DHCR7
Function
Catalyzes the last step of the cholesterol synthesis pathway, which transforms cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol,7-DHC) into cholesterol by reducing the C7-C8 double bond of its sterol core (PubMed:25637936, PubMed:38297129, PubMed:38297130, PubMed:9465114, PubMed:9634533). Can also metabolize cholesta-5,7,24-trien-3beta-ol (7-dehydrodemosterol, 7-DHD) to desmosterol, which is then metabolized by the Delta(24)-sterol reductase (DHCR24) to cholesterol (By similarity). Modulates ferroptosis (a form of regulated cell death driven by iron-dependent lipid peroxidation) through the metabolic breakdown of the anti-ferroptotic metabolites 7-DHC and 7-DHD which, when accumulated, divert the propagation of peroxyl radical-mediated damage from phospholipid components to its sterol core, protecting plasma and mitochondrial membranes from phospholipid autoxidation (PubMed:38297129, PubMed:38297130).
Involvement in disease
Smith-Lemli-Opitz syndrome
SLOS
An autosomal recessive frequent inborn disorder of sterol metabolism with characteristic congenital malformations and intellectual disability. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and low serum cholesterol levels. SLOS occurs in relatively high frequency: approximately 1 in 20,000 to 30,000 births in populations of northern and central European background. Historically, a clinical distinction often was made between classic ('type I') SLOS and the more severely affected ('type II') patients. There is, in reality, a clinical and biochemical continuum from mild to severe SLOS.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Steroid biosynthesis; cholesterol biosynthesis.
Sequence Similarities
Belongs to the ERG4/ERG24 family.
Tissue Specificity
Widely expressed. Most abundant in adrenal gland, liver, testis, and brain.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
D7SR, DHCR7, 7-dehydrocholesterol reductase, 7-DHC reductase, Delta7-sterol reductase, Sterol Delta(7)-reductase, Sterol reductase SR-2