NSDHL gene

The NSDHL gene (NSDHL stands for: NAD(P) Dependent Steroid Dehydrogenase-Like) is a protein coding gene located on chromosome Xq28. Associated pathways include the cholesterol biosynthesis superpathway and cholesterol metabolism, and an important paralog of this gene is SDR42E1.

The protein encoded by this gene, a 3beta-hydroxysteroid dehydrogenase, catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4-methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis. It also plays a role in the regulation of endocytic trafficking of EGFR.

3beta-hydroxysteroid dehydrogenase is localized in the endoplasmic reticulum and is involved in cholesterol biosynthesis. Mutations in this gene are associated with CHILD syndrome, an X-linked dominant disorder of lipid metabolism with impaired cholesterol biosynthesis, which is usually fatal in males (König A et al. 2000).

missense variant in the NSDHL gene can also cause inflammatory linear verrucous epidermal nevi in dogs (Leuthard F et al. 2019).

1. Caldas H et al. (2005) Placental defects are associated with male lethality in bare patches and striated embryos deficient in the NAD(P)H steroid dehydrogenase-like (NSDHL) enzyme. Mol Genet Metab 84:48-60.

2. Christen M et al. (2020) NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi. Genes (Basel) 11:1297.

3. Hettiarachchi D et al. (2020) Novel variant in NSDHL gene associated with CHILD syndrome and syndactyly- a case report. BMC Med Genet 21:164.
4. König A et al. (2000) Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet 90:339-346.
5. Maceda EBG et al. (2020) Novel NSDHL gene variant for congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome. BMJ Case Rep 13:e236859.
6. Zhuang J et al. (2023) Etiological identification of recurrent male fatality due to a novel NSDHL gene mutation using trio whole-exome sequencing: A rare case report and literature review. Mol Genet Genomic Med 11:e2121.