DHCR24

Chr 1AR

24-dehydrocholesterol reductase

Also known as: DCE, Nbla03646, SELADIN1, seladin-1

NCBI Gene: 1718ENSG00000116133UniProt: Q15392

This gene encodes a flavin adenine dinucleotide (FAD)-dependent oxidoreductase which catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. The protein contains a leader sequence that directs it to the endoplasmic reticulum membrane. Missense mutations in this gene have been associated with desmosterolosis. Also, reduced expression of the gene occurs in the temporal cortex of Alzheimer disease patients and overexpression has been observed in adrenal gland cancer cells. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

DesmosterolosisMIM #602398
AR
188
ClinVar variants
3
Pathogenic / LP
0.03
pLI score
2
Active trials
Clinical Summary— DHCR24
🧬
Gene-Disease Validity (ClinGen)
desmosterolosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 84 VUS of 188 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.52LOEUF
pLI 0.031
Z-score 3.46
OE 0.29 (0.17–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.50Z-score
OE missense 0.76 (0.68–0.85)
232 obs / 305.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.17–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.68–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 8 / 27.6Missense obs/exp: 232 / 305.9Syn Z: 0.65

ClinVar Variant Classifications

188 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic2
VUS84
Likely Benign96
Benign1
Conflicting4
1
Pathogenic
2
Likely Pathogenic
84
VUS
96
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
2
0
2
VUS
1
77
6
0
84
Likely Benign
0
1
35
60
96
Benign
0
0
1
0
1
Conflicting
—4
Total1784560188

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DHCR24 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DHCR24-related desmosterolosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Desmosterolosis

MIM #602398

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review.
Fu X et al.·Technol Cancer Res Treat
2024Review
Cholesterol neutralized vemurafenib treatment by promoting melanoma stem-like cells via its metabolite 27-hydroxycholesterol.
Wang X et al.·Cell Mol Life Sci
2024
DHCR24 Insufficiency Promotes Vascular Endothelial Cell Senescence and Endothelial Dysfunction via Inhibition of Caveolin-1/ERK Signaling.
Li H et al.·J Gerontol A Biol Sci Med Sci
2024
DHCR24 overexpression is involved in lipid metabolic reprogramming to drive cervical cancer malignant progression and is associated with immune microenvironment.
Cheng L et al.·BMC Cancer
2025
Genkwadaphnin inhibits growth and invasion in hepatocellular carcinoma by blocking DHCR24-mediated cholesterol biosynthesis and lipid rafts formation.
Wu J et al.·Br J Cancer
2020
Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma.
Dai M et al.·Sci Rep
2017
Phenotype-genotype correlation in aldosterone-producing adenomas characterized by intracellular cholesterol metabolism.
Harashima S et al.·J Steroid Biochem Mol Biol
2022
MicroRNA-124 regulates cardiomyocyte apoptosis and myocardial infarction through targeting Dhcr24.
Han F et al.·J Mol Cell Cardiol
2019
DHCR24 predicts poor clinicopathological features of patients with bladder cancer: A STROBE-compliant study.
Liu XP et al.·Medicine (Baltimore)
2018Cohort
A variant near DHCR24 associates with microstructural properties of white matter and peripheral lipid metabolism in adolescents.
Sliz E et al.·Mol Psychiatry
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Castration-Resistant Prostate CarcinomaMetastatic Castration-Resistant Prostate CarcinomaRefractory Prostate Carcinoma

Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer

ACTIVE NOT RECRUITING
NCT05828082Phase PHASE2National Cancer Institute (NCI)Started 2023-10-16
Biopsy ProcedureBiospecimen CollectionComputed Tomography
Breast Cancer FemaleInfertility, Female

Impact of Breast Cancer on Human Folliculogenesis

ACTIVE NOT RECRUITING
NCT07148141University Hospital, Clermont-FerrandStarted 2019-01-11
Ovarian stimulation

External Resources

Links to major genomics databases and tools