NSDHL

Chr XXLDXLR

NAD(P) dependent 3-beta-hydroxysteroid dehydrogenase NSDHL

Also known as: H105E3, SDR31E1, XAP104

The protein catalyzes NAD(P)(+)-dependent oxidative decarboxylation of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis and regulates endocytic trafficking of EGFR. Mutations cause CHILD syndrome and CK syndrome through X-linked dominant inheritance, with the condition typically being lethal in males due to disrupted cholesterol biosynthesis. The gene shows high constraint against loss-of-function variants, suggesting mutations predominantly cause disease through haploinsufficiency.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLD/XLRLOEUF 0.292 OMIM phenotypes
Clinical SummaryNSDHL
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Gene-Disease Validity (ClinGen)
CK syndrome · XLModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
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GeneReview available — NSDHL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.964
Z-score 2.98
OE 0.00 (0.000.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.87Z-score
OE missense 0.80 (0.690.93)
124 obs / 154.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.29)
00.351.4
Missense OE0.80 (0.690.93)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 0 / 10.3Missense obs/exp: 124 / 154.4Syn Z: -1.02

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NSDHL · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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