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
  • Cholesterol biosynthesis
  • PPARA activates gene expression
  • Activation of gene expression by SREBF (SREBP)
  • EGR2 and SOX10-mediated initiation of Schwann cell myelination
Source: Reactome via UniProt

Mutations

No mutation information available.

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
NCT01385631 ST-Segment Elevation Myocardial Infarction Ezetimibe In Addition To Atorvastatin Therapy On The Plaque Composition In Patients With Acute Myocardial Infarction. PHASE4 COMPLETED
NCT01894217 Hypercholesterolemia, HMG COA Reductase Inhibitor Adverse Reaction Statin Therapy to Improve Medication Adherence PHASE1 COMPLETED
NCT00345202 Healthy Short Term Effects of HMG-CoA Reductase Inhibition (Atorvastatin)on Renal Hemodynamics, Tubular Function and Vasoactive Hormones on Healthy Subjects PHASE4 COMPLETED
NCT00594191 Cirrhosis, Portal Hypertension Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension PHASE2 COMPLETED
NCT00920101 Atherosclerosis, Inflammation Anti-inflammatory Effect of Atorvastatin in Atherosclerotic Plaques Assessed by FDG-PET Imaging PHASE4 UNKNOWN
NCT00345657 Hyperlipidemia, Mixed Hyperlipidemia, Dyslipidemia Efficacy Study of Extended-Release Niacin/Lovastatin Versus Usual Care PHASE4 COMPLETED
NCT01200056 Coronary Disease, Ultrasonography, Interventional, Hydroxymethylglutaryl-CoA Reductase Inhibitors Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment PHASE4 COMPLETED
NCT01166633 Hypercholesterolemia Efficacy and Safety Study of Pitavastatin Versus Atorvastatin to Treat Hypercholesterolemia PHASE4 COMPLETED
NCT00233480 Heart Failure, Congestive Statin Therapy in Heart Failure: Potential Mechanisms of Benefit PHASE4 COMPLETED
NCT00797407 Hypercholesterolemia, Aches, Cramps, Weakness Effectiveness of Creatine in Preventing Muscle Aching From Cholesterol-Lowering Statin Drugs NA COMPLETED