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FB2026_02
,
released June 18, 2026
This report describes Charcot-Marie-Tooth disease, type 2K (CMT2K), which is a subtype of Charcot-Marie-Tooth disease. The human gene implicated in this disease is GDAP1, which is an integral membrane protein of the outer mitochondrial membrane and is found at high levels in neuronal cells. GDAP1 is implicated in several subtypes of Charcot-Marie-Tooth disease (MIM:214400, MIM:608340, MIM:607706, MIM:607831). See the report for Charcot-Marie-Tooth disease, GDAP1-related (FBhh0000092) for information on experimental results using Drosophila models of this and related diseases.
A missense mutation in the JPH1 gene has been tentatively identified as a modifier of CMT2K, causing a more severe phenotype in carriers of a GDAP1 mutation. See the report for 'neuromuscular disease, JPH-related' (FBhh0000819) for information on experimental results in Drosophila relevant to CMT2K and other JPH-related diseases.
[updated Jun. 2018 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, AXONAL, TYPE 2K; CMT2K](https://omim.org/entry/607831)
[JUNCTOPHILIN 1; JPH1](https://omim.org/entry/605266)
[GANGLIOSIDE-INDUCED DIFFERENTIATION-ASSOCIATED PROTEIN 1; GDAP1](https://omim.org/entry/606598)
See description of different CMT classification types, above.
CMT2K shows both autosomal recessive and autosomal dominant patterns of inheritance; it has been shown to be caused by mutation in the GDAP1 gene. [from MIM:607831; 2015.12.17]
A missense mutation in the JPH1 gene has been tentatively identified as a modifier of CMT2K, causing a more severe phenotype in carriers of a GDAP1 mutation. [from MIM:607831; 2018.06.21]
GDAP1 is an integral membrane protein of the outer mitochondrial membrane; it is expressed in the central and peripheral nervous system (Niemann et al., 2005; pubmed:16172208). The C-terminal transmembrane domains are necessary for correct localization in mitochondria; 5 disease-causing missense mutations assayed did not alter mitochondrial localization (Pedrola et al. 2005; pubmed:15772096). [from MIM:606598; 2015.12.17]
Many to one: 2 human to 1 Drosophila; the second orthologous human gene is GDAP1L1.