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Gene Review

GDAP1  -  ganglioside induced differentiation...

Homo sapiens

Synonyms: CMT4, CMT4A, CMTRIA, Ganglioside-induced differentiation-associated protein 1
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Disease relevance of GDAP1


High impact information on GDAP1


Biological context of GDAP1

  • Mutations in GDAP1 lead to severe forms of the peripheral motor and sensory neuropathy, Charcot-Marie-Tooth disease (CMT), which is characterized by heterogeneous phenotypes, including pronounced axonal damage and demyelination [6].
  • GDAP1-specific knockdown by RNA interference results in a tubular mitochondrial morphology [6].
  • The latter activity also is reduced strongly for disease-associated GDAP1 point mutations [6].
  • We report four additional families with recessive mutations (487C-->T, Q163X; 359G-->A, R120Q) of GDAP1; Q163X occurred in three unrelated Hispanic families that had the same haplotype suggesting a Spanish founder mutation [7].
  • In this study, we identified two novel mutations disrupting the GDAP1 reading frame [3].

Anatomical context of GDAP1

  • GDAP1 truncations that are found in patients who have CMT are not targeted to mitochondria and have lost mitochondrial fragmentation activity [6].
  • Our data indicate that an exquisitely tight control of mitochondrial dynamics, regulated by GDAP1, is crucial for the proper function of myelinated peripheral nerves [6].
  • One subgroup designated CMT4 type A (CMT4A) was selected from a series of Tunisian CMT4 families according to the following electrophysiological and pathological criteria: slow motor nerve conduction velocity (MCV), severe hypomyelination upon nerve biopsy with basal lamina onion bulbs and no myelin outfolding [8].
  • Only in a few CMT4A affected patients sural nerve biopsy findings have been provided [9].

Associations of GDAP1 with chemical compounds

  • The protein encoded by GDAP1 shows clear similarity to glutathione transferases (also known as glutathione S-transferases or GSTs) [10].
  • Thus, GDAP derivatives provide versatile new tools for biologists to quantify and covalently capture minute quantities of glycans for exploring their structures and functions and generating new glycan arrays from naturally occurring glycans [11].

Other interactions of GDAP1

  • The human genome contains a paralog of GDAP1 called GDAP1L1 [10].
  • Traditionally, the different classes of CMT have been divided into demyelinating forms (CMT1, CMT3, and CMT4) and axonal forms (CMT2), a clinically very useful distinction [12].
  • In GDAP1 and DNM2 mutants, both Schwann cells and axons/neurons might be directly affected [13].
  • In addition, using SSCP and our physical map, we have demonstrated that the myelin protein PMP-2, mapped by FISH to this region, is not the defect in CMT4A [14].

Analytical, diagnostic and therapeutic context of GDAP1


  1. The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. Cuesta, A., Pedrola, L., Sevilla, T., García-Planells, J., Chumillas, M.J., Mayordomo, F., LeGuern, E., Marín, I., Vílchez, J.J., Palau, F. Nat. Genet. (2002) [Pubmed]
  2. GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is expressed in neurons and is associated with mitochondria. Pedrola, L., Espert, A., Wu, X., Claramunt, R., Shy, M.E., Palau, F. Hum. Mol. Genet. (2005) [Pubmed]
  3. Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy. Senderek, J., Bergmann, C., Ramaekers, V.T., Nelis, E., Bernert, G., Makowski, A., Züchner, S., De Jonghe, P., Rudnik-Schöneborn, S., Zerres, K., Schröder, J.M. Brain (2003) [Pubmed]
  4. Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene. Azzedine, H., Ruberg, M., Ente, D., Gilardeau, C., Périé, S., Wechsler, B., Brice, A., LeGuern, E., Dubourg, O. Neuromuscul. Disord. (2003) [Pubmed]
  5. Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21. Baxter, R.V., Ben Othmane, K., Rochelle, J.M., Stajich, J.E., Hulette, C., Dew-Knight, S., Hentati, F., Ben Hamida, M., Bel, S., Stenger, J.E., Gilbert, J.R., Pericak-Vance, M.A., Vance, J.M. Nat. Genet. (2002) [Pubmed]
  6. Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease. Niemann, A., Ruegg, M., La Padula, V., Schenone, A., Suter, U. J. Cell Biol. (2005) [Pubmed]
  7. CMT4A: identification of a Hispanic GDAP1 founder mutation. Boerkoel, C.F., Takashima, H., Nakagawa, M., Izumo, S., Armstrong, D., Butler, I., Mancias, P., Papasozomenos, S.C., Stern, L.Z., Lupski, J.R. Ann. Neurol. (2003) [Pubmed]
  8. Linkage of a locus (CMT4A) for autosomal recessive Charcot-Marie-Tooth disease to chromosome 8q. Ben Othmane, K., Hentati, F., Lennon, F., Ben Hamida, C., Blel, S., Roses, A.D., Pericak-Vance, M.A., Ben Hamida, M., Vance, J.M. Hum. Mol. Genet. (1993) [Pubmed]
  9. Early onset Charcot-Marie-Tooth disease caused by a homozygous Leu239Phe mutation in the GDAP1 gene. Kabzinska, D., Drac, H., Rowinska-Marcinska, K., Fidzianska, A., Kochanskii, A., Hausmanowa-Petrusewicz, I. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases. (2006) [Pubmed]
  10. Evolutionary and structural analyses of GDAP1, involved in Charcot-Marie-Tooth disease, characterize a novel class of glutathione transferase-related genes. Marco, A., Cuesta, A., Pedrola, L., Palau, F., Marín, I. Mol. Biol. Evol. (2004) [Pubmed]
  11. Versatile fluorescent derivatization of glycans for glycomic analysis. Xia, B., Kawar, Z.S., Ju, T., Alvarez, R.A., Sachdev, G.P., Cummings, R.D. Nat. Methods (2005) [Pubmed]
  12. Molecular cell biology of Charcot-Marie-Tooth disease. Berger, P., Young, P., Suter, U. Neurogenetics (2002) [Pubmed]
  13. Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Niemann, A., Berger, P., Suter, U. Neuromolecular Med. (2006) [Pubmed]
  14. Physical and genetic mapping of the CMT4A locus and exclusion of PMP-2 as the defect in CMT4A. Othmane, K.B., Loeb, D., Hayworth-Hodgte, R., Hentati, F., Rao, N., Roses, A.D., Ben Hamida, M., Pericak-Vance, M.A., Vance, J.M. Genomics (1995) [Pubmed]
  15. Vocal cord and diaphragm paralysis, as clinical features of a French family with autosomal recessive Charcot-Marie-Tooth disease, associated with a new mutation in the GDAP1 gene. Stojkovic, T., Latour, P., Viet, G., de Seze, J., Hurtevent, J.F., Vandenberghe, A., Vermersch, P. Neuromuscul. Disord. (2004) [Pubmed]
  16. Functional characterisation of ganglioside-induced differentiation-associated protein 1 as a glutathione transferase. Shield, A.J., Murray, T.P., Board, P.G. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  17. Differential regulation of gene expression by ovariectomy in mouse aorta. Villablanca, A.C., Lewis, K.A., Tham, D., Rutledge, J.C. Physiol. Genomics (2003) [Pubmed]
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