Protein / target
3-hydroxy-3-methylglutaryl-coenzyme A reductase
Protein at a glance
Biological role
Hydroxymethylglutaryl-CoA reductase (NADPH) activity
Primary system
Endocrine & metabolic
Strongest disease association
Hypercholesterolemia
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
15 approved
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis (PubMed:21357570, PubMed:2991281, PubMed:36745799, PubMed:6995544). HMGCR is the main target of statins, a class of cholesterol-lowering drugs (PubMed:11349148, PubMed:18540668, PubMed:36745799)
Subcellular location
Domains and Gene Ontology detail (22)Hide
Domains & features
Gene Ontology
- Ccytoplasmic side of endoplasmic reticulum membrane
- Cendoplasmic reticulum
- Cendoplasmic reticulum membrane
- Cperoxisomal membrane
- Fcoenzyme A binding
- FGTPase regulator activity
- Fhydroxymethylglutaryl-CoA reductase (NADPH) activity
- FNADPH binding
- Pcholesterol biosynthetic process
- Pcholesterol biosynthetic process via desmosterol
- Pcholesterol biosynthetic process via lathosterol
- Pcoenzyme A metabolic process
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·PPARA activates gene expression
- ·Activation of gene expression by SREBF (SREBP)
Metabolic enzyme activity
- ·coenzyme A metabolic process
View underlying pathways (4)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
HMG-CoA reductase inhibitor
Appears in clinical studies involving Hypercholesterolemia, hyperlipidemia, coronary artery disorder, stroke disorder
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Show all associationsHide all associations
Open Targets ranks 1,080 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 16 total
cardiovascular disorder · inherited lipid metabolism disorder · intermittent vascular claudication
hyperlipoproteinemia type 3 · Hypercholesterolemia · familial hypercholesterolemia
Hypercholesterolemia · coronary artery disorder · atherosclerosis
Hypercholesterolemia · cardiovascular disorder · Hypercholesterolemia
angina pectoris · hyperlipidemia · Hypercholesterolemia
Abnormal circulating lipid concentration · hyperlipidemia · Hypercholesterolemia
hyperlipidemia · Abnormal circulating lipid concentration
angina pectoris · Hypercholesterolemia · cardiovascular disorder
Hypercholesterolemia · Abnormal circulating lipid concentration · hyperlipidemia
cardiovascular disorder · familial hyperlipidemia · plasma cell myeloma
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
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 underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationEffect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial.
- New publicationAchievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT.
- New publicationEzetimibe Added to Statin Therapy after Acute Coronary Syndromes.
- Safety communication
Drug Safety Update: Simvastatin: increased risk of myopathy at high dose (80 mg)
- Safety communication
Drug Safety Update: Simvastatin: updated advice on drug interactions
- Safety communication
Drug Safety Update: Simvastatin: dose limitations with concomitant amlodipine or diltiazem
- New publicationEffect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial.
- New publicationA short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer.
- New publicationmTORC2 is required for proliferation and survival of TSC2-null cells.
- New publicationA pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction.
- New publicationSimvastatin as a treatment for pulmonary hypertension trial.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.