HSD17B10 : hydroxysteroid 17-beta dehydrogenase 10

Description

The HSD17B10 (hydroxysteroid 17-beta dehydrogenase 10) is a protein-coding gene located on chromosome X.

The HSD17B10 gene provides instructions for making a protein called HSD10. This protein is located within mitochondria, the energy-producing centers inside cells, where it has several different functions.The HSD10 protein is important for the production (synthesis) of proteins in mitochondria. (While most protein synthesis occurs in the fluid surrounding the nucleus, called the cytoplasm, a few proteins are synthesized in the mitochondria.) During protein synthesis, whether in the cytoplasm or in mitochondria, molecules called transfer RNAs (tRNAs) help assemble protein building blocks (amino acids) into the chains that form proteins. The HSD10 protein is involved in making functional mitochondrial tRNA. It forms a complex with an enzyme called TRMT10C to modify tRNAs so that they are more stable and can function properly. In addition, the complex interacts with another enzyme called PRORP to perform an enzymatic function called mitochondrial RNase P (mtRNase P) that cuts precursor RNA molecules, which is an essential step to generating tRNA molecules. Normal mitochondrial protein production, which requires tRNAs, is essential for the formation of the protein complexes that convert the energy from food into a form cells can use.The HSD10 protein also plays an important role in processing several substances in the body. It helps break down the 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 mechanism, the HSD10 protein also processes a group of fats called branched-chain fatty acids.The HSD10 protein is also thought to be involved in chemical reactions involving female sex hormones (estrogens) and male sex hormones (androgens). HSD10 turns off (inactivates) a potent form of estrogen called 17β-estradiol by converting it to a weaker form called estrone. HSD10 also generates a potent androgen called dihydrotestosterone from a weak androgen called 3α-androstanediol. These reactions are critical for maintaining appropriate levels of male and female sex hormones.The HSD10 protein also plays a role in certain chemical reactions involving neurosteroids, which are substances that regulate the activity of the nervous system. This protein 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 protein may help maintain normal brain function. However, other proteins in the body can also carry out these reactions, and the importance of HSD10 in these functions is unclear.

The HSD17B10 gene encodes a mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism. It functions as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid beta-oxidation, catalyzing the reversible conversion of (S)-3-hydroxyacyl-CoA to 3-ketoacyl-CoA during the third step of the beta-oxidation cycle. It preferentially accepts straight medium- and short-chain acyl-CoA substrates, showing highest efficiency for (3S)-hydroxybutanoyl-CoA. As 3-hydroxy-2-methylbutyryl-CoA dehydrogenase in the branched-chain amino acid catabolic pathway, it oxidizes 3-hydroxy-2-methylbutanoyl-CoA into 2-methyl-3-oxobutanoyl-CoA, a step in isoleucine degradation. It also displays hydroxysteroid dehydrogenase activity towards steroid hormones and bile acids, catalyzing the oxidation of 3alpha-, 17beta-, 20beta- and 21-hydroxysteroids, as well as 7alpha- and 7beta-hydroxy bile acids. It oxidizes allopregnanolone/brexanolone at the 3alpha-hydroxyl group, a process critical for the activation of gamma-aminobutyric acid receptors (GABAARs) chloride channel. The protein exhibits phospholipase C-like activity toward cardiolipin and its oxidized species. It likely oxidizes the 2'-hydroxyl in the head group of cardiolipin to form a ketone intermediate, which undergoes nucleophilic attack by water and fragments into diacylglycerol, dihydroxyacetone and orthophosphate. It has higher affinity for cardiolipin with oxidized fatty acids and may degrade these species during oxidative stress response to protect cells from apoptosis. By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD). HSD17B10 is essential for structural and functional integrity of mitochondria.

HSD17B10 is also known as 17b-HSD10, ABAD, CAMR, DUPXp11.22, ERAB, HADH2, HCD2, HSD10MD, MHBD, MRPP2, MRX17, MRX31, MRXS10, SCHAD, SDR5C1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing