DHCR24

Chr 1

24-dehydrocholesterol reductase

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

NCBI Gene: 1718 ENSG00000116133 UniProt: Q15392

The protein is a FAD-dependent oxidoreductase that catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis in the endoplasmic reticulum. Mutations cause desmosterolosis, a cholesterol biosynthesis disorder that typically presents in infancy with developmental delay, seizures, and distinctive facial features. The condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.52

Clinical Summary— DHCR24

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Gene-Disease Validity (ClinGen)

desmosterolosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 150 VUS of 381 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.50Z-score

OE missense 0.76 (0.68–0.85)

232 obs / 305.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.17–0.52)

0≤0.351.4

Missense OE?0.76 (0.68–0.85)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 8 / 27.6Missense obs/exp: 232 / 305.9Syn Z: 0.65

ClinVar Variant Classifications

381 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic5

VUS150

Likely Benign155

Benign41

Conflicting16

Pathogenic

Likely Pathogenic

150

VUS

155

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	2	3	0	0	5
VUS	4	99	44	3	150
Likely Benign	1	1	66	87	155
Benign	0	1	38	2	41
Conflicting	—				16
Total	7	106	148	92	369

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap DHCR24 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →