MCCC1

Methylcrotonoyl-CoA carboxylase subunit alpha is an enzyme that in humans is encoded by the MCCC1 gene.

Function

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.

Clinical significance

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.

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, and in neurodegenerative disease genetics, with intronic variants such as rs12637471 associated with altered gene expression and Parkinson’s disease susceptibility.