NSDHL

Chr XXLDXLR

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

Also known as: H105E3, SDR31E1, XAP104

NCBI Gene: 50814 ENSG00000147383 UniProt: Q15738 OMIM: 300275

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is localized in the endoplasmic reticulum and is involved in cholesterol biosynthesis. Mutations in this gene are associated with CHILD syndrome, which is a X-linked dominant disorder of lipid metabolism with disturbed cholesterol biosynthesis, and typically lethal in males. Alternatively spliced transcript variants with differing 5' UTR have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

CHILD syndromeMIM #308050

XLD

CK syndromeMIM #300831

XLR

UniProtCongenital hemidysplasia with ichthyosiform erythroderma and limb defects

Clinical highlights

Gene-disease validity (ClinGen)

CK syndrome · XLModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — NSDHL