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Genetics Home Reference: your guide to understanding genetic conditions
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HSD17B10

Reviewed October 2009

What is the official name of the HSD17B10 gene?

The official name of this gene is “hydroxysteroid (17-beta) dehydrogenase 10.”

HSD17B10 is the gene's official symbol. The HSD17B10 gene is also known by other names, listed below.

What is the normal function of the HSD17B10 gene?

The HSD17B10 gene provides instructions for making an enzyme called HSD10, which is found in many areas of the body. The HSD10 enzyme is located within mitochondria, the energy-producing centers inside cells, where it has several different functions.

The HSD10 enzyme plays an important role in processing steroid hormones and fats. This enzyme also helps break down the protein building block (amino acid) isoleucine. Specifically, it is responsible for the fifth step in this process, in which 2-methyl-3-hydroxybutyryl-CoA is converted into 2-methylacetoacetyl-CoA. Through a similar method, the HSD10 enzyme processes a group of fats called branched-chain fatty acids.

This enzyme is also necessary for several chemical reactions involving female sex hormones (estrogens) and male sex hormones (androgens). HSD10 inactivates a potent form of estrogen called 17β-estradiol by converting it to a weaker form called estrone. This enzyme also generates a potent androgen called dihydrotestosterone from a weak androgen called 3α-androstanediol. The HSD10 enzyme is essential for maintaining appropriate levels of male and female sex hormones.

The HSD10 enzyme is needed for certain chemical reactions involving neurosteroids, which are substances that regulate the activity of the nervous system. This enzyme inactivates two neurosteroids called allopregnanolone and allotetrahydrodeoxycorticosterone. These neurosteroids interact with receptors that prevent the brain from being overloaded with too many signals. By regulating the activity of these neurosteroids, the HSD10 enzyme helps maintain normal brain function.

Does the HSD17B10 gene share characteristics with other genes?

The HSD17B10 gene belongs to a family of genes called SDR (short chain dehydrogenase/reductase superfamily).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the HSD17B10 gene related to health conditions?

17β-hydroxysteroid dehydrogenase type 10 deficiency - caused by mutations in the HSD17B10 gene

At least six mutations in the HSD17B10 gene have been found to cause 17β-hydroxysteroid dehydrogenase type 10 (HSD10) deficiency. These mutations change single amino acids in HSD10, which reduces or eliminates the activity of the enzyme. One mutation, which has been found in multiple unrelated individuals, replaces the amino acid arginine with the amino acid cysteine at position 130 in the enzyme (written as Arg130Cys or R130C). This mutation results in a nonfunctional enzyme that is quickly broken down by the cell. It remains unclear how a shortage (deficiency) of the HSD10 enzyme leads to the signs and symptoms of this disorder. Some researchers suspect that the neurological problems associated with HSD10 deficiency are caused by abnormal neurosteroid activity. Other features of the disorder may be related to the inability to process isoleucine and certain fats.

other disorders - caused by mutations in the HSD17B10 gene

One specific mutation in the HSD17B10 gene causes a form of X-linked intellectual disability called MRXS10. This disorder is characterized by intellectual disability, uncontrollable movements of the limbs (choreoathetosis), and abnormal behavior. The mutation replaces the DNA building block (nucleotide) cysteine with the nucleotide adenine at position 605 in the HSD17B10 gene (written as 605C>A). Although this mutation does not change the sequence of amino acids that makes up the HSD10 enzyme, it can disrupt how information in the gene is spliced together to make a blueprint for producing the enzyme. As a result, there is reduced production of the HSD10 enzyme. It remains unclear how the shortage of HSD10 results in the signs and symptoms of MRXS10.

At least 22 individuals with intellectual disability have been found to have small duplications of genetic material that include HSD17B10 and various other genes on the X chromosome. The extra copy of the HSD17B10 gene leads to increased production of the HSD10 enzyme, which likely affects neurosteroid regulation. Extra copies of other genes in this region of the X chromosome may also play a role in intellectual disability.

Where is the HSD17B10 gene located?

Cytogenetic Location: Xp11.2

Molecular Location on the X chromosome: base pairs 53,431,257 to 53,434,375

The HSD17B10 gene is located on the short (p) arm of the X chromosome at position 11.2.

The HSD17B10 gene is located on the short (p) arm of the X chromosome at position 11.2.

More precisely, the HSD17B10 gene is located from base pair 53,431,257 to base pair 53,434,375 on the X chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about HSD17B10?

You and your healthcare professional may find the following resources about HSD17B10 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the HSD17B10 gene or gene products?

  • ABAD
  • amyloid-beta peptide binding alcohol dehydrogenase
  • 17β-HSD10
  • 17-beta-hydroxysteroid dehydrogenase type 10
  • CAMR
  • ERAB
  • HADH2
  • HCD2
  • HCD2_HUMAN
  • HSD10
  • 3-hydroxy-2-methylbutyryl-CoA dehydrogenase
  • 3-hydroxyacyl-CoA dehydrogenase II
  • hydroxysteroid (17-beta) dehydrogenase 10 isoform 1
  • hydroxysteroid (17-beta) dehydrogenase 10 isoform 2
  • 2-methyl-3-hydroxybutyryl-CoA dehydrogenase
  • MHBD
  • MRPP2
  • SCHAD
  • SDR5C1
  • short chain 3-hydroxyacyl-CoA dehydrogenase
  • short chain dehydrogenase/reductase family 5C, member 1
  • short chain type dehydrogenase/reductase XH98G2
  • type 10 17beta-hydroxysteroid dehydrogenase
  • type 10 17b-HSD

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding HSD17B10?

acids ; adenine ; amino acid ; amyloid ; androgens ; arginine ; cell ; chromosome ; CoA ; cysteine ; deficiency ; dehydrogenase ; dihydrotestosterone ; DNA ; endoplasmic reticulum ; enzyme ; fatty acids ; gene ; isoleucine ; mental retardation ; methyl ; mitochondria ; mutation ; nervous system ; neurological ; nucleotide ; peptide ; protein

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Froyen G, Corbett M, Vandewalle J, Jarvela I, Lawrence O, Meldrum C, Bauters M, Govaerts K, Vandeleur L, Van Esch H, Chelly J, Sanlaville D, van Bokhoven H, Ropers HH, Laumonnier F, Ranieri E, Schwartz CE, Abidi F, Tarpey PS, Futreal PA, Whibley A, Raymond FL, Stratton MR, Fryns JP, Scott R, Peippo M, Sipponen M, Partington M, Mowat D, Field M, Hackett A, Marynen P, Turner G, Gécz J. Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. Am J Hum Genet. 2008 Feb;82(2):432-43. doi: 10.1016/j.ajhg.2007.11.002. Epub 2008 Jan 24. (http://www.ncbi.nlm.nih.gov/pubmed/18252223?dopt=Abstract)
  • Korman SH. Inborn errors of isoleucine degradation: a review. Mol Genet Metab. 2006 Dec;89(4):289-99. Epub 2006 Sep 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16950638?dopt=Abstract)
  • Lenski C, Kooy RF, Reyniers E, Loessner D, Wanders RJ, Winnepenninckx B, Hellebrand H, Engert S, Schwartz CE, Meindl A, Ramser J. The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior. Am J Hum Genet. 2007 Feb;80(2):372-7. Epub 2006 Dec 28. (http://www.ncbi.nlm.nih.gov/pubmed/17236142?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3028)
  • Ofman R, Ruiter JP, Feenstra M, Duran M, Poll-The BT, Zschocke J, Ensenauer R, Lehnert W, Sass JO, Sperl W, Wanders RJ. 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene. Am J Hum Genet. 2003 May;72(5):1300-7. Epub 2003 Apr 14. (http://www.ncbi.nlm.nih.gov/pubmed/12696021?dopt=Abstract)
  • OMIM: 17-BETA-HYDROXYSTEROID DEHYDROGENASE X (http://omim.org/entry/300256)
  • Perez-Cerda C, García-Villoria J, Ofman R, Sala PR, Merinero B, Ramos J, García-Silva MT, Beseler B, Dalmau J, Wanders RJ, Ugarte M, Ribes A. 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease. Pediatr Res. 2005 Sep;58(3):488-91. Erratum in: Pediatr Res. 2006 Jan;59(1):162. Perez-Cerda, Celia [added]; Ribes, Antonia [added]. (http://www.ncbi.nlm.nih.gov/pubmed/16148061?dopt=Abstract)
  • Reyniers E, Van Bogaert P, Peeters N, Vits L, Pauly F, Fransen E, Van Regemorter N, Kooy RF. A new neurological syndrome with mental retardation, choreoathetosis, and abnormal behavior maps to chromosome Xp11. Am J Hum Genet. 1999 Nov;65(5):1406-12. (http://www.ncbi.nlm.nih.gov/pubmed/10521307?dopt=Abstract)
  • Yang SY, He XY, Miller D. HSD17B10: a gene involved in cognitive function through metabolism of isoleucine and neuroactive steroids. Mol Genet Metab. 2007 Sep-Oct;92(1-2):36-42. Epub 2007 Jul 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17618155?dopt=Abstract)
  • Yang SY, He XY, Olpin SE, Sutton VR, McMenamin J, Philipp M, Denman RB, Malik M. Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism. Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14820-4. doi: 10.1073/pnas.0902377106. Epub 2009 Aug 17. (http://www.ncbi.nlm.nih.gov/pubmed/19706438?dopt=Abstract)
  • Yang SY, He XY, Schulz H. 3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease. FEBS J. 2005 Oct;272(19):4874-83. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16176262?dopt=Abstract)
  • Yang SY, He XY, Schulz H. Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase. Trends Endocrinol Metab. 2005 May-Jun;16(4):167-75. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15860413?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2009
Published: April 17, 2014