NSDHL

Gene Facts

• HGNC Symbol: NSDHL (HGNC:13398)
• HGNC Name: NAD(P) dependent steroid dehydrogenase-like
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: No previous names found
• Alias symbols: XAP104, H105e3, SDR31E1
• %HI: 64.89
• pLI: 0.96
• LOEUF: 0.29
• Cytoband: Xq28
• Genomic Coordinates:

  GRCh37/hg19:	chrX:151999607-152038273
  GRCh38/hg38:	chrX:152831063-152869729

• MANE Select Transcript: NM_015922.3 ENST00000370274.8
• Function: Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis (By similarity). Also plays a role in the regulation of the endocytic trafficking of EGFR (By similarity). {ECO:0000250|UniProtKB:Q9R1J0}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-647
• ClinGen Curation ID: CCID:007581
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Sufficient Evidence for Haploinsufficiency (3)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 09/25/2019

Haploinsufficiency (HI) Score Details

• HI Score: 3
• HI Evidence Strength: Sufficient Evidence for Haploinsufficiency

HI Disease

• CHILD syndrome

• HI Evidence Comments: The NSDHL-related disorders include: CHILD (Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects) syndrome, an X-linked dominant condition that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked recessive disorder that affects males. Complete loss of function mutations are generally associated with CHILD syndrome whereas CK syndrome is generally associated with hypomorphic (partial loss of function) mutations. Female carriers of mutations associated with CK syndrome (hypomorphic alleles) generally have have normal physical features, intellect and brain imaging but may display behavioral problems such as irritability and aggression. Some examples of the documented loss of function variants include: Bornholdt (2015), 3 cases, +0.3 c.208C>T p.Q70* c.894G>A p.W298* c.906C>A p.Y302* Konig (2000), 2 cases, +0.2 c.262C>T p.R88* c.628C>T p.Q210* Hummel (2003), +0.1 c.451G>T p.E151* Danarti (2010), +0.1 c.766C>T p.R256* Estapé (2015), +0.1 c.357_358delAG p.Arg119Serfs*1d Yu (2018), +0.1 ex. 3-4 del Yang (2015), 2 cases, +0.1 ex. 4-7 del

NOTE

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity
• TS Evidence Comments: At this time, there are no reported focal whole gene duplications of NSDHL.

NOTE

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.