MCCC1

MCCC1 encodes the α-subunit of the mitochondrial enzyme methylcrotonyl-CoA carboxylase (MCC), which catalyzes a key carboxylation step in the catabolic pathway of the branched-chain amino acid leucine. The MCC holoenzyme forms a dodecameric α6β6 complex in which MCCC1-derived α subunits contain the biotin-binding and carboxylation domains essential for enzymatic activity.^[5]

Pathogenic variants in MCCC1 cause 3-methylcrotonyl-CoA carboxylase deficiency, an autosomal recessive metabolic disorder characterized by impaired leucine degradation and accumulation of organic acid intermediates.^[6][7]

Beyond its metabolic role, MCCC1 has been implicated in immune regulation, where it enhances antiviral signaling through MAVS-mediated activation of NF-κB and interferon pathways,^[8] and in neurodegenerative disease genetics, with intronic variants such as rs12637471 associated with altered gene expression and Parkinson’s disease susceptibility.^[9]