HMOX2 Gene - Heme Oxygenase 2: Function, Expression, and Clinical Significance

HMOX2 (heme oxygenase 2) encodes an enzyme that catalyzes the rate-limiting step in heme degradation, cleaving heme to produce biliverdin, carbon monoxide (CO), and ferrous iron. HO-2 is constitutively expressed in many tissues, particularly in the brain, testes, and vascular endothelium, and plays key roles in cellular protection against oxidative stress, regulation of vascular tone, and neurotransmission. Unlike the inducible HO-1 isoform, HO-2 is primarily regulated by developmental and tissue-specific factors.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Heme degradation (Reactome: R-HSA-189483)

• Carbon monoxide signaling (Reactome: R-HSA-1237044)

• Bilirubin metabolism (KEGG: map00860)

Heme oxygenase 2 (HO-2) is a 36 kDa protein composed of 288 amino acids. It contains a heme-binding pocket with two conserved histidine residues (His45 and His84) that coordinate the heme iron. HO-2 also possesses two C-terminal membrane-binding domains that anchor it to the endoplasmic reticulum. The enzyme uses NADPH-cytochrome P450 reductase as an electron donor to cleave heme into biliverdin, CO, and iron. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. HO-2 is constitutively expressed and is particularly abundant in the brain, testes, and endothelial cells, where it modulates neurotransmission, vascular tone, and antioxidant defense.