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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CYP7A1
cytochrome P450 family 7 subfamily A member 1
Chromosome 8 · 8q12.1
NCBI Gene: 1581Ensembl: ENSG00000167910.4HGNC: HGNC:2651UniProt: P22680
132PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
bile acid biosynthetic processcholesterol 7-alpha-monooxygenase activityregulation of bile acid biosynthetic processcellular response to glucose stimuluscholelithiasisCholecystitismetabolic diseasehypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency
✦AI Summary

CYP7A1 (cytochrome P450 family 7 subfamily A member 1) is a liver-specific microsomal enzyme that catalyzes the first and rate-limiting step in bile acid synthesis by hydroxylating cholesterol at the 7-alpha position to form 7-alpha-hydroxycholesterol 1. As a cytochrome P450 monooxygenase, CYP7A1 uses molecular oxygen to insert one atom into cholesterol substrates while reducing the second into water, with electrons supplied by NADPH via cytochrome P450 reductase 2. Beyond classical bile acid synthesis, CYP7A1 metabolizes oxysterols including 4-beta-hydroxycholesterol and 24-hydroxycholesterol, and oxidizes sterol precursors like 7-dehydrocholesterol 3. CYP7A1 expression is tightly regulated through a gut-liver axis: the intestinal bile acid sensor FXR stimulates FGF15 secretion, which signals to hepatic FGFR4 to suppress CYP7A1 via SHP-mediated mechanisms 1. Additionally, PCSK9 inhibition activates CYP7A1 through PPARα-mediated transcription, promoting cholesterol-to-bile acid conversion 4. CYP7A1 dysregulation contributes to cholesterol gallstone formation and NAFLD pathogenesis, with reduced bile acid synthesis linked to improved lipid metabolism and selective suppression of saturated fatty acid absorption 5. Multiple transcription factors including HNF1α, LXRβ, and MEF2A regulate CYP7A1 expression, with epigenetic modifications influencing hepatic cholesterol homeostasis 67.

Sources cited
1
CYP7A1 catalyzes the first and rate-limiting step in bile acid synthesis and is repressed by FGF15-FGFR4-SHP gut-liver signaling
PMID: 16213224
2
CYP7A1 is a liver-specific microsomal monooxygenase that converts cholesterol to 7-alpha-hydroxycholesterol
PMID: 16434543
3
CYP7A1 metabolizes oxysterols and uses molecular oxygen insertion mechanism with NADPH-dependent electron transfer
PMID: 12077124
4
PCSK9 inhibition activates CYP7A1 through PPARα-mediated transcription to facilitate cholesterol conversion to bile acids and prevent cholesterol gallstones
PMID: 38191052
5
Reduced bile acid synthesis via CYP7A1 disruption prevents obesity and selectively reduces saturated fatty acid absorption
PMID: 41386220
6
HNF1α and LXRβ regulate CYP7A1 transcription in gallstone disease pathogenesis
PMID: 36836631
7
MEF2A transcription factor directly modulates CYP7A1 expression through epigenetic DNA methylation mechanisms
PMID: 39695937
Disease Associationsⓘ20
cholelithiasisOpen Targets
0.48Moderate
CholecystitisOpen Targets
0.41Moderate
metabolic diseaseOpen Targets
0.38Weak
hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiencyOpen Targets
0.37Weak
hyperlipidemiaOpen Targets
0.37Weak
familial hyperlipidemiaOpen Targets
0.34Weak
HypercholesterolemiaOpen Targets
0.33Weak
physical activityOpen Targets
0.23Weak
gallstonesOpen Targets
0.22Weak
gallbladder diseaseOpen Targets
0.17Weak
Intrahepatic cholestasis of pregnancyOpen Targets
0.14Weak
liver diseaseOpen Targets
0.13Weak
cholestasis, intrahepatic, of pregnancy 3Open Targets
0.09Suggestive
neoplasmOpen Targets
0.08Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
steatosisOpen Targets
0.05Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.05Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.04Suggestive
intestinal neoplasmOpen Targets
0.04Suggestive
Pathogenic Variants1
NM_000780.4(CYP7A1):c.959del (p.Glu320fs)Pathogenic
not provided
★☆☆☆2017→ Residue 320
View on ClinVar ↗
Related Genes
NR5A2Protein interaction100%LSSProtein interaction100%NR1I3Protein interaction97%CH25HProtein interaction97%STSProtein interaction95%CELProtein interaction95%
Tissue Expression6 tissues
Liver
100%
Ovary
2%
Lung
2%
Brain
1%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
CYP7A1NR5A2LSSNR1I3CH25HSTSCEL
PROTEIN STRUCTURE
Preparing viewer…
PDB3V8D · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.82LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.59 [0.43–0.82]
RankingsWhere CYP7A1 stands among ~20K protein-coding genes
  • #3,518of 20,598
    Most Researched132 · top quartile
  • #4,802of 5,498
    Most Pathogenic Variants1
  • #6,949of 17,882
    Most Constrained (LOEUF)0.82
Genes detectedCYP7A1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Inhibition of PCSK9 prevents and alleviates cholesterol gallstones through PPARα-mediated CYP7A1 activation.
PMID: 38191052
Metabolism · 2024
1.00
2
Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD.
PMID: 28774887
Gut · 2018
0.90
3
Bile acids regulate lipid metabolism through selective actions on fatty acid absorption.
PMID: 41386220
Cell Metab · 2026
0.80
4
Human CYP7A1 deficiency: progress and enigmas.
PMID: 12093884
J Clin Invest · 2002
0.70
5
FGF15 Activates Hippo Signaling to Suppress Bile Acid Metabolism and Liver Tumorigenesis.
PMID: 30745141
Dev Cell · 2019
0.60