Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

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Lerner-Ellis JP, Tirone JC, Pawelek PD, Dore C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS

Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

Nat Genet. 2006 Jan;38(1):93-100. Epub 2005 Nov 27.

PubMed ID

16311595 [ View in PubMed

]

Abstract

Methylmalonic aciduria and homocystinuria, cblC type (OMIM 277400), is the most common inborn error of vitamin B(12) (cobalamin) metabolism, with about 250 known cases. Affected individuals have developmental, hematological, neurological, metabolic, ophthalmologic and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. The cblC locus was mapped to chromosome region 1p by linkage analysis. We refined the chromosomal interval using homozygosity mapping and haplotype analyses and identified the MMACHC gene. In 204 individuals, 42 different mutations were identified, many consistent with a loss of function of the protein product. One mutation, 271dupA, accounted for 40% of all disease alleles. Transduction of wild-type MMACHC into immortalized cblC fibroblast cell lines corrected the cellular phenotype. Molecular modeling predicts that the C-terminal region of the gene product folds similarly to TonB, a bacterial protein involved in energy transduction for cobalamin uptake.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cyanocobalamin	Methylmalonic aciduria and homocystinuria type C protein	Protein	Humans	Unknown	Cofactor	Details
Hydroxocobalamin	Methylmalonic aciduria and homocystinuria type C protein	Protein	Humans	Unknown	Other/unknown	Details

Polypeptides

Name	UniProt ID
Methylmalonic aciduria and homocystinuria type C protein	Q9Y4U1	Details