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

Gene ID: 3156, updated on 3-Apr-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
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Genomic context

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Location:
5q13.3
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (75336529..75362116)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (75817189..75843009)
105.20220307 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
  • 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. Novel polymorphism of the HMGCR gene related to the risk of diabetes in premature triple-vessel disease patients. Zhao X, et al. J Gene Med, 2022 Sep. PMID 35998373
  2. High-Risk Polymorphisms Associated with the Molecular Function of Human HMGCR Gene Infer the Inhibition of Cholesterol Biosynthesis. Das KC, et al. Biomed Res Int, 2022. PMID 35707384, Free PMC Article
  3. Mitochondrial dysfunction in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotising myopathy. Acosta IJ, et al. Neuromuscul Disord, 2022 May. PMID 35487868
  4. Effect of pH on structural dynamics of HMG-CoA reductase and binding affinity to β-sitosterol. Fatoki TH. J Biomol Struct Dyn, 2023 Jul. PMID 35470784
  5. Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series. Joseph VMK, et al. Clin Exp Rheumatol, 2022 Feb. PMID 35200125

See all (229) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Mitochondrial dysfunction in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotising myopathy.
    Title: Mitochondrial dysfunction in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotising myopathy.
Submit: New GeneRIF Correction See all GeneRIFs (131)

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_2023_10

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

Gene LinkOut

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