Protein / target

7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase

Encoded byCYP8B1Q9UNU6Homo sapiensSwiss-Prot

UniProt: Q9UNU6 Ensembl: ENSG00000180432 HGNC: HGNC:2653 NCBI Gene: 1582

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

Sterol 12-alpha-hydroxylase

Strongest disease association

Liver Diseases

Via encoding gene CYP8B1 · Genetic evidence · score 0.27

Research activity

Emerging research

1 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

View complete UniProt function annotation

Sterol 12-alpha-hydroxylase involved in primary bile acid biosynthesis by catalyzing the 12alpha-hydroxylation of key intermediates including 7alpha-hydroxycholest-4-en-3-one, 3alpha,7alpha-dihydroxy-5beta-cholestan-26-oate and chenodeoxycholate along the classic pathway (PubMed:10051404, PubMed:30465713, PubMed:39214664). May also hydroxylate 5beta-cholestane-3alpha,7alpha-diol (By similarity). Functions as a monooxygenase, inserting one atom of molecular oxygen into substrates while reducing the second to water, using electrons supplied by NADPH via cytochrome P450 reductase (CPR) (By similarity). Controls biliary balance of cholic acid and chenodeoxycholic acid, thereby regulating intestinal absorption of dietary lipids (By similarity)

Subcellular location

Endoplasmic reticulum membraneMicrosome membrane

Domains and Gene Ontology detail (11)

Gene Ontology

Cendoplasmic reticulum membrane
Fheme binding
Firon ion binding
Foxygen binding
Fsterol 12-alpha-hydroxylase activity
Pbile acid biosynthetic process
Ppositive regulation of intestinal cholesterol absorption
Presponse to cholesterol
Presponse to nutrient levels
Psteroid biosynthetic process
Psterol metabolic process

501 aa · 58 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GO

View supporting evidence

Lipid & lipoprotein metabolism

·Sterol 12-alpha-hydroxylase involved in primary bile acid biosynthesis by catalyzing the…
·sterol 12-alpha-hydroxylase activity
·positive regulation of intestinal cholesterol absorption
·response to cholesterol

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CYP8B1

Gene-level evidence surfaced through the gene CYP8B1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Liver Diseases

0.27Limited support

Genetic evidence dominant · Open Targets 0.16

Neurodegenerative Diseases

0.24Preliminary

Pathway evidence dominant · Open Targets 0.37 · no direct causal or clinical evidence

Progressive familial intrahepatic cholestasis

0.19Preliminary

Animal model evidence dominant · Open Targets 0.06 · no direct causal or clinical evidence

Carcinoma, Hepatocellular

0.13Preliminary

Literature evidence dominant · Open Targets 0.09 · no direct causal or clinical evidence

Neoplasms

0.10Preliminary

Literature evidence dominant · Open Targets 0.08 · no direct causal or clinical evidence

View evidence synthesis (5)

Liver DiseasesLimited support

0.27

agreement 0.13–0.41

Genetic98%Literature2%

Open Targets aggregate 0.16 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary

0.24

agreement 0.01–0.47

Pathway100%

Open Targets aggregate 0.37 · 1 independent evidence family · no direct causal or clinical evidence

Progressive familial intrahepatic cholestasisPreliminary

0.19

agreement 0.00–0.42

Animal model100%

Open Targets aggregate 0.06 · 1 independent evidence family · no direct causal or clinical evidence

Carcinoma, HepatocellularPreliminary

0.13

agreement 0.00–0.32

Literature83%RNA expression17%

Open Targets aggregate 0.09 · 2 independent evidence families · no direct causal or clinical evidence

NeoplasmsPreliminary

0.10

agreement 0.00–0.37

Literature100%

Open Targets aggregate 0.08 · 1 independent evidence family · no direct causal or clinical evidence

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Neurodegenerative Diseases0.37

Liver Diseases0.16

Carcinoma, Hepatocellular0.09

Neoplasms0.08

Progressive familial intrahepatic cholestasis0.06

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)

SM · Structure with LigandSM · High-Quality LigandAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.11 cites

Liu Y · Hepatology (Baltimore, Md.) · 2024

Recent

CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.

Liu Y · Hepatology (Baltimore, Md.) · 2024

Europe PMC papers linked directly to this protein.