CYP7A1

Summary

CYP7A1 (cytochrome P450 family 7 subfamily A member 1, HGNC:2651) is a protein-coding gene on chromosome 8q12.1, encoding Cytochrome P450 7A1 (P22680). A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols).

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway in the liver, which converts cholesterol to bile acids. This reaction is the rate limiting step and the major site of regulation of bile acid synthesis, which is the primary mechanism for the removal of cholesterol from the body. Polymorphisms in the promoter of this gene are associated with defects in bile acid synthesis.

Source: NCBI Gene 1581 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency (Supportive, GenCC)
• GWAS associations: 19
• Clinical variants (ClinVar): 251 total — 1 pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• MANE Select transcript: NM_000780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2651
Approved symbol	CYP7A1
Name	cytochrome P450 family 7 subfamily A member 1
Location	8q12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167910
Ensembl biotype	protein_coding
OMIM	118455
Entrez	1581

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000301645

RefSeq mRNA: 1 — MANE Select: NM_000780 NM_000780

CCDS: CCDS6171

Canonical transcript exons

ENST00000301645 — 6 exons

Exon	Start	End
ENSE00001118229	58492353	58492528
ENSE00001118230	58496604	58497190
ENSE00001118231	58500019	58500163
ENSE00001118232	58494506	58494636
ENSE00001118233	58490178	58491774
ENSE00001118234	58498229	58498469

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 73.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0766 / max 48.4563, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93191	0.0766	7

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	73.19	gold quality
liver	UBERON:0002107	73.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.38	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
quadriceps femoris	UBERON:0001377	49.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
vastus lateralis	UBERON:0001379	49.16	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
epithelial cell of pancreas	CL:0000083	48.02	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
thymus	UBERON:0002370	47.87	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.43
E-CURD-10	no	7.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHE40, BHLHE41, CEBPA, CUX1, DBP, FGF19, FOXA1, FOXA2, FOXM1, FOXN1, FOXO1, HDAC7, HLF, HNF1A, HNF4A, JUN, KLF9, NCOA1, NFIL3, NR0B2, NR1D1, NR1D2, NR1H2, NR1H3, NR1H4, NR1I2, NR1I3, NR2F2, NR5A2, PITX2, PPARA, PPARG, PPARGC1A, PROX1, RARA, RXRA, SIRT1, SMAD3, SP1, SREBF1

miRNA regulators (miRDB)

82 targeting CYP7A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-548M	99.70	68.87	1749

Literature-anchored findings (GeneRIF, showing 40)

• CYP7A1 regulates the pathway through which cholesterol is converted into bile acids. (PMID:11907135)
• regulation of CYP7A1 and CYP27A1 in human liver (PMID:12011083)
• Human CYP7A1 deficiency: progress and enigmas. Review. (PMID:12093884)
• New metabolic disorder presenting with hyperlipidemia caused by a homozygous deletion mutation in CYP7A1. (PMID:12093894)
• data suggest that the lack of an LXR element in the region from -56 to -49 of the human CYP7A1 promoter may account for some of the differences in response to diets between humans and rodents (PMID:12202481)
• characterization of the coordinated regulation of cholesterol metabolism in human liver; regulation of its mRNA in liver (PMID:12213890)
• Data reveal a fundamental difference in the regulation of CYP7A1 in rodent and human hepatocytes. (PMID:12554795)
• demonstrated that FGF-19, acting as an FXR-induced signaling molecule, represses expression of the CYP7A1 gene; this signaling cascade defines a novel mechanism for feedback repression of bile acid biosynthesis (PMID:12815072)
• bile acids suppress transcription of the gene (CYP7A1) encoding cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis (PMID:12865425)
• CYP7A1 is activated by PGC-1alpha (PMID:14522988)
• data indicate that thyroid hormone can repress the human cholesterol 7 alpha-hydroxylase(CYP7A1) gene in transgenic mice, but this effect is dependent on gender (PMID:14592954)
• dietary cholesterol regulates bile acid pool size, fecal bile acid excretion, and plasma cholesterol independently of Cyp7a1 activity (PMID:14762172)
• The liver receptor homolog-1 has emerged as an essential regulator for the expression of CYP7A1. (PMID:15205472)
• CYP7A1 polymorphism has a small but significant effect on the increase in plasma HDL cholesterol and plasma total cholesterol after an increased intake of dietary cholesterol and cafestol, respectively. (PMID:15333704)
• Present study indicates that a tight fit of cholesterol in the CYP7A1 active site is in part responsible for the high efficiency of cholesterol turnover by CYP7A1 in the liver. (PMID:15736936)
• This study has found that several kinase activators rapidly reduce the amount of bile acid produced by the human hepatoma cell line, HepG2, and that gpCYP7A1 from HepG2 cell extracts eluted in the phosphoprotein fraction of FeIII columns. (PMID:15752749)
• regulation by HNF-4alpha (PMID:15796896)
• common polymorphisms of the CYP7A1 gene do not contribute to variation in cholesterol 7alpha-hydroxylase activity, rates of bile acid synthesis and plasma LDL cholesterol concentration in humans (PMID:16115473)
• The findings add to evidence for the role of bile acids in colorectal carcinogenesis. The CC genotype of the CYP7A1 A-203C polymorphism probably renders lower activity of the enzyme synthesizing bile acids. (PMID:16630139)
• A constant genetic structure in CYP7A1 gene and its surrounding sequences was found that may lead to a better design for association studies of genetic variations in CYP7A1 gene with cholesterol and bile acid metabolism. (PMID:16709249)
• T(3) dose-dependently decreased total bile acid formation in parallel with decreased expression of CYP7A1 and CYP8B1 (PMID:16937432)
• TGFbeta1 represses CYP7A1 gene transcription in human hepatocytes by a mechanism involving Smad3-dependent inhibition of HNF4alpha and histone deacetylase remodeling of CYP7A1 chromatin. (PMID:17920062)
• the association of A-204C variation of CYP7A1 gene promoter polymorphism in gallbladder cancer patients, gallstone patients and healthy subjects (PMID:18178499)
• Liver receptor homolog 1 (LRH-1) is a key transcriptional factor required for the hepatic expression of CYP7A1. (PMID:18270374)
• CYP7A1 promoter polymorphism is not a valuable marker of gallstone disease susceptibility in a Polish population. (PMID:18307386)
• PGC-1alpha is an important co-activator for LRH-1 and that SHP targets the interaction between LRH-1 and PGC-1alpha to inhibit CYP7A1 expression. (PMID:18385139)
• The cholesterol 7 alpha-hydroxylase A-204C polymorphism was positively associated with the presence of atherosclerotic plaque and carotid and femoral intima-media thickness in health postmenopausal women (PMID:18665040)
• common variant A203C of the CYP7A1 gene markedly affects cholesterol 7-alpha-hydroxylase activity in patients with severe bile salt malabsorption (PMID:18728290)
• the effect of a common -203A>C polymorphism in the CYP7A1 promoter region on the activity of CYP7A1 (PMID:18728290)
• In the absence of changes in short heterodimer partner mRNA, CYP7A1 mRNA was strongly reduced in the liver of cholestatic patients in comparison with drained and control patients. (PMID:19185005)
• The study provides evidence that -278A>C polymorphism in the CYP7A1 gene can modify triglyceride concentrations in response to a reduced fat diet in a dyslipidemic male population. (PMID:19448895)
• Impaired regulation of FoxO1 may cause down-regulation of CYP7A1 gene expression and contribute to dyslipidemia in insulin resistance. (PMID:19463968)
• insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans (PMID:19537927)
• Data show that 12 SNPs from CETP, APOAI, ABCB1, CYP7A1, and HMGCR genes to be associated with baseline LDL-C and high-density lipoprotein cholesterol levels and increased risk of CAD. (PMID:19558216)
• Statistical analyses revealed that a common promoter SNP in CYP7A1 has a protective/gene dose-dependent effect on the risk of NMO. (PMID:19850125)
• study found glucose positively regulated hepatocyte CYP7A1 gene & bile acid synthesis; this glucose-mediated induction of CYP7A1 transcription may be mediated by both AMPK-dependent pathway & epigenetic regulation of CYP7A1 chromatin structure (PMID:19965590)
• mechanism for gallbladder cancer susceptibility by CYP7A1 haplotype appears to be independent of gallstone pathway and is believed to involve genotoxicity resulting from subnormal bile acid production (PMID:20005541)
• miR-122a and miR-422a may destabilize CYP7A1 mRNA to inhibit CYP7A1 expression. (PMID:20351063)
• The mRNA expression levels of sodium taurocholate cotransporting polypeptide, bile salt export pump, and hepatic cholesterol 7alpha-hydroxylase were significantly higher in the primary biliary cirrhosis patients than in the controls. (PMID:20857261)
• These results demonstrate that no association exists between apoB-100, apoE, and CYP7A1 polymorphisms and cholelithiasis in a Mexican population. (PMID:20872969)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp7a1	ENSDARG00000069018
mus_musculus	Cyp7a1	ENSMUSG00000028240
rattus_norvegicus	Cyp7a1	ENSRNOG00000009488

Paralogs (2): CYP39A1 (ENSG00000146233), CYP7B1 (ENSG00000172817)

Protein

Protein identifiers

Cytochrome P450 7A1 — P22680 (reviewed: P22680)

Alternative names: 24-hydroxycholesterol 7-alpha-hydroxylase, CYPVII, Cholesterol 7-alpha-hydroxylase, Cholesterol 7-alpha-monooxygenase

All UniProt accessions (1): P22680

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Functions as a critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis. Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol, a rate-limiting step in cholesterol catabolism and bile acid biosynthesis. 7-alpha hydroxylates several oxysterols, including 4beta-hydroxycholesterol and 24-hydroxycholesterol. Catalyzes the oxidation of the 7,8 double bond of 7-dehydrocholesterol and lathosterol with direct and predominant formation of the 7-keto derivatives.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Detected in liver.

Induction. Up-regulated by glucose and by cholestyramine. Down-regulated by chenodeoxycholic acid.

Pathway. Lipid metabolism; bile acid biosynthesis. Steroid metabolism; cholesterol degradation.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_000771* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002403	Cyt_P450_E_grp-IV	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR024204	Cyt_P450_CYP7A1-type	Family
IPR030681	Cholesterol_7a_monooxygenase	Family
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050529	CYP51A1-like	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.14.23 — cholesterol 7alpha-monooxygenase (BRENDA: 9 organisms, 25 substrates, 5 inhibitors, 8 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CHOLESTEROL	0.015–0.052	3
LATHOSTEROL	0.0018–0.0021	2
7-DEHYDROCHOLESTEROL	0.0011	1
O2	0.02	1
25-HYDROXYCHOLESTEROL	—	0
27-HYDROXYCHOLESTEROL	—	0
CHOLEST-4-EN-3-ONE	—	0

Catalyzed reactions (Rhea), 7 shown:

• (24R)-hydroxycholesterol + reduced [NADPH–hemoprotein reductase] + O2 = (24R)-7alpha-dihydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:16093)
• cholesterol + reduced [NADPH–hemoprotein reductase] + O2 = 7alpha-hydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:21812)
• 4beta-hydroxycholesterol + reduced [NADPH–hemoprotein reductase] + O2 = 4beta,7alpha-dihydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46120)
• (24S)-hydroxycholesterol + reduced [NADPH–hemoprotein reductase] + O2 = (24S)-7alpha-dihydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46124)
• 7-dehydrocholesterol + reduced [NADPH–hemoprotein reductase] + O2 = 7-oxocholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53248)
• lathosterol + reduced [NADPH–hemoprotein reductase] + O2 = 5alpha-cholestan-7-oxo-3beta-ol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53252)
• lathosterol + reduced [NADPH–hemoprotein reductase] + O2 = 7alpha,8alpha-epoxy-5alpha-cholestan-3beta-ol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53256)

UniProt features (53 total): helix 24, strand 17, sequence variant 4, turn 4, chain 1, transmembrane region 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3V8D	X-RAY DIFFRACTION	1.9
3DAX	X-RAY DIFFRACTION	2.15
3SN5	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22680-F1	95.04	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 444 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-192105	Synthesis of bile acids and bile salts
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781	PPARA activates gene expression
R-HSA-211976	Endogenous sterols

MSigDB gene sets: 231 (showing top): GOBP_RESPONSE_TO_ETHANOL, REACTOME_BIOLOGICAL_OXIDATIONS, HNF3ALPHA_Q6, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, REACTOME_ENDOGENOUS_STEROLS, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ALCOHOL_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS, LEE_LIVER_CANCER_CIPROFIBRATE_DN

GO Biological Process (15): bile acid biosynthetic process (GO:0006699), cholesterol catabolic process (GO:0006707), sterol metabolic process (GO:0016125), negative regulation of collagen biosynthetic process (GO:0032966), cholesterol homeostasis (GO:0042632), response to ethanol (GO:0045471), positive regulation of cholesterol biosynthetic process (GO:0045542), negative regulation of fatty acid biosynthetic process (GO:0045717), regulation of bile acid biosynthetic process (GO:0070857), cellular response to glucose stimulus (GO:0071333), cellular response to cholesterol (GO:0071397), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), small molecule metabolic process (GO:0044281)

GO Molecular Function (8): iron ion binding (GO:0005506), cholesterol 7-alpha-monooxygenase activity (GO:0008123), heme binding (GO:0020037), 24S-hydroxycholesterol 7-alpha-hydroxylase activity (GO:0033782), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), intracellular membrane-bounded organelle (GO:0043231), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Synthesis of bile acids and bile salts	2
Bile acid and bile salt metabolism	1
Regulation of lipid metabolism by PPARalpha	1
Cytochrome P450 - arranged by substrate type	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid 7-alpha-hydroxylase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	2
oxidoreductase activity	2
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
cholesterol metabolic process	1
sterol catabolic process	1
alcohol catabolic process	1
steroid metabolic process	1
negative regulation of biosynthetic process	1
negative regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
sterol homeostasis	1
response to alcohol	1
cholesterol biosynthetic process	1
regulation of cholesterol biosynthetic process	1
positive regulation of cholesterol metabolic process	1
positive regulation of sterol biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
fatty acid biosynthetic process	1
regulation of fatty acid biosynthetic process	1
negative regulation of fatty acid metabolic process	1
negative regulation of lipid biosynthetic process	1
bile acid biosynthetic process	1
regulation of ketone metabolic process	1
regulation of steroid biosynthetic process	1
regulation of small molecule metabolic process	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
cellular response to sterol	1
response to cholesterol	1
cellular response to alcohol	1
primary metabolic process	1
lipid metabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
metabolic process	1
transition metal ion binding	1

Protein interactions and networks

STRING

2612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP7A1	NR1H4	Q96RI1	975
CYP7A1	NR0B2	Q15466	969
CYP7A1	CYP27A1	Q02318	945
CYP7A1	NPC1L1	Q9UHC9	935
CYP7A1	ABCB11	O95342	925
CYP7A1	HMGCR	P04035	909
CYP7A1	SLC51A	Q86UW1	902
CYP7A1	NR5A2	O00482	902
CYP7A1	SLC10A1	Q14973	888
CYP7A1	ABCG5	Q9H222	887
CYP7A1	XPR1	Q9UBH6	884
CYP7A1	SCARB1	Q8WTV0	874
CYP7A1	NR1H3	Q13133	868
CYP7A1	SLC10A2	Q12908	867
CYP7A1	ABCG8	Q9H221	863

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A098DJ84, A0A0L1JEW4, A0A1V1FNZ5, B8N2C8, B8NFL5, B8NUK6, E9QY26, F1SYB2, F6H9N6, I1RBR4, I1RE80, I1RJR2, I1S2M5, O13820, O14442, O23365, O46420, O46491, O64697, O64698, P0DXU9, P0DXV0, P10613, P10614, P14263, P18125, P22680, P46634, P49602, P50859, P51542, Q02315, Q078T0, Q09736, Q12664, Q16850, Q1JPY5, Q1T7C2, Q4PJW3, Q4R8S6

Diamond homologs: A0A084R1M6, A0A0E3D8K9, A0A0E3D8P0, A0A0E3D8P5, A0A0F7TN60, A0A0U4ZPJ7, A0A140JWT4, A0A140JWT6, A0A218NGS0, A0A3T0ZHK6, A0A455LLV8, A0A455LM27, A2A974, A4D9R2, A9JPE0, B1GVX2, B6H066, C8VN91, D1MX86, E1ACQ3, F1SY71, F1SY99, G4MWA8, J7FIP8, L0E307, L7WRY5, M1V8J8, M1V8K0, O23051, O34926, O88833, O94142, P08516, P10611, P22680, P24464, P51869, P78329, P98187, P9WEQ9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PPARGC1A	“up-regulates quantity by expression”	CYP7A1	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	CYP7A1	“transcriptional regulation”
DBP	“up-regulates quantity by expression”	CYP7A1	“transcriptional regulation”
TFEB	“up-regulates quantity by expression”	CYP7A1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

251 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	169
Likely benign	52
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1070878	NM_000780.4(CYP7A1):c.959del (p.Glu320fs)	Pathogenic

SpliceAI

554 predictions. Top by Δscore:

Variant	Effect	Δscore
8:58492348:CTTA:C	donor_loss	1.0000
8:58492349:TTACC:T	donor_loss	1.0000
8:58492350:TA:T	donor_loss	1.0000
8:58492351:A:AC	donor_gain	1.0000
8:58492352:C:CT	donor_gain	1.0000
8:58492352:CCAA:C	donor_gain	1.0000
8:58492525:CTAT:C	acceptor_gain	1.0000
8:58492526:TAT:T	acceptor_gain	1.0000
8:58492527:AT:A	acceptor_gain	1.0000
8:58492530:T:G	acceptor_loss	1.0000
8:58492535:A:C	acceptor_gain	1.0000
8:58492536:T:C	acceptor_gain	1.0000
8:58492538:T:C	acceptor_gain	1.0000
8:58492538:T:TC	acceptor_gain	1.0000
8:58494502:CCA:C	donor_loss	1.0000
8:58494503:CA:C	donor_loss	1.0000
8:58494504:A:AC	donor_gain	1.0000
8:58494505:C:A	donor_loss	1.0000
8:58494505:C:CC	donor_gain	1.0000
8:58494632:GGTTC:G	acceptor_gain	1.0000
8:58494633:GTTC:G	acceptor_gain	1.0000
8:58494634:TTC:T	acceptor_gain	1.0000
8:58494635:TC:T	acceptor_gain	1.0000
8:58494636:CC:C	acceptor_gain	1.0000
8:58494637:C:CC	acceptor_gain	1.0000
8:58494637:C:T	acceptor_gain	1.0000
8:58494639:A:C	acceptor_gain	1.0000
8:58494640:T:C	acceptor_gain	1.0000
8:58494640:T:TC	acceptor_gain	1.0000
8:58494647:G:C	acceptor_gain	1.0000

AlphaMissense

3362 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:58492503:C:A	R355S	0.996
8:58492503:C:G	R355S	0.996
8:58492504:C:G	R355T	0.996
8:58492513:T:A	E352V	0.995
8:58496645:G:C	N289K	0.995
8:58496645:G:T	N289K	0.995
8:58496662:A:G	W284R	0.995
8:58496662:A:T	W284R	0.995
8:58491679:A:C	F437L	0.994
8:58491679:A:T	F437L	0.994
8:58491681:A:G	F437L	0.994
8:58496621:A:C	S297R	0.994
8:58496621:A:T	S297R	0.994
8:58496623:T:G	S297R	0.994
8:58497066:A:G	L149P	0.994
8:58492504:C:A	R355M	0.993
8:58496808:C:G	R235P	0.993
8:58491758:C:A	R411M	0.992
8:58492477:C:G	R364P	0.992
8:58496626:A:G	W296R	0.992
8:58496626:A:T	W296R	0.992
8:58496627:G:C	F295L	0.992
8:58496627:G:T	F295L	0.992
8:58496629:A:G	F295L	0.992
8:58498349:A:C	F67L	0.992
8:58498349:A:T	F67L	0.992
8:58498351:A:G	F67L	0.992
8:58491660:A:G	C444R	0.991
8:58492494:A:C	S358R	0.991
8:58492494:A:T	S358R	0.991

dbSNP variants (sampled 300 via entrez): RS1000535768 (8:58499115 A>G), RS1000891840 (8:58492795 C>T), RS1001597648 (8:58499712 T>G), RS1001975441 (8:58501308 A>G), RS1002500178 (8:58495177 A>G), RS1002567960 (8:58498508 A>G), RS1002730107 (8:58493016 C>T), RS1003171163 (8:58492640 C>G), RS1003222261 (8:58490210 C>A), RS1003369754 (8:58496621 A>G), RS1003600453 (8:58490508 C>G), RS1004205004 (8:58491959 G>T), RS1004883046 (8:58494036 G>A,T), RS1004963084 (8:58500127 G>A,T), RS1005383968 (8:58499764 T>C)

Disease associations

OMIM: gene MIM:118455 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency	Supportive	Semidominant

Mondo (1): hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency (MONDO:0016203)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0001396	Cholestasis
HP:0001397	Hepatic steatosis
HP:0001403	Macrovesicular hepatic steatosis
HP:0001513	Obesity
HP:0001677	Coronary artery atherosclerosis
HP:0002155	Hypertriglyceridemia
HP:0003124	Hypercholesterolemia
HP:0003141	Increased LDL cholesterol concentration
HP:0004943	Accelerated atherosclerosis
HP:0006573	Acute hepatic steatosis
HP:0008372	Abnormal circulating vitamin A concentration
HP:0011980	Cholesterol gallstones
HP:0012115	Hepatitis
HP:0012397	Aortic atherosclerotic lesion
HP:0100514	Abnormal circulating vitamin E concentration

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000759_10	LDL cholesterol	4.000000e-09
GCST000760_47	Cholesterol, total	9.000000e-13
GCST002221_17	Cholesterol, total	9.000000e-12
GCST002222_58	LDL cholesterol	1.000000e-07
GCST002896_28	Cholesterol, total	3.000000e-11
GCST002898_39	LDL cholesterol	2.000000e-11
GCST003725_5	Gallstone disease	3.000000e-06
GCST004233_49	LDL cholesterol levels	4.000000e-19
GCST004235_30	Total cholesterol levels	8.000000e-26
GCST006004_14	Low density lipoprotein cholesterol levels	9.000000e-09
GCST006034_36	Total cholesterol levels	5.000000e-18
GCST007209_25	Gallstone disease	1.000000e-25
GCST009365_61	LDL cholesterol levels x short total sleep time interaction (2df test)	3.000000e-14
GCST010243_185	Apolipoprotein B levels	7.000000e-40
GCST010244_53	Triglyceride levels	6.000000e-36
GCST010245_182	LDL cholesterol levels	3.000000e-46
GCST011346_55	Total cholesterol levels	2.000000e-18
GCST011347_32	Low density lipoprotein cholesterol levels	4.000000e-16
GCST90013407_67	Liver enzyme levels (gamma-glutamyl transferase)	5.000000e-24

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1851 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3808607	Efficacy	3	atorvastatin

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3808607	CYP7A1	3	5.25	1	atorvastatin

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP5, CYP7 and CYP8 families

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
(2S,4S)-ketoconazole	Inhibition	9.7	pIC50

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.06	IC50	880	nM	CHEMBL4289930
5.86	IC50	1370	nM	CHEMBL4288256
5.68	Kd	2100	nM	CHEMBL5574621

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1S,2S,5S,6S,9S,10R)-16-bis(tert-butylamino)phosphoryl-1,5-dimethyl-17,18-diazapentacyclo[11.8.0.02,10.05,9.015,20]henicosa-15,17,19-trien-6-ol	2110321: Binding affinity to recombinant human CYP7A1 assessed as substrate-type binding by measuring dissociation constant by spectrophotometric titration method	kd	2.1000	uM

CTD chemical–gene interactions

167 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	affects cotreatment, decreases expression, increases expression	9
Chenodeoxycholic Acid	affects binding, increases activity, decreases reaction, affects cotreatment, decreases expression	9
perfluorooctane sulfonic acid	affects cotreatment, decreases expression, increases expression	7
Rifampin	affects cotreatment, increases expression, decreases expression, increases reaction, decreases reaction	7
Cholesterol	decreases reaction, increases phosphorylation, increases abundance, affects metabolic processing, increases metabolic processing	5
Deoxycholic Acid	affects cotreatment, decreases expression	5
Cyclosporine	affects cotreatment, decreases expression, affects abundance	5
Bile Acids and Salts	decreases expression, increases abundance, increases chemical synthesis	4
Aflatoxin B1	decreases expression, affects expression	4
tebuconazole	decreases expression	3
perfluoro-n-nonanoic acid	affects cotreatment, decreases expression	3
Acetaminophen	decreases reaction, affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	affects cotreatment, decreases expression, decreases methylation	3
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	3
Glycocholic Acid	affects cotreatment, decreases expression	3
Glycodeoxycholic Acid	affects cotreatment, decreases expression	3
Triclosan	affects cotreatment, decreases expression, affects expression	3
lasiocarpine	decreases expression	2
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	2
enilconazole	decreases expression	2
pregna-4,17-diene-3,16-dione	decreases expression, decreases reaction, increases expression	2
propiconazole	decreases expression	2
cyproconazole	decreases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, decreases expression	2
obeticholic acid	decreases expression	2
perfluorohexanesulfonic acid	decreases expression, affects cotreatment	2
lithocholic acid acetate	increases activity, affects cotreatment, increases expression, decreases expression, decreases reaction (+2 more)	2
Rosiglitazone	decreases expression	2
Bezafibrate	decreases activity, decreases expression	2
Cadmium	increases abundance, increases expression, increases response to substance, decreases expression	2

ChEMBL screening assays

4 unique, capped per target: 3 admet, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4257181	Binding	Inhibition of CYP7A (unknown origin) assessed as reduction in bile acid secretion	Novel cytochrome p450 inhibitors and their method of use
CHEMBL4257203	ADMET	Inhibition of CYP7A (unknown origin) assessed as reduction in bile acid secretion	Novel functionalized 5-(phenoxymethyl)-1,3-dioxane analogs exhibiting cytochrome p450 inhibition and their method of use

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.