HSD17B13

Official Full Name

hydroxysteroid 17-beta dehydrogenase 13

Organism

Homo sapiens

GeneID

345275

Background

Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor and steroid dehydrogenase activity. Acts upstream of or within positive regulation of lipid biosynthetic process. Located in lipid droplet. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

FLDP; SCDR9; NIIL497; SDR16C3; HMFN0376;

Protein Sequence

MNIILEILLLLITIIYSYLESLVKFFIPQRRKSVAGEIVLITGAGHGIGRQTTYEFAKRQSILVLWDINKRGVEETAAECRKLGVTAHAYVVDCSNREEIYRSLNQVKKEVGDVTIVVNNAGTVYPADLLSTKDEEITKTFEVNILGHFWITKALLPSMMERNHGHIVTVASVCGHEGIPYLIPYCSSKFAAVGFHRGLTSELQALGKTGIKTSCLCPVFVNTGFTKNPSTRLWPVLETDEVVRSLIDGILTNKKMIFVPSYINIFLRLQKFLPERASAILNRMQNIQFEAVVGHKIKMK

Open

Disease

Non-alcoholic fatty liver disease

Approved Drug

Clinical Trial Drug

1 +

Discontinued Drug

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

A member of the HSD17B family, hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) is an enzyme helping to metabolize liver lipids. Liu S and colleagues discovered this liver-specific lipid droplet-associated protein in 2007. It helps to regulate the intricate processes of lipid synthesis and breakdown. Especially in the liver, HSD17B13 is most pronounced. Other organs, including the ovaries, bone marrow, and kidneys, also contain it in lesser concentrations. HSD17B13 is part of a bigger family function together with its paralog HSD17B11, which shares much with HSD17B13. Chromosome 4q22.1 carries the HSD17B13 gene. With molecular weights varying from 22 to 33 kDa, it generates several types of proteins utilizing alternative splicing.

The protein can oxidoreductase, meaning it can operate on fatty substrates using either NAD or NADP. Its significance for lipid particle structure and breakdown is high. HSD17B13's most crucial function is converting retinol to retinal. For the liver to function and for maintaining cellular homeostasis, this alteration is quite significant. Genetic variations in HSD17B13, such as the splice variant rs72613567:TA, have been connected to a protective impact against fatty liver-related inflammation and a rise in liver enzymes, which indicates how crucial it is for liver health.

Mechanisms and Impact on Metabolic Diseases

Non-alcoholic fatty liver disease (NAFLD) and other metabolic problems can be partly controlled by HSD17B13. Through its part in lipid metabolism, it helps slow the development of disease. This is mostly made easier by the way it interacts with control factors such as LXR-α, which changes gene translation in lipid pathways. Some genetic variations in HSD17B13 can cause big changes in enzyme activity, which can make it harder for the liver to handle fats properly.

Because it is involved in liver diseases, HSD17B13 is a key part of understanding non-alcoholic steatohepatitis (NASH). Its expression controls the movement of lipid droplets in NASH, keeping the building up and breaking down of lipid stores in balance. Controlling retinoid pathways through HSD17B13 also affects the activity of liver stellate cells and the immune system, both of which are important in the fibrotic process.

The figure illustrates the proposed mechanism by which HSD17B13 modulates disease progression in NAFLD, highlighting its role in retinol metabolism, lipid droplet regulation, and the impact of genetic polymorphisms on liver disease progression. Figure 1. Proposed role of HSD17B13 in modulating disease progression in NAFLD. (Amangurbanova M, et al., 2023)

Therapeutic Strategies Targeting HSD17B13

Targeting HSD17B13 using RNA interference (RNAi) has shown promise. RNAi treatments reduce protein expression and silence particular genes using small interfering RNA (siRNA), a kind of molecule. ALN-HSD, developed by Alnylam Pharmaceuticals, demonstrates this kind of treatment. Now in Phase I clinical studies, it is promising in reducing liver enzyme indicators and HSD17B13 mRNA levels.

Another GalNAc-conjugated siRNA in Phase I studies is Arrowhead Pharmaceuticals' ARO-HSD. Its mechanism is selective targeting of HSD17B13 mRNA in liver cells. The liver's mRNA and protein levels were shown to be quite low.

Small molecule inhibitors provide another means of targeting proteins within cells, including HSD17B13, for therapy. Inipharm's INI-822 is being investigated in a Phase I trial for NASH in this manner. Though its development has been hampered by bad pharmacokinetic characteristics, Boehringer Ingelheim's investigational drug BI-3231 shows good efficacy and selectivity.

These new drugs point strongly to HSD17B13 as a possible treatment for liver conditions. They provide fresh avenues for physicians to assist patients and reduce liver damage. New research and development might open up new options for treating metabolic liver illnesses, which would help to manage circumstances like NASH.

References:

Demirtas CO, Yilmaz Y. Decoding 17-Beta-hydroxysteroid Dehydrogenase 13: A Multifaceted Perspective on Its Role in Hepatic Steatosis and Associated Disorders. J Clin Transl Hepatol. 2024;12(10):857-864.
Su W, Mao Z, Liu Y, et al. Role of HSD17B13 in the liver physiology and pathophysiology. Mol Cell Endocrinol. 2019;489:119-125.
Zhang HB, Su W, Xu H, et al. HSD17B13: A Potential Therapeutic Target for NAFLD. Front Mol Biosci. 2022 Jan 7;8:824776.
Amangurbanova M, Huang DQ, Loomba R. Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD. Aliment Pharmacol Ther. 2023;57(1):37-51.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry