HCCS (gene)

The HCCS gene is located on the Xp22 region of chromosome X and encodes a protein that is ~30 kDa in size. The HCCS protein is localized to the inner mitochondrial membrane and is expressed in multiple tissue including prominently in the cardiovascular system and the central nervous system.^[6]

The HCCS protein functions as a lyase to covalently attach the heme group to the apoprotein of cytochrome c on the inner mitochondrial membrane of the mitochondrion.^[7] The heme group is required for cytochrome c to transport electrons from complex III to complex IV of the electron transport chain during respiration. Heme attachment to cytochrome c takes place in the intermembrane space and requires conserved heme-interacting residues on HCCS on one of the two heme-binding domains on HCCS, including His154.^[8] The HCCS protein may function to regulate mitochondrial lipid and total mitochondrial mass in response to mitochondrial dysfunctions.^[9]

Mutations in the HCCS gene cause microphthalmia with linear skin defects (MLS) syndrome,^[10] also known as MIDAS syndrome, microphthalmia, syndromic 7 (MCOPS7), or microphthalmia, dermal aplasia, and sclerocornea.^[11][12] MLS is a rare X-linked dominant male-lethal disease characterized by unilateral or bilateral microphthalmia and linear skin defects in affected females, and in utero lethality for affected males.^[11]