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    HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase [ Homo sapiens (human) ]

    Gene ID: 3156, updated on 2-Nov-2024

    Summary

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    Official Symbol
    HMGCRprovided by HGNC
    Official Full Name
    3-hydroxy-3-methylglutaryl-CoA reductaseprovided by HGNC
    Primary source
    HGNC:HGNC:5006
    See related
    Ensembl:ENSG00000113161 MIM:142910; AllianceGenome:HGNC:5006
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MYPLG; LDLCQ3; LGMDR28
    Summary
    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]
    Expression
    Ubiquitous expression in brain (RPKM 31.2), colon (RPKM 23.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HMGCR in Genome Data Viewer
    Location:
    5q13.3
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (75336529..75362116)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (75817189..75843009)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (74632993..74657941)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901006 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16101 Neighboring gene uncharacterized LOC124901007 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:74625905-74626062 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:74632956-74633516 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:74633517-74634075 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22679 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:74675495-74675665 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:74683071-74684270 Neighboring gene ribosomal protein S26 pseudogene 26 Neighboring gene ceramide transporter 1 Neighboring gene MPRA-validated peak5292 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:74723894-74724394 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:74724395-74724895 Neighboring gene MPRA-validated peak5293 silencer Neighboring gene MPRA-validated peak5294 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22680 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22681 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:74832057-74832255 Neighboring gene DNA polymerase kappa Neighboring gene RNA, U7 small nuclear 175 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein. Leichner GS, et al. J Biol Chem, 2011 Sep 16. PMID 21778231, Free PMC Article
    2. Increased hydroxymethylglutaryl coenzyme A reductase activity during respiratory syncytial virus infection mediates actin dependent inter-cellular virus transmission. Ravi LI, et al. Antiviral Res, 2013 Oct. PMID 23994498
    3. The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease. Akadam-Teker B, et al. Gene, 2013 Oct 10. PMID 23933271
    4. The increase in cholesterol levels at early stages after dengue virus infection correlates with an augment in LDL particle uptake and HMG-CoA reductase activity. Soto-Acosta R, et al. Virology, 2013 Aug 1. PMID 23642566
    5. 3-Hydroxyl-3-methylglutaryl-coenzyme A reductase is up regulated in hepatocellular carcinoma associated with paraneoplastic hypercholesterolemia. Sohda T, et al. Med Mol Morphol, 2013 Dec. PMID 23549978

    See all (239) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genetic Polymorphisms in the HMGCR Gene and Associations with Cognitive Decline in Parkinson's Disease Patients.
      Title: Genetic Polymorphisms in the HMGCR Gene and Associations with Cognitive Decline in Parkinson's Disease Patients.
    2. Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.
      Title: Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.
    3. Association of NPC1L1 and HMGCR gene polymorphisms with coronary artery calcification in patients with premature triple-vessel coronary disease.
      Title: Association of NPC1L1 and HMGCR gene polymorphisms with coronary artery calcification in patients with premature triple-vessel coronary disease.
    4. Early growth response 1 promoted the invasion of glioblastoma multiforme by elevating HMGB1.
      Title: Early growth response 1 promoted the invasion of glioblastoma multiforme by elevating HMGB1.
    5. Association between HMGCR, CRP, and CETP gene polymorphisms and metabolic/inflammatory serum profile in healthy adolescents.
      Title: Association between HMGCR, CRP, and CETP gene polymorphisms and metabolic/inflammatory serum profile in healthy adolescents.
    6. HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.
      Title: HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.
    7. Effect of pH on structural dynamics of HMG-CoA reductase and binding affinity to beta-sitosterol.
      Title: Effect of pH on structural dynamics of HMG-CoA reductase and binding affinity to β-sitosterol.
    8. Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone.
      Title: Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone.
    9. Novel polymorphism of the HMGCR gene related to the risk of diabetes in premature triple-vessel disease patients.
      Title: Novel polymorphism of the HMGCR gene related to the risk of diabetes in premature triple-vessel disease patients.
    10. High-Risk Polymorphisms Associated with the Molecular Function of Human HMGCR Gene Infer the Inhibition of Cholesterol Biosynthesis.
      Title: High-Risk Polymorphisms Associated with the Molecular Function of Human HMGCR Gene Infer the Inhibition of Cholesterol Biosynthesis.
    Submit: New GeneRIF Correction See all GeneRIFs (132)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Low density lipoprotein cholesterol level quantitative trait locus 3
    MedGen: C3888197 OMIM: 620410 GeneReviews: Not available
    		not available
    Muscular dystrophy, limb-girdle, autosomal recessive 28
    MedGen: C5830518 OMIM: 620375 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A genome wide association study identifies common variants associated with lipid levels in the Chinese population.
    EBI GWAS Catalog
    Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.
    EBI GWAS Catalog
    Biological, clinical and population relevance of 95 loci for blood lipids.
    EBI GWAS Catalog
    Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.
    EBI GWAS Catalog
    Common variants at 30 loci contribute to polygenic dyslipidemia.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
    EBI GWAS Catalog
    Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.
    EBI GWAS Catalog
    Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.
    EBI GWAS Catalog
    Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
    EBI GWAS Catalog
    Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef HIV-1 Nef modulates expression of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) in Jurkat cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase regulator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables NADPH binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables coenzyme A binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables hydroxymethylglutaryl-CoA reductase (NADPH) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables hydroxymethylglutaryl-CoA reductase (NADPH) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cholesterol biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in coenzyme A metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in isoprenoid biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in long-term synaptic potentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of amyloid-beta clearance ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of protein catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of protein secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of ERK1 and ERK2 cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in sterol biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in visual learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in endoplasmic reticulum membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in peroxisomal membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in peroxisomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    3-hydroxy-3-methylglutaryl-Coenzyme A reductase
    Names
    3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
    HMG-CoA reductase
    hydroxymethylglutaryl-CoA reductase
    NP_000850.1
    NP_001124468.1
    NP_001351116.1
    XP_011541659.1
    XP_011541660.1
    XP_011541661.1
    XP_054208459.1
    XP_054208460.1
    XP_054208461.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011449.1 RefSeqGene

      Range
      5053..29934
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000859.3 → NP_000850.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 1

      See identical proteins and their annotated locations for NP_000850.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 3 both encode the same isoform (1).
      Source sequence(s)
      AA648735, BC033692, CN278665, M11058, M62627
      Consensus CDS
      CCDS4027.1
      UniProtKB/Swiss-Prot
      B7Z3Y9, P04035, Q8N190
      UniProtKB/TrEMBL
      A8KA27
      Related
      ENSP00000287936.4, ENST00000287936.9
      Conserved Domains (1) summary
      TIGR00920
      Location:1 → 888
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

    2. NM_001130996.2 → NP_001124468.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 2

      See identical proteins and their annotated locations for NP_001124468.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding exon in the middle region, as compared to variant 1. The resulting isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AA648735, BC033692, CN278665, M62627
      Consensus CDS
      CCDS47234.1
      UniProtKB/TrEMBL
      A8KA27
      Related
      ENSP00000340816.5, ENST00000343975.9
      Conserved Domains (1) summary
      TIGR00920
      Location:1 → 835
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

    3. NM_001364187.1 → NP_001351116.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1 and 3 both encode the same isoform (1).
      Source sequence(s)
      AC008897
      Consensus CDS
      CCDS4027.1
      UniProtKB/Swiss-Prot
      B7Z3Y9, P04035, Q8N190
      UniProtKB/TrEMBL
      A8KA27
      Related
      ENSP00000506232.1, ENST00000681410.1
      Conserved Domains (1) summary
      TIGR00920
      Location:1 → 888
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      75336529..75362116
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011543357.2 → XP_011541659.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X1

      UniProtKB/TrEMBL
      A8KA27
      Conserved Domains (3) summary
      cd00643
      Location:485 → 891
      HMG-CoA_reductase_classI; Class I hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)
      TIGR00920
      Location:21 → 908
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      cl21543
      Location:108 → 238
      MMPL; MMPL family

    2. XM_011543359.2 → XP_011541661.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X3

      UniProtKB/TrEMBL
      A8KA27
      Conserved Domains (1) summary
      TIGR00920
      Location:21 → 855
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

    3. XM_011543358.2 → XP_011541660.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X2

      See identical proteins and their annotated locations for XP_011541660.1

      UniProtKB/Swiss-Prot
      B7Z3Y9, P04035, Q8N190
      UniProtKB/TrEMBL
      A8KA27
      Related
      ENSP00000505805.1, ENST00000681271.1
      Conserved Domains (1) summary
      TIGR00920
      Location:1 → 888
      2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      75817189..75843009
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352484.1 → XP_054208459.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X1

    2. XM_054352486.1 → XP_054208461.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X3

    3. XM_054352485.1 → XP_054208460.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X2

      UniProtKB/Swiss-Prot
      B7Z3Y9, P04035, Q8N190
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P04035.1 GenPept UniProtKB/Swiss-Prot:P04035

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    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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