ATP7A: Copper-Transporting ATPase 1
Key regulator of copper homeostasis; mutations cause Menkes disease and occipital horn syndrome
Gene Information Card
| Symbol | ATP7A |
|---|---|
| Full Name | ATPase copper transporting alpha |
| Gene Type | protein-coding |
| Chromosomal Location | Xq21.1 |
| NCBI Gene ID | 538 ncbi.nlm.nih.gov/gene/538 |
| Ensembl ID | ENSG00000165240 |
| UniProt ID | Q04656 |
| OMIM ID | 300011 |
| HGNC ID | 869 |
| Aliases | MNK, MK, ATP7A1, Cu(2+)-transporting ATPase alpha polypeptide |
Description
ATP7A encodes a transmembrane protein that transports copper across cellular membranes, playing a critical role in copper absorption from the intestine and distribution to copper-dependent enzymes. The protein is localized to the trans-Golgi network and cycles to the plasma membrane in response to elevated copper levels. Defects in ATP7A lead to Menkes disease (kinky hair syndrome) and occipital horn syndrome, both X-linked copper deficiency disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Menkes disease | Loss-of-function mutations impair copper transport, leading to systemic copper deficiency and severe neurodegeneration | ClinVar, OMIM |
| Occipital horn syndrome | Milder ATP7A mutations reduce copper transport, causing connective tissue abnormalities and bony exostoses | ClinVar, OMIM |
| ATP7A-related distal motor neuropathy | Specific missense mutations cause a late-onset peripheral neuropathy without classic Menkes features | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 15.1 | Medium |
| Small intestine | 22.4 | High |
| Placenta | 18.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocyte line |
| SH-SY5Y | 11.8 | Neuroblastoma line |
| Caco-2 | 20.5 | Intestinal epithelial line |
| HEK293 | 9.6 | Embryonic kidney line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2179G>A (p.Gly727Arg) | Missense | <0.01% | Reduced copper transport activity; Menkes disease |
| c.2938C>T (p.Arg980*) | Nonsense | <0.01% | Premature truncation; severe Menkes disease |
| c.1946_1947del (p.Leu649Argfs*2) | Frameshift | <0.01% | Loss of function; Menkes disease |
| c.4087G>A (p.Glu1363Lys) | Missense | <0.01% | Occipital horn syndrome |
Mutation functional classification
Loss of Function (LOF)
Majority of ATP7A mutations (nonsense, frameshift, splice-site) lead to complete or partial loss of copper transport, causing Menkes disease.
Gain of Function (GOF)
Not reported for ATP7A.
Dominant Negative (DN)
Not reported; ATP7A is X-linked and hemizygous in males.
View complete mutation data：
Gene Ontology (GO)
| • copper-exporting ATPase activity (GO:0004008) | • copper ion transmembrane transporter activity (GO:0005375) |
| • copper ion transport (GO:0006825) | • integral component of membrane (GO:0016021) |
| • metal ion transport (GO:0030001) | • metal ion binding (GO:0046872) |
Pathways
• Copper homeostasis (Reactome: R-HSA-437239)
• Metal ion SLC transporters (KEGG: hsa04978)
Protein Summary
ATP7A is a 1500-amino acid P-type ATPase with eight transmembrane domains, a nucleotide-binding domain, and a phosphorylation domain. It uses ATP hydrolysis to pump copper from the cytosol into the trans-Golgi lumen for incorporation into cuproenzymes. Under high copper, it relocates to the plasma membrane to export excess copper. Mutations disrupt copper delivery, leading to deficiency of copper-dependent enzymes such as lysyl oxidase and cytochrome c oxidase.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP7A Knockout HEK293 Cell Line | EDJ-KQ4115 | Human | 538 | Details Get a Quote |
| ATP7A Knockout A-549 Cell Line | EDJ-KQ26511 | Human | 538 | Details Get a Quote |
| ATP7A Knockout HCT 116 Cell Line | EDJ-KQ26512 | Human | 538 | Details Get a Quote |
| ATP7A Knockout HeLa Cell Line | EDJ-KQ26513 | Human | 538 | Details Get a Quote |
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