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

Gene ID: 3156, updated on 8-Jan-2023

Summary

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
LDLCQ3
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

See HMGCR in Genome Data Viewer
Location:
5q13.3
Exon count:
23
Annotation release Status Assembly Chr Location
110 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (75336529..75362116)
110 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (75818061..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 uncharacterized LOC124901007 Neighboring gene ribosomal protein S26 pseudogene 26 Neighboring gene ceramide transporter 1 Neighboring gene DNA polymerase kappa Neighboring gene RNA, U7 small nuclear 175 pseudogene

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

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

HIV-1 interactions

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

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
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
PubMed 
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
PubMed 
involved_in negative regulation of MAP kinase activity 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 sterol biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
PubMed 
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
PubMed 
located_in peroxisomal membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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

NCBI Reference Sequences (RefSeq)

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_000859.3NP_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
    P04035, Q8N190
    UniProtKB/TrEMBL
    A0A024RAP2
    Related
    ENSP00000287936.4, ENST00000287936.9
    Conserved Domains (1) summary
    TIGR00920
    Location:1888
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
  2. NM_001130996.2NP_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/Swiss-Prot
    P04035
    Related
    ENSP00000340816.5, ENST00000343975.9
    Conserved Domains (1) summary
    TIGR00920
    Location:1835
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
  3. NM_001364187.1NP_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
    Q8N190
    UniProtKB/TrEMBL
    A0A024RAP2
    Related
    ENSP00000506232.1, ENST00000681410.1
    Conserved Domains (1) summary
    TIGR00920
    Location:1888
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...Open this link in a new tab

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_011543357.2XP_011541659.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X1

    UniProtKB/Swiss-Prot
    P04035
    Conserved Domains (3) summary
    cd00643
    Location:485891
    HMG-CoA_reductase_classI; Class I hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)
    TIGR00920
    Location:21908
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
    cl21543
    Location:108238
    MMPL; MMPL family
  2. XM_011543359.2XP_011541661.1  3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X3

    Conserved Domains (1) summary
    TIGR00920
    Location:21855
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
  3. XM_011543358.2XP_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
    P04035, Q8N190
    UniProtKB/TrEMBL
    A0A024RAP2
    Related
    ENSP00000505805.1, ENST00000681271.1
    Conserved Domains (1) summary
    TIGR00920
    Location:1888
    2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    75818061..75843009
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)