HMGCR

3-hydroxy-3-methylglutaryl-coenzyme A reductase UniProt accession P04035

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)

Source: UniProt

Homotetramer (PubMed:10698924). Homodimer (PubMed:10698924). Interacts (via its SSD) with INSIG1; the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway (PubMed:12535518, PubMed:19458199).

Interacts with UBIAD1 (PubMed:23169578)

Source: UniProt
Endoplasmic reticulum membrane — Multi-pass membrane protein, Peroxisome membrane — Multi-pass membrane protein
Source: UniProt

Ubiquitously expressed with the highest levels in the cerebellum, fetal brain, testis, skin and adrenal gland

Detected in the cerebellum, fetal brain, testis and adrenal gland

Low abundance except in skin, esophagus, and uterine cervix

Source: UniProt
  • Muscular dystrophy, limb-girdle, autosomal recessive 28 (LGMDR28)

    An autosomal recessive form of limb girdle muscular dystrophy, a group of genetically heterogeneous muscular disorders that share proximal muscle weakness as the major attribute. Most limb girdle muscular dystrophies present with elevated creatinine kinase and myopathic electromyographic features. Disease is usually progressive to a variable degree, ranging from minor disability to complete inability to ambulate, and can involve the large proximal muscles, as well as axial and facial muscles.

    Different disease forms may exhibit skeletal muscle hypertrophy, kyphoscoliosis, and contractures or involve other muscle groups and manifest with distal weakness, cardiomyopathy, dysphagia, and respiratory difficulties. LGMDR28 is characterized by progressive muscle weakness affecting the proximal and axial muscles of the upper and lower limbs, and highly variable age at onset. Most patients have limited ambulation or become wheelchair-bound within a few decades, and respiratory insufficiency commonly occurs.

Source: UniProt

Click a pathway to open the interactive Reactome viewer.

Pathway list and interactive viewer: Reactome

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to HMGCR, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 103

NCT ID Condition Brief Title Phase Status
NCT01483950 Hypercholesterolaemia Evaluation of Patients Treated With HMG-CoA Reductase Inhibitors to Reach Cholesterol Target Values N/A COMPLETED
NCT00361530 Ischemic Stroke Carotid Intima-media Thickness in Japan Statin Treatment Against Recurrent Stroke(J-STARS Echo) PHASE3 COMPLETED
NCT01894217 Hypercholesterolemia, HMG COA Reductase Inhibitor Adverse Reaction Statin Therapy to Improve Medication Adherence PHASE1 COMPLETED
NCT01013103 Coronary Artery Disease, HMG-CoA Reductase Inhibitor Toxicity, Atherosclerosis, Oxidative Stress, Endothelial Dysfunction Pleiotropic Effects of Atorvastatin in High Cardiovascular Risk Patients PHASE4 COMPLETED
NCT00303277 Alzheimer's Disease, Aging Do HMG CoA Reductase Inhibitors Affect Abeta Levels? PHASE4 COMPLETED
NCT03550859 Chronic Kidney Disease, Proteinuria HMG-CoA Reductase add-on in Chronic Kidney Disease Patients With Proteinuria PHASE4 UNKNOWN
NCT00233480 Heart Failure, Congestive Statin Therapy in Heart Failure: Potential Mechanisms of Benefit PHASE4 COMPLETED
NCT02859480 Coronary Artery Disease, Coronary Disease, Cardiovascular Diseases Dose-dependent Effect of Rosuvastatin on Long-term Clinical Outcomes After PCI PHASE4 UNKNOWN
NCT01212900 Atherosclerosis, Hypercholesterolemia Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression PHASE4 COMPLETED
NCT04776889 Prostate Cancer Metastatic The Prognosis of Lipid Reprogramming With Rosuvastatin, in Castrated Egyptian Prostate Cancer Patients PHASE4 COMPLETED