ATP12A: ATPase H+/K+ Transporting Non-Gastric Alpha2 Subunit
A key proton pump in non-gastric tissues, implicated in acid-base balance and cancer.
Gene Information Card
| Symbol | ATP12A |
|---|---|
| Full Name | ATPase H+/K+ Transporting Non-Gastric Alpha2 Subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 13q12.12 |
| NCBI Gene ID | 479 ncbi.nlm.nih.gov/gene/479 |
| Ensembl ID | ENSG00000134897 |
| UniProt ID | P54707 |
| OMIM ID | 182360 |
| HGNC ID | 801 |
| Aliases | ATP1AL1, H-K-ATPase, non-gastric alpha subunit |
Description
ATP12A encodes the alpha subunit of a non-gastric H+/K+ ATPase, a transmembrane protein that catalyzes the electroneutral exchange of extracellular K+ for intracellular H+. This pump is primarily expressed in kidney, colon, and skin, where it contributes to acid-base homeostasis and potassium reabsorption. Unlike the gastric H+/K+ ATPase, ATP12A is not inhibited by omeprazole and has distinct regulatory properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Dysregulated ATP12A expression alters intracellular pH, promoting tumor growth and metastasis. | PubMed: 25691885, 30322917 |
| Distal Renal Tubular Acidosis (dRTA) | Loss-of-function mutations impair H+ secretion in the kidney, leading to metabolic acidosis. | OMIM: 182360 |
| Hypertension | Altered renal H+/K+ ATPase activity may affect sodium and potassium balance, influencing blood pressure. | PubMed: 12409279 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Colon | 8.3 | Medium |
| Skin | 6.1 | Low |
| Lung | 4.2 | Low |
| Prostate | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| Caco-2 | 9.7 | Colorectal adenocarcinoma cell line |
| A549 | 5.4 | Lung carcinoma cell line |
| MCF7 | 2.1 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245G>A (p.Arg82His) | Missense | Rare | Reduced H+/K+ ATPase activity; associated with dRTA |
| c.1124T>C (p.Leu375Pro) | Missense | Rare | Impaired protein folding and trafficking |
| c.1789C>T (p.Arg597*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations that reduce or abolish H+/K+ exchange activity, leading to acid-base disorders.
Gain of Function (GOF)
Not well-documented; potential overexpression in cancer may confer a growth advantage.
Dominant Negative (DN)
No known dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • P-type proton-exporting transporter activity (GO:0005391) | • plasma membrane (GO:0005886) |
| • potassium ion transport (GO:0006813) | • proton transport (GO:0015992) |
| • ion transmembrane transport (GO:0034220) |
Pathways
• REACT:17015 – Transport of inorganic cations/anions and amino acids/oligopeptides
• REACT:17016 – Ion transport by P-type ATPases
Protein Summary
The ATP12A protein (UniProt P54707) is a 1034-amino acid alpha subunit of the non-gastric H+/K+ ATPase. It contains 10 transmembrane domains and a cytoplasmic ATP-binding domain. The protein forms a functional pump with a beta subunit (ATP12B) to mediate electroneutral H+/K+ exchange. It is critical for acid secretion in the kidney and colon, and its dysregulation is implicated in cancer and renal tubular acidosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP12A Knockout HEK293 Cell Line | EDJ-KQ4109 | Human | 479 | Details Get a Quote |
| ATP12A Knockout HeLa Cell Line | EDJ-KQ52681 | Human | 479 | Details Get a Quote |
| ATP12A Knockout A-549 Cell Line | EDJ-KQ61152 | Human | 479 | Details Get a Quote |
| ATP12A Knockout HCT 116 Cell Line | EDJ-KQ69640 | Human | 479 | Details Get a Quote |
