ClinGen Dosage Sensitivity Curation Page

HSD17B10

  • Curation Status: Complete

Location Information

  • Xp11.22
  • GRCh37/hg19 chrX: 53,458,206-53,461,323
  • View: NCBI | Ensembl | UCSC

GRCh37/hg19 chrX: 53,458,206-53,461,323 (NC_000023.10)

  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence available
  • Haploinsufficiency phenotype comments: Several boys have been described with a neurodegenerative symptoms ascribed to MHBD deficiency (OMIM: 300438, 300220) who have missense mutations in HSD17B10. Some females with mutations are normal and others have milder symptoms. All mutations described have been missense, except for one which is a silent mutation that causes aberrant splicing in a percentage of transcripts. Animal models suggest that complete loss of this gene is embryonic lethal in males. The HSD10 protein has multiple enzymatic functions and is critical for mitochondrial function. It was originally thought that clinical symptoms were due to loss of enzyme activity. However, there is no correlation between disease severity and enzyme activity. There have been no loss of function mutations described and the mechanism of disease is not understood. See Zschocke et al (2012, PMID: 22127393) for a recent literature review and Rauschenberger et al (2010, PMID: 20077426) for recent work on possible disease mechanisms related to enzyme activity. Previous cases with missense mutations are reviewed by Zschocke and include PMIDs: 17236142, 12696021, 19706438, 17618155, 22132097, 20664630.

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 score: 0
  • Strength of Evidence (disclaimer): No evidence available
  • Triplosensitivity phenotype comment: There have been no focal duplications of HSD17B10. One group reported 6 families with X-linked mental retardation with a duplication that included HSD17B10 and other genes (Froyen, 2008, PMID: 18252223), OMIM: 300705. However, additional analysis of 6 more families with overlapping duplications showed that the minimally overlapping region for all 12 families did not include HSD17B10 but rather was specific to HUWE1 (Froyen, 2012, PMID:22840365).

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.