Hmgcr 3-hydroxy-3-methylglutaryl-Coenzyme A reductase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hmgcrprovided by MGI
Official Full Name: 3-hydroxy-3-methylglutaryl-Coenzyme A reductaseprovided by MGI
Primary source: MGI:MGI:96159
See related: Ensembl:ENSMUSG00000021670 AllianceGenome:MGI:96159
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Red; HMG-CoAR
Summary: Enables hydroxymethylglutaryl-CoA reductase (NADPH) activity. Involved in negative regulation of amyloid-beta clearance; negative regulation of protein catabolic process; and negative regulation of protein secretion. Acts upstream of or within cholesterol biosynthetic process; negative regulation of MAP kinase activity; and visual learning. Predicted to be located in endoplasmic reticulum. Predicted to be active in endoplasmic reticulum membrane and peroxisomal membrane. Is expressed in several structures, including autopod; branchial arch; central nervous system; forelimb bud; and ganglia. Human ortholog(s) of this gene implicated in several diseases, including asthma; coronary artery disease (multiple); dementia; diabetes mellitus (multiple); and neurodegenerative disease (multiple). Orthologous to human HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in CNS E18 (RPKM 39.9), CNS E11.5 (RPKM 30.5) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 13 D1; 13 50.65 cM

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	13	NC_000079.7 (96785470..96807444, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	13	NC_000079.6 (96648962..96670936, complement)

Chromosome 13 - NC_000079.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes.
Title: Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes.
Acetaldehyde Dehydrogenase 2 regulates HMG-CoA reductase stability and cholesterol synthesis in the liver.
Title: Acetaldehyde Dehydrogenase 2 regulates HMG-CoA reductase stability and cholesterol synthesis in the liver.
Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis.
Title: Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis.
It was concluded that reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity.
Title: Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice.
Myeloid cell Hmgcr drives atherosclerosis by promoting macrophage migration.
Title: Myeloid HMG-CoA (3-Hydroxy-3-Methylglutaryl-Coenzyme A) Reductase Determines Atherosclerosis by Modulating Migration of Macrophages.
Deletion of HMGCR expression in T cells led to a severe decrease in their numbers with the remaining cells displaying an activated phenotype, with an increased proportion of regulatory T cells (Tregs) in particular.
Title: HMG-CoA reductase promotes protein prenylation and therefore is indispensible for T-cell survival.
These results indicate that HIF-mediated induction of Insig-2 and degradation of HMGCR are physiologically relevant events that guard against wasteful oxygen consumption and inappropriate cell growth during hypoxia.
Title: Hypoxia-inducible factor 1α activates insulin-induced gene 2 (Insig-2) transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the liver.
these studies designate sterol-accelerated degradation of HMGCR as a potential therapeutic target for prevention of atherosclerosis and associated cardiovascular disease.
Title: Contribution of Accelerated Degradation to Feedback Regulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Cholesterol Metabolism in the Liver.
To eludicate the mechanisms underlying statin myotoxicity and HMGCR function in skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice.
Title: Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (2)
Targeted (6) 1 citation
Endonuclease-mediated (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Hmgcr (e-PCR), detects polymorphism
- UniSTS:546817

MARC_52793-52794:1149879463:1 (e-PCR)
- UniSTS:525340

NoName (e-PCR)
- UniSTS:224900

Hmgcr (e-PCR), detects polymorphism
- UniSTS:526740

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables GTPase regulator activity	IGI Inferred from Genetic Interaction more info	PubMed
enables NADP binding	IEA Inferred from Electronic Annotation more info
enables NADPH binding	ISO Inferred from Sequence Orthology more info
enables coenzyme A binding	ISO Inferred from Sequence Orthology more info
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 hydroxymethylglutaryl-CoA reductase (NADPH) activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IEA Inferred from Electronic Annotation more info
enables protein phosphatase 2A binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within cholesterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in coenzyme A metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryo development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in isoprenoid biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within long-term synaptic potentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of MAP kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of amyloid-beta clearance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of insulin secretion involved in cellular response to glucose stimulus	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of striated muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cardiac muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of skeletal muscle tissue development	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of smooth muscle cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of stress-activated MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vasoconstriction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of ERK1 and ERK2 cascade	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within steroid biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within steroid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in sterol biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in ubiquinone metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within visual learning	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
is_active_in endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in peroxisomal membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in peroxisomal membrane	ISO Inferred from Sequence Orthology more info
located_in peroxisome	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Names: 3-hydroxy-3-methylglutaryl-CoA reductase; HMG-CoA reductase

NP_001347094.1

EC 1.1.1.34

NP_001347095.1

EC 1.1.1.34

NP_032281.2

EC 1.1.1.34

XP_036013747.1

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.

mRNA and Protein(s)

NM_001360165.1 → NP_001347094.1 3-hydroxy-3-methylglutaryl-coenzyme A reductase isoform 1

Status: VALIDATED

Source sequence(s)

AC154851

Consensus CDS

CCDS26706.1

UniProtKB/Swiss-Prot

G3X8U5, Q01237, Q5U4I2

UniProtKB/TrEMBL

F2Z470

Conserved Domains (1) summary

TIGR00920
Location:1 → 887

2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
NM_001360166.1 → NP_001347095.1 3-hydroxy-3-methylglutaryl-coenzyme A reductase isoform 2

Status: VALIDATED

Source sequence(s)

AC154851

UniProtKB/TrEMBL

F2Z470

Conserved Domains (1) summary

TIGR00920
Location:11 → 897

2A060605; 3-hydroxy-3-methylglutaryl-coenzyme A reductase
NM_008255.2 → NP_032281.2 3-hydroxy-3-methylglutaryl-coenzyme A reductase isoform 1

See identical proteins and their annotated locations for NP_032281.2

Status: VALIDATED

Source sequence(s)

AC154851, AK048784, AK079302, AK159899, BM899288, BY124492

Consensus CDS

CCDS26706.1

UniProtKB/Swiss-Prot

G3X8U5, Q01237, Q5U4I2

UniProtKB/TrEMBL

F2Z470

Related

ENSMUSP00000022176.9, ENSMUST00000022176.15

Conserved Domains (1) summary

TIGR00920
Location:1 → 887

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

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000079.7 Reference GRCm39 C57BL/6J

Range

96785470..96807444 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036157854.1 → XP_036013747.1 3-hydroxy-3-methylglutaryl-coenzyme A reductase isoform X1

UniProtKB/Swiss-Prot

G3X8U5, Q01237, Q5U4I2

UniProtKB/TrEMBL

F2Z470

Conserved Domains (1) summary

TIGR00920
Location:1 → 887

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