- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_02
,
released June 18, 2026
This report describes Charcot-Marie-Tooth disease, recessive intermediate D (CMTRID), which is a subtype of Charcot-Marie-Tooth disease; CMTRID is inherited as an autosomal recessive. The human gene implicated in this disease is cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), a subunit of the terminal enzyme of the mitochondrial respiratory chain. The fly gene Dmel\levy is a high-scoring ortholog of COX6A1; a classical loss-of-function allele for levy, RNAi-targeting constructs, and an allele caused by insertional mutagenesis have been generated. There are additional orthologous genes in both species. Other disease model reports for diseases that impact mitochondrial complex IV are listed in the report 'mitochondrial complex IV deficiency' (FBhh0000363).
A UAS construct of the wild-type human Hsap\COX6A1 gene has been introduced into flies, but has not been characterized.
A loss-of-function mutation in the Dmel\levy gene, when homozygous or hemizygous (over deficiency) results in reduced life span, progressive neurodegeneration, and temperature-sensitive paralysis. Physical interactions of the levy protein product have been described; see below and in the FlyBase gene report for Dmel\levy.
[updated Apr. 2020 by FlyBase; FBrf0222196]
Charcot-Marie-Tooth disease (CMT) constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies. CMT is divided into several major types: Type 1 is characterized by demyelination and by a significantly slowed motor median nerve conduction velocity (NCV). Type 2 is characterized by axonal abnormalities and a normal or slightly reduced NCV. "Intermediate" types describe CMT families with nerve conduction velocities, in different affected individuals, that overlap the division between Type 1 and Type 2. Additional types are defined on the basis inheritance patterns. [from MIM:609260 and MIM:606482; 2015.12.15]
Symptoms typically include progressive distal muscle weakness and atrophy, often associated with mild to moderate sensory loss, depressed tendon reflexes, and high-arched feet. [from Gene Reviews, http://www.ncbi.nlm.nih.gov/books/NBK1358 2015.12.15]
[CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE D; CMTRID](https://omim.org/entry/616039)
[CYTOCHROME c OXIDASE, SUBUNIT 6A1; COX6A1](https://omim.org/entry/602072)
See description of different CMT classification types, above.
CMTRID is inherited as an autosomal recessive and appears to be caused by homozygous mutation in the COX6A1 gene; based on limited sample (3 patients from 2 unrelated consanguineous families). [from MIM:616039; 2016.01.20]
COX6A1 is a subunit of cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain. [from MIM:602072; 2016.01.20]
Ortholog of human genes COX6A1, COX6A2 and COX6A1P2 (3 Drosophila to 3 human). High-scoring ortholog of COX6A1 (reciprocal best hit). Dmel\levy shares 48% identity and 62% similarity with COX6A1; the two proteins are of identical length.