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CYP7B1
cytochrome P450 family 7 subfamily B member 1
The CYP7B1 gene provides instructions for an enzyme crucial in both bile acid synthesis within the liver and neurosteroid formation in the brain. CYP7B1 is a member of the cytochrome P450 gene family, responsible for producing the oxysterol 7-alpha-hydroxylase enzyme.
CYP7B1 is located on the long (q) arm of chromosome 8, at band 8q12.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The CYP7B1 gene, also known as cytochrome P450 family 7 subfamily B member 1, plays a central role in several metabolic processes. It codes for the enzyme oxysterol 7-alpha-hydroxylase, which is primarily active in the liver and the brain. In the liver, this enzyme aids in breaking down cholesterol to produce bile acids, which are vital for digesting fats. Within the brain, it participates in synthesising neurosteroids, hormones that enhance nerve cell excitability. Investigations into CYP7B1 variants are important for understanding conditions related to cholesterol metabolism and neurological function.
What the gene does
The CYP7B1 gene encodes the enzyme oxysterol 7-alpha-hydroxylase, which belongs to the cytochrome P450 family. Enzymes from this family are generally involved in numerous biochemical reactions, including the creation and degradation of molecules within cells. The oxysterol 7-alpha-hydroxylase enzyme has distinct functions in different tissues. In the liver, it contributes to the classic pathway for bile acid synthesis, acting on cholesterol derivatives to generate primary bile acids that facilitate fat digestion [PMID:10072044]. Within the brain, the enzyme transforms specific forms of cholesterol into neurosteroids. These neurosteroids are essential for increasing the excitability of nerve cells, thereby impacting neuronal communication [PMID:10072044]. Consequently, CYP7B1 helps maintain appropriate cholesterol levels in the brain and regulates the impact of neurosteroids on brain function.
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Chromosome location
The CYP7B1 gene is located on chromosome 8, specifically at position 8q12.3. This designation refers to its precise site on the long arm of chromosome 8. The gene contains several exons, which are segments of DNA that are transcribed and translated to form the functional oxysterol 7-alpha-hydroxylase enzyme.
Protein structure
The CYP7B1 gene produces a protein composed of 506 amino acids. This protein functions as the oxysterol 7-alpha-hydroxylase enzyme.
Key variants
Genetic changes, or variants, within the CYP7B1 gene can alter the function of the oxysterol 7-alpha-hydroxylase enzyme. These variants can range from single nucleotide alterations to larger deletions or insertions, potentially resulting in reduced enzyme activity or a complete loss of function. The specific effect of a variant often depends on its location within the gene and how it influences the protein's structure and stability.
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.1081C>T | p.Arg361Ter | Pathogenic/Likely pathogenic | ★★☆☆ | CYP7B1-related disorder |
c.1150del | p.Asp384fs | Pathogenic/Likely pathogenic | ★★☆☆ | Spastic paraplegia |
c.1233+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Spastic paraplegia |
c.1254del | p.Phe418fs | Pathogenic/Likely pathogenic | ★★☆☆ | CHD7-related CHARGE syndrome |
c.173dup | p.Val59fs | Pathogenic/Likely pathogenic | ★★☆☆ | CYP7B1-related disorder |
c.260-1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Spastic paraplegia |
c.314dup | p.Asn105fs | Pathogenic/Likely pathogenic | ★★☆☆ | Spastic paraplegia |
c.392dup | p.Asn131fs | Pathogenic | ★★☆☆ | Spastic paraplegia |
c.631_635del | p.Glu211fs | Pathogenic | ★★☆☆ | Spastic paraplegia |
c.650T>A | p.Leu217Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary spastic paraplegia 5A |
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
Pathogenic variants in the CYP7B1 gene are primarily associated with inherited conditions affecting neurological function and metabolism. Spastic paraplegia type 5A is a notable condition linked to CYP7B1 variants, characterised by progressive muscle stiffness and weakness, particularly in the lower limbs [PMID:24619330]. These variants typically diminish the activity of the oxysterol 7-alpha-hydroxylase enzyme, impairing its crucial roles in cholesterol metabolism and neurosteroid production.
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UK clinical status
In the UK, the CYP7B1 gene is listed on several NHS England Genomic Medicine Service clinical panels, reflecting its recognised clinical importance. These panels include Hereditary spastic paraplegia, Hereditary spastic paraplegia, adult onset, and Hereditary spastic paraplegia, childhood onset. It is also included in panels for Cholestasis, Neonatal cholestasis, Likely inborn error of metabolism, Undiagnosed metabolic disorders, and White matter disorders and cerebral calcification - childhood onset, all of which are green-rated.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the CYP7B1 gene?
The CYP7B1 gene provides instructions for making the oxysterol 7-alpha-hydroxylase enzyme. This enzyme plays a crucial role in converting cholesterol into bile acids in the liver and into neurosteroids in the brain, which are important for nerve cell signalling.
What health conditions are associated with changes in the CYP7B1 gene?
Pathogenic variants in the CYP7B1 gene are primarily linked to Spastic paraplegia type 5A, a condition characterised by muscle stiffness and weakness in the lower limbs. These variants generally lead to reduced activity of the oxysterol 7-alpha-hydroxylase enzyme.
Where is the CYP7B1 gene primarily active in the body?
The CYP7B1 gene is primarily active in the liver and the brain. In the liver, it helps process cholesterol into bile acids, and in the brain, it contributes to the production of neurosteroids which impact nerve cell function.
References
- Arnoldi A, Crimella C, Tenderini E. Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations. Clinical genetics. 2012. PMID: 21214876
- Goizet C, Boukhris A, Durr A. CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain : a journal of neurology. 2009. PMID: 19439420
- Tsaousidou MK, Ouahchi K, Warner TT. Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. American journal of human genetics. 2008. PMID: 18252231