DHCR7

Chr 11AR

7-dehydrocholesterol reductase

Also known as: SLOS

This gene encodes an enzyme that removes the C(7-8) double bond in the B ring of sterols and catalyzes the conversion of 7-dehydrocholesterol to cholesterol. This gene is ubiquitously expressed and its transmembrane protein localizes to the endoplasmic reticulum membrane and nuclear outer membrane. Mutations in this gene cause Smith-Lemli-Opitz syndrome (SLOS); a syndrome that is metabolically characterized by reduced serum cholesterol levels and elevated serum 7-dehydrocholesterol levels and phenotypically characterized by cognitive disability, facial dysmorphism, syndactyly of second and third toes, and holoprosencephaly in severe cases to minimal physical abnormalities and near-normal intelligence in mild cases. Alternative splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Aug 2009]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Smith-Lemli-Opitz syndromeMIM #270400
AR

Clinical highlights

Gene-disease validity (ClinGen)
Smith-Lemli-Opitz syndrome · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
102
Pubs (1 yr)
P/LP submissions
P/LP missense
1.35
LOEUF
LOF
Mechanism· G2P
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GeneReview available — DHCR7
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.35LOEUF
pLI 0.000
Z-score 0.31
OE 0.93 (0.651.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.45Z-score
OE missense 1.07 (0.981.18)
322 obs / 300.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.93 (0.651.35)
00.351.4
Missense OE?1.07 (0.981.18)
00.61.4
Synonymous OE?1.21
01.21.6
LoF obs/exp: 20 / 21.5Missense obs/exp: 322 / 300.0Syn Z: -1.88

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DHCR7 · protein map & ClinVar variants

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