
Pathways
• REACT:111045 (Phospholipid translocation)
• REACT:21376 (B-cell receptor signaling)
• REACT:111046 (Iron uptake and transport)
Protein Summary
ATP11C is a 1,132-amino acid P4-ATPase with 10 transmembrane domains and a cytoplasmic ATP-binding domain. It catalyzes ATP-dependent flipping of phosphatidylserine and phosphatidylethanolamine, maintaining membrane asymmetry. In B-cells, it supports receptor signaling; in hepatocytes, it regulates hepcidin expression. The protein is ubiquitously expressed but enriched in liver and spleen.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP11C Knockout HEK293 Cell Line | EDJ-KQ12487 | Human | 286410 | Details Get a Quote |
| ATP11C Knockout A-549 Cell Line | EDJ-KQ40161 | Human | 286410 | Details Get a Quote |
| ATP11C Knockout HCT 116 Cell Line | EDJ-KQ41448 | Human | 286410 | Details Get a Quote |
| ATP11C Knockout HeLa Cell Line | EDJ-KQ41449 | Human | 286410 | Details Get a Quote |
