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HSD3B7
hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7
The *HSD3B7* gene provides instructions for an enzyme called 3 beta-hydroxysteroid dehydrogenase type 7 (3β-HSD7), which plays a critical role in the synthesis of bile acids within the liver. The *HSD3B7* gene is essential for producing the 3β-HSD7 enzyme, a key component in the metabolic pathway that converts cholesterol into bile acids.
HSD3B7 is located on the short (p) arm of chromosome 16, at band 16p11.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The *HSD3B7* gene, also known as hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7, is vital for proper liver function. It encodes an enzyme that performs a specific step in the complex process of bile acid synthesis. Bile acids are essential for digestion and nutrient absorption, particularly fats and fat-soluble vitamins.
Dysfunction of the enzyme produced by *HSD3B7* can disrupt this synthesis, leading to various health issues related to impaired bile flow and metabolism. Understanding this gene's role is important for diagnosing and managing associated conditions.
What the gene does
The *HSD3B7* gene directs the production of an enzyme called 3 beta-hydroxysteroid dehydrogenase type 7 (3β-HSD7). This enzyme is located within the liver cells, specifically embedded in the membrane of the endoplasmic reticulum, which is a cellular structure involved in protein processing and transport.
Its primary function is to catalyse a crucial step in the conversion of cholesterol into bile acids. Specifically, the 3β-HSD7 enzyme is responsible for transforming 7α-hydroxycholesterol into 7α-hydroxy-4-cholesten-3-one. This reaction is the second stage in the multi-step pathway of bile acid synthesis, which ultimately leads to the production of bile, a digestive fluid vital for emulsifying fats and absorbing fat-soluble vitamins.
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Chromosome location
The *HSD3B7* gene is situated on chromosome 16, specifically at position 16p11.2. This location refers to the short (p) arm of chromosome 16, within region 1, band 1, sub-band 2. The precise chromosomal address helps in mapping the gene and understanding its genomic context.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the *HSD3B7* gene can alter the normal function of the 3β-HSD7 enzyme. These genetic changes can range from small deletions or insertions of DNA building blocks to single base-pair substitutions. Such alterations can impair the enzyme's ability to participate effectively in bile acid synthesis, leading to a deficiency in functional bile acids.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.294dup | p.Lys99fs | Pathogenic | ★★☆☆ | not provided |
c.439G>A | p.Glu147Lys | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital bile acid synthesis defect 1 |
c.45_46del | p.Gly17fs | Pathogenic | ★★☆☆ | Congenital bile acid synthesis defect |
c.499G>T | p.Glu167Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital bile acid synthesis defect 1 |
c.79C>T | p.Arg27Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.890del | p.Phe297fs | Pathogenic | ★★☆☆ | not provided |
c.16C>T | p.Gln6Ter | Pathogenic | ★☆☆☆ | Congenital bile acid synthesis defect 1 |
c.323-1G>C | - | Pathogenic | ★☆☆☆ | not provided |
c.503G>A | p.Trp168Ter | Pathogenic | ★☆☆☆ | not provided |
c.618C>G | p.Tyr206Ter | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the *HSD3B7* gene are primarily associated with Primary Bile Acid Synthesis Defect (3β-HSD). This is an inherited metabolic disorder characterised by the body's inability to produce sufficient or proper bile acids, which can lead to a build-up of toxic bile acid precursors and cholestasis, a condition where bile flow from the liver is impaired.
- Primary bile acid synthesis defect (3β-HSD) Dedicated page coming soon
UK clinical status
The *HSD3B7* gene is part of several Green RAG (Red Amber Green) rated panels within the NHS Genomic Medicine Service's PanelApp, indicating its strong association with specific conditions. It is included in panels for Cholestasis, DDG2P (Developmental Disorders Gene to Phenotype), Likely inborn error of metabolism, Neonatal cholestasis, and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the *HSD3B7* gene?
The *HSD3B7* gene provides instructions for the 3β-HSD7 enzyme, which is crucial for synthesising bile acids from cholesterol in the liver. Bile acids are vital for fat digestion and absorption.
What happens if the *HSD3B7* gene doesn't work correctly?
If the *HSD3B7* gene is not functioning correctly, it can lead to a deficiency in bile acid production. This can result in conditions like Primary Bile Acid Synthesis Defect, characterised by impaired bile flow and digestive issues.
How is *HSD3B7* related to liver health?
*HSD3B7* is directly linked to liver health because the enzyme it produces, 3β-HSD7, is active in liver cells and essential for the proper synthesis of bile acids, which are crucial for normal liver function and digestion.
References
- Gioiello A, Cerra B, Zhang W. Synthesis of atypical bile acids for use as investigative tools for the genetic defect of 3β-hydroxy-Δ(5)-C27-steroid oxidoreductase deficiency. The Journal of steroid biochemistry and molecular biology. 2014. PMID: 24954360
- Subramaniam P, Clayton PT, Portmann BC. Variable clinical spectrum of the most common inborn error of bile acid metabolism--3beta-hydroxy-Delta 5-C27-steroid dehydrogenase deficiency. Journal of pediatric gastroenterology and nutrition. 2010. PMID: 19915491
- Cheng JB, Jacquemin E, Gerhardt M. Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease. The Journal of clinical endocrinology and metabolism. 2003. PMID: 12679481