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Protein HSD17B10 PDB 1so8.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases HSD17B10, 17b-HSD10, ABAD, CAMR, DUPXp11.22, ERAB, HADH2, HCD2, MHBD, MRPP2, MRX17, MRX31, MRXS10, SCHAD, SDR5C1, hydroxysteroid (17-beta) dehydrogenase 10, hydroxysteroid 17-beta dehydrogenase 10
External IDs MGI: 1333871 HomoloGene: 68403 GeneCards: HSD17B10
EC number
RNA expression pattern
PBB GE HSD17B10 202282 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr X: 53.43 – 53.43 Mb Chr X: 152 – 152 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

17-β-Hydroxysteroid dehydrogenase X (HSD10) also known as 3-hydroxyacyl-CoA dehydrogenase type-2 is a mitochondrial enzyme that in humans is encoded by the HSD17B10 (hydroxysteroid (17β) dehydrogenase 10) gene.[3][4][5][6][7] Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined.[8] Human HSD10 cDNA was cloned from brain (NM_004493), and the resulting protein, a homotetramer, was first characterized as a short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD).[9] Active sites of this enzyme can accommodate different substrates; 17β-HSD10 is involved in the oxidation of isoleucine, branched-chain fatty acids, and xenobiotics as well as the metabolism of sex hormones and neuroactive steroids.[10][11]


17beta-hydroxysteroid dehydrogenase 10 is a member of the short-chain dehydrogenase/reductase superfamily.[12] This homotetrameric mitochondrial multifunctional enzyme catalyzes the oxidation of neuroactive steroids and the degradation of isoleucine.[13] This enzyme is capable of binding to other peptides, such as estrogen receptor α, amyloid-β, and tRNA methyltransferase 10C. Missense mutations of the HSD17B10 gene result in 17β-HSD10 deficiency, an infantile neurodegeneration characterized by progressive psychomotor regression and alteration of mitochondria morphology. 17β-HSD10 exhibits only a negligible alcohol dehydrogenase activity, and is not localized in the endoplasmic reticulum or plasma membrane. Its alternate name – binding alcohol dehydrogenase (ABAD) – is a misnomer predicated on the mistaken belief that this enzyme is an alcohol dehydrogenase.[11]



Human HSD17B10 gene has 6 exons resides on the X chromosome at p11.22.[8]


The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids, and is a subunit of mitochondrial ribonuclease P, which is involved in tRNA maturation.[8] The molecular weight of 17β-HSD10 that is composed of four identical subunits is 108 kDa; each subunit consists of 261 amino acid residues.[14] Although the endoplasmic reticulum (ER)-associated amyloid-β peptide binding protein (ERAB) was reported to be associated with the ER and to consist of 262 residues with a molecular weight of 27 kDa,[15] ERAB is actually identical to 17β-HSD10 that is localized in mitochondria but not ER.[5]

Clinical significance[edit]

Abnormal expression, as well as mutations of the HSD17B10 gene leads to impairment of the structure, function, and dynamics of mitochondria. This may underlie the pathogenesis of the synaptic and neuronal deficiency exhibited in 17β-HSD10 related diseases, including 17β-HSD10 deficiency and Alzheimer's disease (AD).[8] Missense and silent mutations in the gene are the cause of hydroxysteroid (17β) dehydrogenase X (HSD10) deficiency, formerly MHBD deficiency, and X-linked mental retardation, choreoathetosis, and abnormal behavior (MRXS10), respectively.[13][16][17] Restoration of steroid homeostasis could be achieved by the supplementation of neuroactive steroids with a proper dosing and treatment regimen or by the adjustment of 17β-HSD10 activity to protect neurons.[11] The discovery of this enzyme's true function has opened a new therapeutic avenue for treating AD.


HSD17B10 has been shown to interact with Amyloid precursor protein.[10]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Marques AT, Antunes A, Fernandes PA, Ramos MJ (Sep 2006). "Comparative evolutionary genomics of the HADH2 gene encoding Abeta-binding alcohol dehydrogenase/17beta-hydroxysteroid dehydrogenase type 10 (ABAD/HSD10)". BMC Genomics. 7: 202. doi:10.1186/1471-2164-7-202. PMC 1559703Freely accessible. PMID 16899120. 
  4. ^ Yang SY, He XY, Miller D (Aug 2011). "Hydroxysteroid (17β) dehydrogenase X in human health and disease". Molecular and Cellular Endocrinology. 343 (1-2): 1–6. doi:10.1016/j.mce.2011.06.011. PMID 21708223. 
  5. ^ a b He XY, Merz G, Mehta P, Schulz H, Yang SY (May 1999). "Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase". The Journal of Biological Chemistry. 274 (21): 15014–9. doi:10.1074/jbc.274.21.15014. PMID 10329704. 
  6. ^ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Mar 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1-3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744Freely accessible. PMID 19027726. 
  7. ^ Holzmann J, Frank P, Löffler E, Bennett KL, Gerner C, Rossmanith W (Oct 2008). "RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme". Cell. 135 (3): 462–74. doi:10.1016/j.cell.2008.09.013. PMID 18984158. 
  8. ^ a b c d "Entrez Gene: HSD17B10 hydroxysteroid (17-beta) dehydrogenase 10". 
  9. ^ He XY, Yang YZ, Schulz H, Yang SY (Jan 2000). "Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase". The Biochemical Journal. 345 (1): 139–43. doi:10.1042/bj3450139. PMC 1220740Freely accessible. PMID 10600649. 
  10. ^ a b Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama M, Ogawa S, Roher A, Stern D (Oct 1997). "An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease". Nature. 389 (6652): 689–95. doi:10.1038/39522. PMID 9338779. 
  11. ^ a b c Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (Sep 2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in neurodegenerative disorders". The Journal of Steroid Biochemistry and Molecular Biology. 143: 460–72. doi:10.1016/j.jsbmb.2014.07.001. PMID 25007702. 
  12. ^ Yang SY, He XY, Schulz H (2005). "Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase". Trends in Endocrinology and Metabolism. 16 (4): 167–75. doi:10.1016/j.tem.2005.03.006. PMID 15860413. 
  13. ^ a b Yang SY, He XY, Olpin SE, Sutton VR, McMenamin J, Philipp M, Denman RB, Malik M (Sep 2009). "Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism". Proceedings of the National Academy of Sciences of the United States of America. 106 (35): 14820–4. doi:10.1073/pnas.0902377106. PMC 2728107Freely accessible. PMID 19706438. 
  14. ^ He XY, Schulz H, Yang SY (Apr 1998). "A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease". The Journal of Biological Chemistry. 273 (17): 10741–6. doi:10.1074/jbc.273.17.10741. PMID 9553139. 
  15. ^ Beyreuther K, Masters CL (Oct 1997). "Alzheimer's disease. The ins and outs of amyloid-beta". Nature. 389 (6652): 677–8. doi:10.1038/39479. PMID 9338775. 
  16. ^ Seaver LH, He XY, Abe K, Cowan T, Enns GM, Sweetman L, Philipp M, Lee S, Malik M, Yang SY (November 2011). "A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, choreoathetosis and learning disability". PLOS ONE. 6 (11): e27348. doi:10.1371/journal.pone.0027348. PMC 3222643Freely accessible. PMID 22132097. 
  17. ^ Lenski C, Kooy RF, Reyniers E, Loessner D, Wanders RJ, Winnepenninckx B, Hellebrand H, Engert S, Schwartz CE, Meindl A, Ramser J (Feb 2007). "The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior". American Journal of Human Genetics. 80 (2): 372–7. doi:10.1086/511527. PMC 1785340Freely accessible. PMID 17236142. 

Further reading[edit]