ATP7A (Copper-transporting ATPase 1) variants and mutations

ATP7A (also known as Copper-transporting ATPase 1) is a human protein-coding gene encoding a copper-transporting ATPase 1 protein. It delivers copper to secretory-pathway enzymes and exports excess copper from cells, making it essential for systemic copper distribution. Loss-of-function variants cause Menkes disease or occipital horn syndrome, while some hypomorphic alleles produce distal motor neuropathy. This analysis covers 1,950 ATP7A variants and mutations. Of these, 67% have computational variant effect predictions. Disease context includes Menkes disease, occipital horn syndrome, and X-linked distal spinal muscular atrophy type 3. Example ATP7A variants include D2H, D2D, and P3R.

Variant analysis overview

Gene: ATP7A
Protein: Copper-transporting ATPase 1
UniProt accession: Q04656
Organism: Homo sapiens
Variants analyzed: 1950
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 1,606 unspecified-consequence records; 180 missense variants; 9 stop-gained variants; 3 splice-region variants; 134 synonymous variants; 5 stop lost; 7 frameshift variants; 3 in-frame deletions; 1 stop retained variant; 2 substitution
Prediction scores: 1,313 variants have prediction scores (67% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Menkes disease, occipital horn syndrome, X-linked distal spinal muscular atrophy type 3, hereditary disease, distal hereditary motor neuropathy, Hirschsprung disease, Ehlers-Danlos syndrome, Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 2, Au-Kline syndrome, vitiligo, oculocutaneous albinism type 6.

Protein structure and variant hotspots

Protein features: 8 transmembrane segments; 7 domains; 16 binding sites; 19 post-translational modification sites.
Structural context: 928 variants have structural context.
PTM context: 19 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable ATP7A variants

Examples include D2H, D2D, P3R, P3Q, M5I, M5T, G6D, V7M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

ATP7A analysis run — ATP7A (1,950 variants) — completed 2026-08-19