MCCC2

MCCC2 encodes the β-subunit of the mitochondrial enzyme methylcrotonoyl-CoA carboxylase (MCC), which catalyzes the biotin-dependent carboxylation of 3-methylcrotonoyl-CoA to 3-methylglutaconyl-CoA in the catabolic pathway of the branched-chain amino acid leucine. The β-subunit encoded by MCCC2 contains the carboxyltransferase domain that forms active sites at the interface of β-subunit dimers within the MCC α6β6 holoenzyme.^[6]

Pathogenic variants in MCCC2 cause 3-methylcrotonyl-CoA carboxylase deficiency, an autosomal recessive inborn error of leucine metabolism that can manifest with metabolic acidosis, developmental delay, or remain clinically asymptomatic.^{[7][8][9][10]} Beyond its metabolic role, MCCC2 has been implicated in tumorigenesis through modulation of mitochondrial dynamics, apoptosis, and energy metabolism, promoting cell proliferation and migration in prostate and colorectal cancers^[11] via pathways such as GLUD1–p38 MAPK signaling.^[12]