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: 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

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_000005.10 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?

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.
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.
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.
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.
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.
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.
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.
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.

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 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

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

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

XP_054208459.1

EC 1.1.1.34

XP_054208460.1

EC 1.1.1.34

XP_054208461.1

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

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
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
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

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/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
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
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

NC_060929.1 Alternate T2T-CHM13v2.0

Range

75817189..75843009

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054352484.1 → XP_054208459.1 3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X1
XM_054352486.1 → XP_054208461.1 3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X3
XM_054352485.1 → XP_054208460.1 3-hydroxy-3-methylglutaryl-Coenzyme A reductase isoform X2

UniProtKB/Swiss-Prot

B7Z3Y9, P04035, Q8N190