DHCR24 Gene (24-Dehydrocholesterol Reductase): Function, Disease Associations, and Clinical Significance
Comprehensive guide to DHCR24, the gene encoding 24-dehydrocholesterol reductase, its role in cholesterol biosynthesis, mutations, expression, and related disorders.
Gene Information Card
| Symbol | DHCR24 |
|---|---|
| Full Name | 24-dehydrocholesterol reductase |
| Gene Type | protein-coding |
| Chromosomal Location | 1p32.3 |
| NCBI Gene ID | 1718 ncbi.nlm.nih.gov/gene/1718 |
| Ensembl ID | ENSG00000116133 |
| UniProt ID | Q15392 |
| OMIM ID | 606418 |
| HGNC ID | 2859 |
| Aliases | DCE, Nbla03646, SELADIN1, seladin-1 |
Description
The DHCR24 gene encodes 24-dehydrocholesterol reductase, an enzyme localized to the endoplasmic reticulum that catalyzes the final step of cholesterol biosynthesis, converting desmosterol to cholesterol. This enzyme also possesses antioxidant properties and has been implicated in protection against oxidative stress and apoptosis. Mutations in DHCR24 cause desmosterolosis, a rare autosomal recessive disorder characterized by multiple congenital anomalies and developmental delay. Additionally, reduced DHCR24 expression is observed in the brain of Alzheimer's disease patients, suggesting a role in neurodegeneration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Desmosterolosis | Loss-of-function mutations in DHCR24 lead to accumulation of desmosterol and deficient cholesterol synthesis, disrupting membrane formation and signaling. | OMIM 602398; ClinVar; multiple case reports. |
| Alzheimer's disease | Reduced DHCR24 expression in affected brain regions may impair cholesterol homeostasis and increase oxidative stress, contributing to neurodegeneration. | Studies show decreased DHCR24 mRNA in Alzheimer's brains (e.g., Greeve et al., 2000). |
| Congenital anomalies (e.g., microcephaly, cardiac defects) | Impaired cholesterol biosynthesis during development due to DHCR24 mutations leads to structural malformations. | OMIM 602398; case reports. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | High | High expression (nTPM ~ 100) |
| Liver | High | High expression (nTPM ~ 80) |
| Brain | Moderate | Moderate expression (nTPM ~ 30) |
| Testis | Moderate | Moderate expression (nTPM ~ 25) |
| Lung | Low | Low expression (nTPM ~ 10) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Liver cancer cell line; high DHCR24 expression. |
| SH-SY5Y | Moderate | Neuroblastoma cell line; moderate expression. |
| A549 | Low | Lung carcinoma cell line; low expression. |
| MCF7 | Moderate | Breast cancer cell line; moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly303Arg | Missense | Rare | Loss of enzyme activity; associated with desmosterolosis. |
| p.Arg443His | Missense | Rare | Reduced activity; found in desmosterolosis patients. |
| p.Trp581Leu | Missense | Rare | Loss of function; pathogenic. |
| c.1128+1G>A | Splice site | Rare | Splicing defect; leads to truncated protein. |
Mutation functional classification
Loss of Function (LOF)
Most DHCR24 mutations are loss-of-function, leading to reduced or absent enzyme activity, causing desmosterolosis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DHCR24.
Dominant Negative (DN)
No dominant-negative effects have been described; the disorder is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • cholesterol biosynthetic process |
| • endoplasmic reticulum membrane | • response to oxidative stress |
| • apoptotic process | • steroid metabolic process |
Pathways
• Cholesterol biosynthesis
• Metabolism of steroids
• SREBP signaling
Protein Summary
The DHCR24 protein is a flavin adenine dinucleotide (FAD)-dependent oxidoreductase that reduces the delta-24 double bond of sterol intermediates, converting desmosterol to cholesterol. It is a transmembrane protein located in the endoplasmic reticulum. Beyond its enzymatic role, DHCR24 acts as a protective factor against oxidative stress and apoptosis, and has been implicated in the pathogenesis of Alzheimer's disease. The protein is also known as seladin-1 (selective Alzheimer's disease indicator-1).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DHCR24 Knockout HEK293 Cell Line | EDJ-KQ4442 | Human | 1718 | Details Get a Quote |
| DHCR24 Knockout A-549 Cell Line | EDJ-KQ26995 | Human | 1718 | Details Get a Quote |
| DHCR24 Knockout HCT 116 Cell Line | EDJ-KQ26996 | Human | 1718 | Details Get a Quote |
| DHCR24 Knockout HeLa Cell Line | EDJ-KQ26997 | Human | 1718 | Details Get a Quote |
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