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FB2026_01
,
released March 12, 2026
This report describes neuronopathy, distal hereditary motor, X-linked (HMNX), one of several diseases associated with the human ATP7A; HMNX exhibits sex-linked recessive inheritance. ATP7A encodes Cu(2+)-transporting ATPase, alpha polypeptide, a transmembrane copper-transporting P-type ATPase. There is one high-scoring ortholog in Drosophila, ATP7, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated. ATP7A is associated with several other diseases, Menkes disease (MIM:309400, FBhh0000076) and occipital horn syndrome (MIM:304150, FBhh0000078). Dmel\ATP7 is also orthologous to a paralogous gene in human, ATP7B.
Multiple UAS constructs of the human Hsap\ATP7A gene have been introduced into flies, including wild-type and a variant implicated in disease (see FBhh0000438). ATP7B has not been introduced into flies.
The human disease model report for copper metabolism disorders, ATP7-related (FBhh0000438) describes experimental results using Drosophila models of ATP7-related diseases that affect copper levels and transport. However, in the case of HMNX, a role in copper metabolism has not been established.
Using the fly gene Dmel\ATP7, a variant analogous to one specifically implicated in HMNX has been characterized and has been shown to act like a partial loss-of-function mutation. See the 'Disease-Implicated Variants' table below.
[updated Feb. 2024 by FlyBase; FBrf0222196]
[NEURONOPATHY, DISTAL HEREDITARY MOTOR, X-LINKED; HMNX](https://omim.org/entry/300489)
[ATPase, Cu(2+)-TRANSPORTING, ALPHA POLYPEPTIDE; ATP7A](https://omim.org/entry/300011)
X-linked distal spinal muscular atrophy (ATP7A-related distal motor neuropathy) is a disorder of copper transport caused by mutations in the copper-transporting ATPase gene (ATP7A). ATP7A-related distal motor neuropathy, an adult-onset disorder resembling Charcot-Marie-Tooth disease, shares none of the clinical or biochemical abnormalities characteristic of Menkes disease or occipital horn syndrome. [from GeneReviews, ATP7A-Related Copper Transport Disorders, pubmed:20301586 2015.12.18]
HMNX is a distal form of distal muscular atrophy affecting both the upper and lower limbs; weakness of the lower limbs results in gait abnormalities and atrophy of lower limb muscles. Disease progression is typically very slow. There is little or no sensory involvement in affected individuals. (Takata, et al, 2004, pubmed:14985388; Kennerson et al., 2009, pubmed:19153371). [from MIM:300489; 2024.02.20]
X-linked distal hereditary motor neuronopathy (HMNX) is caused by mutation in the copper transport gene ATP7A; recessive inheritance is observed. [from MIM:300489; 2024.02.20]
The ATP7A gene encodes a transmembrane copper-transporting P-type ATPase, Cu(2+)-transporting ATPase, alpha polypeptide. P-type ATPases are a family of integral membrane proteins that use an aspartylphosphate intermediate to transport cations across membranes. The 1,500-residue ATP7A protein was found to have the characteristics of a copper-binding protein. It has 6 N-terminal copper binding sites and a catalytic transduction core with several functional domains (Vulpe et al., 1993, pubmed:8490659). [From MIM:300011 and MIM:304150, 2015.12.18]
Many to one: 2 human to 1 Drosophila.
High-scoring ortholog of human genes ATP7A and ATP7B (1 Drosophila to 2 human). Dmel\ATP7 shares 46-47% identity and 62% similarity with human genes.