Gene Function

ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis. Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state. Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of the secretory pathway. Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions. May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3 (By similarity). In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (By similarity) Source: UniProt

Relationship to CMT

dSMA XLR
1 subtype
Xq21.1

First described 2010

Subtype	Inheritance	Class	OMIM	Sentinel Publication
SubtypedSMAX-3	InheritanceX-linked recessive	ClassdSMA	OMIM300489	Sentinel Publication Missense Mutations in the Copper Transporter Gene ATP7A Cause X-Linked Distal Hereditary Motor Neuropathy 2010 · 10.1016/j.ajhg.2010.01.027

Stored Identifiers

No HGNC Aliases

hgnc_idHGNC:869

ensembl_gene_idENSG00000165240

coords_grch38chrX:77910688-78050395

coords_grch37chrX:77166194-77305892

entrez_id538

omim_gene300011

uniprot_idsQ04656

refseq_accessionNM_000052

mane_refseqNM_000052.7

mane_ensemblENST00000341514.11

External recordsHGNC:869OMIM 300011gnomADUniProt Q04656ClinGenClinVar P/LPGeneReviewsOrphanetMANE NM_000052.7

EvidenceClinGen Moderate X-linked distal spinal muscular atrophy type 3PanelApp GreenClinGen dosage HI 3 · Sufficient evidence

ClinVar Variants

Pathogenic and likely pathogenic variants in ATP7A, as classified in ClinVar, are read live from NCBI. Only aggregate germline records are shown. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, one for a single submitter with criteria provided, and none where no criteria were provided.

Reported in CMT

Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

The Dorsal Root

A Name That Does Too Much Work

Jean-Martin Charcot's name appears throughout medicine, but nowhere does it create more confusion than in the foot. Learn why the CMT foot and Charcot neuroarthropathy, also known as Charcot foot, share a name yet differ in how they develop, appear, and are managed.

When Medicine Lost Its Compass

Evidence failed not because it was wrong, but because it was weaponized. I lived the downstream effects of that failure for more than a decade. This is what happens when medicine forgets that data always ends in a human being.

Error 404: Gene Not Found

CMT genetic testing often fails to identify the cause of the disease, even when comprehensive panels are used. Here, we discuss why this happens, what genetic tests can and cannot do, and why a negative result still matters.