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

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: mouse all
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Genomic context

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_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
Association of 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene polymorphism with obesity and lipid metabolism in children and adolescents with autism spectrum disorder.
Title: Association of 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene polymorphism with obesity and lipid metabolism in children and adolescents with autism spectrum disorder.
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series.
Title: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series.
Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease.
Title: Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease.
A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson's Disease.
Title: A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson's Disease.
Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-beta-treated epithelial cancer cells.
Title: Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells.
A-family anti-inflammatory cyclopentenone prostaglandins: A novel class of non-statin inhibitors of HMG-CoA reductase.
Title: A-family anti-inflammatory cyclopentenone prostaglandins: A novel class of non-statin inhibitors of HMG-CoA reductase.
Mesenchymal subtype neuroblastomas are addicted to TGF-betaR2/HMGCR-driven protein geranylgeranylation.
Title: Mesenchymal subtype neuroblastomas are addicted to TGF-βR2/HMGCR-driven protein geranylgeranylation.

Submit: New GeneRIF Correction See all GeneRIFs (124)

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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH47294 (e-PCR)
- UniSTS:36389

GDB:177804 (e-PCR)
- UniSTS:154965

GDB:181537 (e-PCR)
- UniSTS:155263

D5S2670 (e-PCR)
- UniSTS:67513

D5S2478 (e-PCR)
- UniSTS:8158

EST7D6 (e-PCR)
- UniSTS:263414

Homology

Homologs of the HMGCR gene: The HMGCR gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 420 organisms have orthologs with human gene HMGCR
Orthologs

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

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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

EC 1.1.1.34

NP_001124468.1

EC 1.1.1.34

NP_001351116.1

EC 1.1.1.34

XP_011541659.1

EC 1.1.1.34

XP_011541660.1

EC 1.1.1.34

XP_011541661.1

EC 1.1.1.34

NCBI Reference Sequences (RefSeq)

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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

NG_011449.1 RefSeqGene

Range

5053..29934

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

P04035, Q8N190

UniProtKB/TrEMBL

A0A024RAP2

Related

ENSP00000287936.4, ENST00000287936.9

Conserved Domains (1) summary

TIGR00920
Location:1 → 888

2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
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/Swiss-Prot

P04035

Related

ENSP00000340816.5, ENST00000343975.9

Conserved Domains (1) summary

TIGR00920
Location:1 → 835

2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
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

Q8N190

UniProtKB/TrEMBL

A0A024RAP2

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: Homo sapiens Annotation Release 110 details...

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

75336529..75362116

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

P04035

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

Conserved Domains (1) summary

TIGR00920
Location:21 → 855

2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
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

P04035, Q8N190

UniProtKB/TrEMBL

A0A024RAP2

Related

ENSP00000505805.1, ENST00000681271.1

Conserved Domains (1) summary

TIGR00920
Location:1 → 888

2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase