DHCR7 Gene: 7-Dehydrocholesterol Reductase and Smith-Lemli-Opitz Syndrome
The DHCR7 gene encodes the enzyme 7-dehydrocholesterol reductase, which catalyzes the final step of cholesterol biosynthesis. Pathogenic variants in DHCR7 cause Smith-Lemli-Opitz syndrome (SLOS), a metabolic and developmental disorder. This article provides a comprehensive overview of the DHCR7 gene, its protein function, associated diseases, expression patterns, and mutation spectrum.
Gene Information Card
| Symbol | DHCR7 |
|---|---|
| Full Name | 7-dehydrocholesterol reductase |
| Gene Type | protein coding |
| Chromosomal Location | 11q13.4 |
| NCBI Gene ID | 1717 ncbi.nlm.nih.gov/gene/1717 |
| Ensembl ID | ENSG00000172893 |
| UniProt ID | Q9UBM7 |
| OMIM ID | 602858 |
| HGNC ID | 2860 |
| Aliases | 7-DHC reductase, D7SR, SLOS |
Description
The DHCR7 gene encodes 7-dehydrocholesterol reductase (DHCR7), an integral membrane protein of the endoplasmic reticulum. This enzyme catalyzes the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol, the final and rate-limiting step in the Kandutsch-Russell pathway of cholesterol biosynthesis. Cholesterol is a critical structural component of cell membranes and a precursor for steroid hormones, bile acids, and vitamin D. Proper DHCR7 function is essential for normal embryonic development, particularly of the central nervous system and limbs. Pathogenic variants in DHCR7 lead to a deficiency in enzyme activity, resulting in the accumulation of 7-DHC and its derivatives and a concurrent deficiency of cholesterol, which underlies the pathophysiology of Smith-Lemli-Opitz syndrome (SLOS).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Smith-Lemli-Opitz Syndrome (SLOS) | Biallelic pathogenic variants in DHCR7 cause a deficiency of 7-dehydrocholesterol reductase, leading to reduced cholesterol synthesis and accumulation of 7-dehydrocholesterol (7-DHC). This disrupts embryonic development, particularly affecting the central nervous system and limb formation, resulting in the characteristic features of SLOS. | ClinVar, OMIM |
| Lathosterolosis | While primarily associated with DHCR7, defects in other enzymes of the post-squalene cholesterol biosynthesis pathway can cause similar phenotypes. However, lathosterolosis is specifically caused by mutations in the SC5D gene, not DHCR7. DHCR7 mutations are specifically linked to SLOS. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Liver | 31.2 | Medium |
| Adrenal Gland | 25.7 | Medium |
| Brain - Cerebellum | 18.9 | Low |
| Testis | 15.3 | Low |
| Small Intestine | 12.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (Liver) | 28.5 | High expression consistent with liver's role in cholesterol synthesis. |
| SH-SY5Y (Neuroblastoma) | 15.2 | Moderate expression in neuronal cells. |
| A549 (Lung) | 8.4 | Low expression in lung carcinoma cells. |
| MCF7 (Breast) | 5.1 | Low expression in breast cancer cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.964-1G>C (IVS8-1G>C) | Splice site | Common in SLOS patients (approx. 30% of alleles) | Disrupts splicing, leading to a non-functional protein and severe enzyme deficiency. |
| p.Trp151Ter (W151X) | Nonsense | Recurrent in SLOS | Introduces a premature stop codon, resulting in a truncated, non-functional protein. |
| p.Val326Leu (V326L) | Missense | Common in SLOS patients | Amino acid substitution that reduces enzyme activity, often associated with a milder phenotype. |
| p.Thr154Met (T154M) | Missense | Reported in SLOS | Substitution that impairs protein stability and catalytic function. |
| p.Arg352Trp (R352W) | Missense | Reported in SLOS | Alters the active site, leading to reduced enzyme activity. |
Mutation functional classification
Loss of Function (LOF)
The vast majority of DHCR7 pathogenic variants are loss-of-function mutations. These include nonsense, frameshift, splice-site, and missense mutations that result in reduced or absent 7-dehydrocholesterol reductase activity. This leads to the characteristic biochemical profile of SLOS: elevated 7-DHC and decreased cholesterol.
Gain of Function (GOF)
No gain-of-function mutations have been described for DHCR7. The enzyme's role is catabolic in the final step of cholesterol synthesis, and increased activity is not associated with any known pathology.
Dominant Negative (DN)
SLOS is inherited in an autosomal recessive pattern, requiring two mutant alleles. While some missense mutations may produce a protein that could theoretically interfere with the wild-type enzyme if co-expressed, the disease mechanism is primarily due to haploinsufficiency or complete loss of function in homozygous or compound heterozygous states. No clear dominant-negative effect has been established.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • 7-dehydrocholesterol reductase activity |
| • cholesterol biosynthetic process | • sterol biosynthetic process |
| • lipid metabolic process | • endoplasmic reticulum membrane |
| • integral component of membrane | • response to sterol depletion |
Pathways
• Cholesterol biosynthesis
• Metabolism of steroids
• Terpenoid backbone biosynthesis
• Metabolic pathways
Protein Summary
The DHCR7 protein is a 475-amino-acid enzyme localized to the endoplasmic reticulum membrane. It belongs to the superfamily of short-chain dehydrogenases/reductases (SDRs). The protein contains a sterol-sensing domain (SSD) that is critical for its regulation and function. DHCR7 catalyzes the reduction of the delta-7 double bond of 7-dehydrocholesterol (7-DHC) to produce cholesterol, using NADPH as a cofactor. This reaction is the final committed step in the Kandutsch-Russell pathway. The enzyme's activity is tightly regulated by cellular sterol levels; it is down-regulated by high cholesterol and up-regulated by sterol depletion via the SREBP (sterol regulatory element-binding protein) pathway. Defects in this protein lead to the accumulation of 7-DHC and a deficiency of cholesterol, which are the hallmarks of Smith-Lemli-Opitz syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DHCR7 Knockout HEK293 Cell Line | EDJ-KQ1955 | Human | 1717 | Details Get a Quote |
| DHCR7 Knockout A-549 Cell Line | EDJ-KQ23271 | Human | 1717 | Details Get a Quote |
| DHCR7 Knockout HCT 116 Cell Line | EDJ-KQ23273 | Human | 1717 | Details Get a Quote |
| DHCR7 Knockout HeLa Cell Line | EDJ-KQ23274 | Human | 1717 | Details Get a Quote |
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