HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HMGCS2provided by HGNC
Official Full Name: 3-hydroxy-3-methylglutaryl-CoA synthase 2provided by HGNC
Primary source: HGNC:HGNC:5008
See related: Ensembl:ENSG00000134240 MIM:600234; AllianceGenome:HGNC:5008
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
Summary: The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting. Mutations in this gene are associated with HMG-CoA synthase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
Expression: Biased expression in liver (RPKM 471.6), colon (RPKM 127.8) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p12

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (119747996..119768932, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (119761239..119782165, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (120290619..120311555, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration promotes pulmonary fibrosis by activating fibroblasts.
Title: Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration promotes pulmonary fibrosis by activating fibroblasts.
HMGCS2 serves as a potential biomarker for inhibition of renal clear cell carcinoma growth.
Title: HMGCS2 serves as a potential biomarker for inhibition of renal clear cell carcinoma growth.
LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.
Title: LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.
Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis.
Title: Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis.
HMGCS2 in metabolic pathways was associated with overall survival in hepatocellular carcinoma: A LASSO-derived study.
Title: HMGCS2 in metabolic pathways was associated with overall survival in hepatocellular carcinoma: A LASSO-derived study.
Fructose drives mitochondrial metabolic reprogramming in podocytes via Hmgcs2-stimulated fatty acid degradation.
Title: Fructose drives mitochondrial metabolic reprogramming in podocytes via Hmgcs2-stimulated fatty acid degradation.
Epigenetic inactivation of hydroxymethylglutaryl CoA synthase reduces ketogenesis and facilitates tumor cell motility in clear cell renal carcinoma.
Title: Epigenetic inactivation of hydroxymethylglutaryl CoA synthase reduces ketogenesis and facilitates tumor cell motility in clear cell renal carcinoma.
PXR Suppresses PPARalpha-Dependent HMGCS2 Gene Transcription by Inhibiting the Interaction between PPARalpha and PGC1alpha.
Title: PXR Suppresses PPARα-Dependent HMGCS2 Gene Transcription by Inhibiting the Interaction between PPARα and PGC1α.
SLC38A4 functions as a tumour suppressor in hepatocellular carcinoma through modulating Wnt/beta-catenin/MYC/HMGCS2 axis.
Title: SLC38A4 functions as a tumour suppressor in hepatocellular carcinoma through modulating Wnt/β-catenin/MYC/HMGCS2 axis.
Expanding phenotypic and mutational spectra of mitochondrial HMG-CoA synthase deficiency.
Title: Expanding phenotypic and mutational spectra of mitochondrial HMG-CoA synthase deficiency.

Submit: New GeneRIF Correction See all GeneRIFs (32)

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
3-hydroxy-3-methylglutaryl-CoA synthase deficiency MedGen: C2751532 OMIM: 605911 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S3445 (e-PCR)
- UniSTS:47446

RH11689 (e-PCR)
- UniSTS:92645

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables hydroxymethylglutaryl-CoA synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables hydroxymethylglutaryl-CoA synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables hydroxymethylglutaryl-CoA synthase activity	ISS Inferred from Sequence or Structural Similarity more info
enables hydroxymethylglutaryl-CoA synthase activity	TAS Traceable Author Statement more info
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in acetyl-CoA metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in acetyl-CoA metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in adipose tissue development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to fatty acid	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucocorticoid stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cholesterol biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in farnesyl diphosphate biosynthetic process, mevalonate pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ketone body biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ketone body biosynthetic process	TAS Traceable Author Statement more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in midgut development	IEA Inferred from Electronic Annotation more info
involved_in multicellular organismal response to stress	IEA Inferred from Electronic Annotation more info
involved_in response to cAMP	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to glucagon	IEA Inferred from Electronic Annotation more info
involved_in response to growth hormone	IEA Inferred from Electronic Annotation more info
involved_in response to linoleic acid	IEA Inferred from Electronic Annotation more info
involved_in response to metal ion	IEA Inferred from Electronic Annotation more info
involved_in response to monosaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to prostaglandin F	IEA Inferred from Electronic Annotation more info
involved_in response to starvation	IEA Inferred from Electronic Annotation more info
involved_in response to temperature stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to testosterone	IEA Inferred from Electronic Annotation more info
involved_in response to triglyceride	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in mitochondrial matrix	TAS Traceable Author Statement more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: hydroxymethylglutaryl-CoA synthase, mitochondrial

Names: 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial); 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial); HMG-CoA synthase; testicular tissue protein Li 88

NP_001159579.1

EC 2.3.3.10

NP_005509.1

EC 2.3.3.10

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_013348.1 RefSeqGene

Range

5001..25937

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_447

mRNA and Protein(s)

NM_001166107.1 → NP_001159579.1 hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 2 precursor

See identical proteins and their annotated locations for NP_001159579.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) is missing an in-frame coding exon compared to variant 1. This results in a shorter isoform (2) lacking an internal protein segment compared to isoform 1.

Source sequence(s)

AI215948, AK303777, BC044217, BP420631, BX104280

Consensus CDS

CCDS53353.1

UniProtKB/Swiss-Prot

P54868

Related

ENSP00000439495.2, ENST00000544913.2

Conserved Domains (3) summary

TIGR01833
Location:50 → 464

HMG-CoA-S_euk; 3-hydroxy-3-methylglutaryl-CoA-synthase, eukaryotic clade

pfam08540
Location:187 → 464

HMG_CoA_synt_C; Hydroxymethylglutaryl-coenzyme A synthase C terminal

cl09938
Location:53 → 187

cond_enzymes; Condensing enzymes; Family of enzymes that catalyze a (decarboxylating or non-decarboxylating) Claisen-like condensation reaction. Members are share strong structural similarity, and are involved in the synthesis and degradation of fatty acids, and the ...
NM_005518.4 → NP_005509.1 hydroxymethylglutaryl-CoA synthase, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_005509.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AI215948, BC044217, BP420631, BX104280

Consensus CDS

CCDS905.1

UniProtKB/Swiss-Prot

B7Z8R3, D3Y5K6, P54868, Q5SZU2, Q6IBF4

UniProtKB/TrEMBL

A0A140VJL2

Related

ENSP00000358414.3, ENST00000369406.8

Conserved Domains (1) summary

TIGR01833
Location:50 → 506

HMG-CoA-S_euk; 3-hydroxy-3-methylglutaryl-CoA-synthase, eukaryotic clade