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HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
HMGCR (3-Hydroxy-3-Methylglutaryl-CoA Reductase) is a Protein Coding gene. Diseases associated with HMGCR include Familial Hypercholesterolemia and Familial Hyperlipidemia. Among its related pathways are Sterol Regulatory Element-Binding Proteins (SREBP) signalling and Terpenoid backbone biosynthesis. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and NADP binding.
3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) catalyzes the rate limiting step in cholesterol biosynthesis - conversion of 3-hydroxy-3-methyl-glutaryl-CoA to mevalonic acid. HMG-CoA reductase is a transmembrane enzyme, bound to endoplasmic reticulum.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004420 | hydroxymethylglutaryl-CoA reductase (NADPH) activity | IEA,IBA | 21873635 |
GO:0005515 | protein binding | IPI | 23169578 |
GO:0016491 | oxidoreductase activity | IEA | -- |
GO:0016616 | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA | -- |
GO:0042282 | hydroxymethylglutaryl-CoA reductase activity | IDA | 2991281 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005778 | peroxisomal membrane | IBA,IDA | 17180682 |
GO:0005783 | endoplasmic reticulum | IEA,IDA | 17180682 |
GO:0005789 | endoplasmic reticulum membrane | IBA,TAS | 2991281 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Terpenoid backbone biosynthesis | ||
2 | AMP-activated Protein Kinase (AMPK) Signaling | ||
3 | Metabolism |
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4 | Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) | ||
5 | Statin Pathway |
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GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006629 | lipid metabolic process | IEA | -- |
GO:0006694 | steroid biosynthetic process | IEA | -- |
GO:0006695 | cholesterol biosynthetic process | IDA,TAS | -- |
GO:0006743 | ubiquinone metabolic process | IEA | -- |
GO:0007568 | aging | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Lovastatin | Approved, Investigational | Pharma | Inhibitor, Competitive, Agonist, Full agonist, Target, inhibitor | HMG-CoA reductase inhibitor, Potent HMG-CoA reductase inhibitor | 82 | |
Pravastatin | Approved | Pharma | Inhibitor, Competitive, Target, inhibitor | 167 | ||
Simvastatin | Approved | Pharma | Inhibitor, Competitive, Target, inhibitor | HMG-CoA reductase inhibitor | 582 | |
Fluvastatin | Approved | Pharma | Inhibitor, Competitive, Target, inhibitor | HMGCR inhibitor | 0 | |
Atorvastatin | Approved | Pharma | Inhibitor, Competitive, Target, inhibitor | 893 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
3-hydroxy-3-methylglutaryl-coa |
|
1553-55-5 | ||||
6-Hydroxyfluvastatin |
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Hydrogen Ion |
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Pravastatin sodium salt |
|
81131-70-6 |
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|
Compound | Action | Cas Number |
---|---|---|
Fluvastatin sodium | Potent HMG-CoA reductase inhibitor | 93957-55-2 |
Lovastatin | Potent HMG-CoA reductase inhibitor | 75330-75-5 |
Mevastatin | HMG-CoA reductase inhibitor | 73573-88-3 |
Pravastatin sodium salt | HMG-CoA reductase inhibitor | 81131-70-6 |
Simvastatin | HMG-CoA reductase inhibitor | 79902-63-9 |
Compound | Action | Cas Number |
---|---|---|
Atorvastatin Calcium | HMG-CoA reductase inhibitor | 134523-03-8 |
Clinofibrate | HMGCR inhibitor | 30299-08-2 |
Fluvastatin | HMGCR inhibitor | 93957-54-1 |
Fluvastatin Sodium | HMG-CoA reductase inhibitor | 93957-55-2 |
Lovastatin | HMG-CoA reductase inhibitor | 75330-75-5 |
Mevastatin | HMG-CoA reductase inhibitor | 73573-88-3 |
Pitavastatin | HMG-CoA reductase inhibitor | 147511-69-1 |
Pitavastatin Calcium | Enzyme HMGCR inhibitor | 147526-32-7 |
Pravastatin | 81093-37-0 | |
Pravastatin sodium | HMG-CoA reductase inhibitor,highly selective and competitive | 81131-70-6 |
Rosuvastatin | 287714-41-4 | |
Rosuvastatin Calcium | 147098-20-2 | |
Simvastatin (Zocor) | HMGCR (HMG-CoA reductase) inhibitor | 79902-63-9 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7a | · | 7b | ^ | 8 | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 | ^ | 16a | · | 16b | ^ | 17 | ^ | 18a | · | 18b | ^ | 19a | · | 19b | ^ | 20a | · | 20b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | HMGCR 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | HMGCR 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | HMGCR 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | HMGCR 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | HMGCR 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Hmgcr 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Hmgcr 30 |
|
||
Chicken (Gallus gallus) |
Aves | HMGCR 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | HMGCR 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | hmgcr 30 |
|
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Str.16151 30 |
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African clawed frog (Xenopus laevis) |
Amphibia | LOC397750 30 |
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Zebrafish (Danio rerio) |
Actinopterygii | hmgcrb 31 |
|
OneToMany | |
hmgcra 30 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | Hmgcr 30 31 32 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP002288 30 |
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Worm (Caenorhabditis elegans) |
Secernentea | hmgr-1 30 31 |
|
OneToOne | |
F08F8.2 32 |
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Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | HMG2 30 31 |
|
OneToMany | |
HMG1 31 33 |
|
OneToMany | |||
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0B04642g 30 |
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A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_AER152W 30 |
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Thale Cress (Arabidopsis thaliana) |
eudicotyledons | HMG1 30 |
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Alicante grape (Vitis vinifera) |
eudicotyledons | Vvi.10817 30 |
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Soybean (Glycine max) |
eudicotyledons | Gma.4589 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os08g0512700 30 |
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Os.164 30 |
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Barley (Hordeum vulgare) |
Liliopsida | Hv.5593 30 |
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Wheat (Triticum aestivum) |
Liliopsida | Ta.1571 30 |
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Corn (Zea mays) |
Liliopsida | Zm.2360 30 |
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Bread mold (Neurospora crassa) |
Ascomycetes | NCU00712 30 |
|
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Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | hmg1 30 |
|
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Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne | |
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.2237 30 |
|
SNP ID | Clinical significance and condition | Chr 05 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs12654264 | Association: Low density lipoprotein cholesterol level quantitative trait locus 3 | 75,352,778(+) | A/T | INTRON_VARIANT | |
rs17244841 | Drug Response: HMG CoA reductase inhibitors response - Efficacy; pravastatin response - Efficacy; simvastatin response - Efficacy | 75,347,030(+) | A/T | INTRON_VARIANT | |
rs5908 | - | p.Ile638Val |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3304309 | CNV | mobile element insertion | 20981092 |
esv3575856 | CNV | gain | 25503493 |
Disorder | Aliases | PubMed IDs |
---|---|---|
familial hypercholesterolemia |
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familial hyperlipidemia |
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sitosterolemia |
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cerebrotendinous xanthomatosis |
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smith-lemli-opitz syndrome |
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