NSDHL
NAD(P) Dependent Steroid Dehydrogenase-Like Gene in Cholesterol Biosynthesis and Developmental Disorders
Gene Information Card
| Symbol | NSDHL |
|---|---|
| Full Name | NAD(P) Dependent Steroid Dehydrogenase-Like |
| Gene Type | Protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 50814 ncbi.nlm.nih.gov/gene/50814 |
| Ensembl ID | ENSG00000147383 |
| UniProt ID | Q15738 |
| OMIM ID | 300275 |
| HGNC ID | 13398 |
| Aliases | H105E3, SDR31E1, XAP104 |
Description
NSDHL encodes a 3β-hydroxysteroid dehydrogenase involved in the cholesterol biosynthesis pathway, specifically catalyzing the decarboxylation of 4α-carboxysterols. Mutations in this gene cause CK syndrome (X-linked intellectual disability with seizures) and CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects). The gene is located on the X chromosome and escapes X-inactivation in some tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| CK syndrome | Loss-of-function mutations impair cholesterol synthesis, leading to neuronal dysfunction and intellectual disability | ClinVar, OMIM #300831 |
| CHILD syndrome | Deficiency in NSDHL disrupts cholesterol biosynthesis, causing asymmetric limb and skin abnormalities | ClinVar, OMIM #308050 |
| X-linked intellectual disability | NSDHL mutations reduce sterol intermediates, affecting brain development | OMIM #300275 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Brain | 8.3 | Low |
| Liver | 15.2 | Medium |
| Skin | 10.1 | Medium |
| Testis | 18.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.3 | Hepatocellular carcinoma cell line |
| SH-SY5Y | 9.8 | Neuroblastoma cell line |
| HaCaT | 11.2 | Keratinocyte cell line |
| MCF7 | 7.5 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109G>A (p.Gly37Arg) | Missense | Rare | Loss of enzymatic activity; associated with CK syndrome |
| c.325C>T (p.Arg109*) | Nonsense | Rare | Premature truncation; CHILD syndrome |
| c.674A>G (p.Asn225Ser) | Missense | Rare | Reduced protein stability; intellectual disability |
Mutation functional classification
Loss of Function (LOF)
Most NSDHL mutations are loss-of-function, reducing or abolishing 3β-hydroxysteroid dehydrogenase activity, leading to accumulation of toxic sterol intermediates and impaired cholesterol synthesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NSDHL.
Dominant Negative (DN)
No dominant-negative effects have been described; mutations are typically hemizygous in males or subject to X-inactivation patterns in females.
View complete mutation data：
Gene Ontology (GO)
| • 3β-hydroxy-Δ5-steroid dehydrogenase activity (GO:0003854) | • cholesterol biosynthetic process (GO:0006695) |
| • sterol biosynthetic process (GO:0016126) | • endoplasmic reticulum (GO:0005783) |
| • cytoplasm (GO:0005737) |
Pathways
• Cholesterol biosynthesis (KEGG: hsa00100)
• Metabolism of steroids (Reactome: R-HSA-8957322)
• Terpenoid backbone biosynthesis (KEGG: hsa00900)
Protein Summary
NSDHL is a 373-amino acid protein localized to the endoplasmic reticulum. It functions as a NAD(P)-dependent 3β-hydroxysteroid dehydrogenase, catalyzing the decarboxylation of 4α-carboxysterols (e.g., 4α-carboxy-4β-methyl-5α-cholesta-8,24-dien-3β-ol) during cholesterol biosynthesis. The protein contains a conserved short-chain dehydrogenase/reductase (SDR) domain. Defects in NSDHL lead to accumulation of toxic sterol intermediates, particularly in the brain and skin, explaining the neurological and dermatological phenotypes in associated disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NSDHL Knockout HEK293 Cell Line | EDJ-KQ10817 | Human | 50814 | Details Get a Quote |
| NSDHL Knockout HCT 116 Cell Line | EDJ-KQ37179 | Human | 50814 | Details Get a Quote |
| NSDHL Knockout A-549 Cell Line | EDJ-KQ38470 | Human | 50814 | Details Get a Quote |
| NSDHL Knockout HeLa Cell Line | EDJ-KQ38471 | Human | 50814 | Details Get a Quote |
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