Normal Function
The MCCC1 gene provides instructions for making one part (the alpha subunit) of an enzyme called 3-methylcrotonoyl-CoA carboxylase or MCC. These alpha subunits join with smaller beta subunits made from the MCCC2 gene; six of these pairings together form a functioning enzyme. The alpha subunit also includes a region for binding to the B vitamin biotin, which is required for the enzyme to function.
The MCC enzyme is found in mitochondria, which are the energy-producing centers inside cells. This enzyme plays a critical role in breaking down proteins obtained from food. Specifically, it is responsible for the fourth step in the breakdown of leucine, an amino acid that is a building block of many proteins. This step converts a molecule called 3-methylcrotonyl-CoA to a molecule called 3-methylglutaconyl-CoA. Additional chemical reactions convert 3-methylglutaconyl-CoA into molecules that are later used for energy.
Health Conditions Related to Genetic Changes
3-methylcrotonyl-CoA carboxylase deficiency
Many variants (also called mutations) in the MCCC1 gene have been identified in people with 3-methylcrotonyl-CoA carboxylase deficiency (also called MCC deficiency). MCC deficiency is an inherited disorder in which the body is unable to process certain proteins properly. Most of these variants change single amino acids in MCC, but a few lead to the production of an abnormally short version of the enzyme. Variants in the MCCC1 gene severely reduce or eliminate the activity of MCC. As a result, leucine cannot be broken down properly, and byproducts of leucine processing can build up in the body. Some people with these genetic changes will show signs and symptoms of MCC deficiency.
More About This Health ConditionOther Names for This Gene
- 3-methylcrotonyl-CoA carboxylase 1
- 3-methylcrotonyl-CoA carboxylase alpha
- 3-methylcrotonyl-CoA carboxylase biotin-containing subunit
- MCCA
- MCCase subunit alpha
- MCCCalpha
- MCCCα
- methylcrotonoyl-CoA carboxylase 1
- methylcrotonoyl-CoA carboxylase 1 alpha
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Baumgartner MR, Almashanu S, Suormala T, Obie C, Cole RN, Packman S, Baumgartner ER, Valle D. The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency. J Clin Invest. 2001 Feb;107(4):495-504. doi: 10.1172/JCI11948. Citation on PubMed or Free article on PubMed Central
- Dantas MF, Suormala T, Randolph A, Coelho D, Fowler B, Valle D, Baumgartner MR. 3-Methylcrotonyl-CoA carboxylase deficiency: mutation analysis in 28 probands, 9 symptomatic and 19 detected by newborn screening. Hum Mutat. 2005 Aug;26(2):164. doi: 10.1002/humu.9352. Citation on PubMed
- Desviat LR, Perez-Cerda C, Perez B, Esparza-Gordillo J, Rodriguez-Pombo P, Penalva MA, Rodriguez De Cordoba S, Ugarte M. Functional analysis of MCCA and MCCB mutations causing methylcrotonylglycinuria. Mol Genet Metab. 2003 Nov;80(3):315-20. doi: 10.1016/S1096-7192(03)00130-6. Citation on PubMed
- Gallardo ME, Desviat LR, Rodriguez JM, Esparza-Gordillo J, Perez-Cerda C, Perez B, Rodriguez-Pombo P, Criado O, Sanz R, Morton DH, Gibson KM, Le TP, Ribes A, de Cordoba SR, Ugarte M, Penalva MA. The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism. Am J Hum Genet. 2001 Feb;68(2):334-46. doi: 10.1086/318202. Epub 2001 Jan 17. Citation on PubMed or Free article on PubMed Central
- Grunert SC, Stucki M, Morscher RJ, Suormala T, Burer C, Burda P, Christensen E, Ficicioglu C, Herwig J, Kolker S, Moslinger D, Pasquini E, Santer R, Schwab KO, Wilcken B, Fowler B, Yue WW, Baumgartner MR. 3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals. Orphanet J Rare Dis. 2012 May 29;7:31. doi: 10.1186/1750-1172-7-31. Citation on PubMed
- Holzinger A, Roschinger W, Lagler F, Mayerhofer PU, Lichtner P, Kattenfeld T, Thuy LP, Nyhan WL, Koch HG, Muntau AC, Roscher AA. Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency. Hum Mol Genet. 2001 Jun 1;10(12):1299-306. doi: 10.1093/hmg/10.12.1299. Citation on PubMed
- Obata K, Fukuda T, Morishita R, Abe S, Asakawa S, Yamaguchi S, Yoshino M, Ihara K, Murayama K, Shigemoto K, Shimizu N, Kondo I. Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene (MCCA): cDNA sequence, genomic organization, localization to chromosomal band 3q27, and expression. Genomics. 2001 Mar 1;72(2):145-52. doi: 10.1006/geno.2000.6366. Citation on PubMed
- Stadler SC, Polanetz R, Maier EM, Heidenreich SC, Niederer B, Mayerhofer PU, Lagler F, Koch HG, Santer R, Fletcher JM, Ranieri E, Das AM, Spiekerkotter U, Schwab KO, Potzsch S, Marquardt I, Hennermann JB, Knerr I, Mercimek-Mahmutoglu S, Kohlschmidt N, Liebl B, Fingerhut R, Olgemoller B, Muntau AC, Roscher AA, Roschinger W. Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment. Hum Mutat. 2006 Aug;27(8):748-59. doi: 10.1002/humu.20349. Citation on PubMed
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