Free for academic non-profit institutions. Other users need a Commercial license

Aliases for HMGCS2 Gene

Aliases for HMGCS2 Gene

  • 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 2 3 5
  • EC 4 56
  • 3-Hydroxy-3-Methylglutaryl-Coenzyme A Synthase 2 (Mitochondrial) 2
  • 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (Mitochondrial) 2
  • 3-Hydroxy-3-Methylglutaryl Coenzyme A Synthase 4
  • HMG-CoA Synthase 4

External Ids for HMGCS2 Gene

Previous GeneCards Identifiers for HMGCS2 Gene

  • GC01M120737
  • GC01M119128
  • GC01M119438
  • GC01M119637
  • GC01M120003
  • GC01M120092
  • GC01M120290
  • GC01M118149

Summaries for HMGCS2 Gene

Entrez Gene Summary for HMGCS2 Gene

  • 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]

GeneCards Summary for HMGCS2 Gene

HMGCS2 (3-Hydroxy-3-Methylglutaryl-CoA Synthase 2) is a Protein Coding gene. Diseases associated with HMGCS2 include 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency and Smith-Lemli-Opitz Syndrome. Among its related pathways are Terpenoid backbone biosynthesis and Ketone body metabolism. Gene Ontology (GO) annotations related to this gene include hydroxymethylglutaryl-CoA synthase activity. An important paralog of this gene is HMGCS1.

UniProtKB/Swiss-Prot for HMGCS2 Gene

  • This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

Additional gene information for HMGCS2 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HMGCS2 Gene

Genomics for HMGCS2 Gene

GeneHancer (GH) Regulatory Elements for HMGCS2 Gene

Promoters and enhancers for HMGCS2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01I119765 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE dbSUPER 555.5 +1.3 1318 4.5 ELF3 FOXA2 NFIB ARID4B ZNF195 THRB RAD21 RARA YY1 SCRT2 HMGCS2 HSD3BP5 LOC101929147 ADAM30 REG4 ZNF697 PIR35373 GC01P119741
GH01I119789 Enhancer 0.9 ENCODE dbSUPER 27.8 -21.8 -21757 2.4 ELF3 SOX13 TFAP4 FOXA2 TAF1 MAX RAD21 RARA YY1 GATA3 HMGCS2 REG4 ADAM30
GH01I119782 Enhancer 1.3 Ensembl ENCODE dbSUPER 16 -16.5 -16546 6.9 PKNOX1 FOXA2 RAD21 RFX5 RARA YY1 ZNF766 ZNF366 FOS RXRA PHGDH WARS2 REG4 HMGCS2 ADAM30 LOC101929147
GH01I119778 Enhancer 1.3 Ensembl ENCODE dbSUPER 15.8 -10.9 -10850 2.3 FOXA2 MLX YY1 FOS RXRA YY2 REST PPARG ZNF518A KAT8 HMGCS2 REG4
GH01I119772 Enhancer 1.2 Ensembl ENCODE dbSUPER 15.4 -5.5 -5457 4.2 BCOR FOXA2 TAF1 ZNF449 CHD4 MZF1 ZMYM3 ZNF384 YY1 ZNF664 HMGCS2 ADAM30 REG4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around HMGCS2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HMGCS2 gene promoter:

Genomic Locations for HMGCS2 Gene

Genomic Locations for HMGCS2 Gene
21,130 bases
Minus strand

Genomic View for HMGCS2 Gene

Genes around HMGCS2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HMGCS2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HMGCS2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HMGCS2 Gene

Proteins for HMGCS2 Gene

  • Protein details for HMGCS2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Hydroxymethylglutaryl-CoA synthase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • B7Z8R3
    • D3Y5K6
    • Q5SZU2
    • Q6IBF4

    Protein attributes for HMGCS2 Gene

    508 amino acids
    Molecular mass:
    56635 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for HMGCS2 Gene

    Alternative splice isoforms for HMGCS2 Gene


neXtProt entry for HMGCS2 Gene

Selected DME Specific Peptides for HMGCS2 Gene


Post-translational modifications for HMGCS2 Gene

  • Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-83 and Lys-310, inhibits the enzymatic activity.

Other Protein References for HMGCS2 Gene

Domains & Families for HMGCS2 Gene

Gene Families for HMGCS2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the HMG-CoA synthase family.
  • Belongs to the HMG-CoA synthase family.
genes like me logo Genes that share domains with HMGCS2: view

Function for HMGCS2 Gene

Molecular function for HMGCS2 Gene

GENATLAS Biochemistry:
3-hydroxy-3-methylglutaryl-CoA synthase 2,mitochondrial,first and regulating enzyme of ketogenic pathway,through association with PPARA
UniProtKB/Swiss-Prot CatalyticActivity:
Acetyl-CoA + H(2)O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA.
UniProtKB/Swiss-Prot Function:
This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

Enzyme Numbers (IUBMB) for HMGCS2 Gene

Phenotypes From GWAS Catalog for HMGCS2 Gene

Gene Ontology (GO) - Molecular Function for HMGCS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004421 hydroxymethylglutaryl-CoA synthase activity TAS --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with HMGCS2: view
genes like me logo Genes that share phenotypes with HMGCS2: view

Human Phenotype Ontology for HMGCS2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

Clone Products

No data available for Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for HMGCS2 Gene

Localization for HMGCS2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HMGCS2 Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HMGCS2 gene
Compartment Confidence
mitochondrion 5
peroxisome 2
cytosol 2
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for HMGCS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,TAS --
GO:0005743 mitochondrial inner membrane IEA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with HMGCS2: view

Pathways & Interactions for HMGCS2 Gene

genes like me logo Genes that share pathways with HMGCS2: view

UniProtKB/Swiss-Prot P54868-HMCS2_HUMAN

  • Pathway: Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.

Gene Ontology (GO) - Biological Process for HMGCS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0006694 steroid biosynthetic process IEA --
GO:0006695 cholesterol biosynthetic process IEA --
GO:0008152 metabolic process IEA --
GO:0008202 steroid metabolic process IEA --
genes like me logo Genes that share ontologies with HMGCS2: view

No data available for SIGNOR curated interactions for HMGCS2 Gene

Drugs & Compounds for HMGCS2 Gene

(3) Drugs for HMGCS2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
Acetoacetyl-CoA Experimental Pharma 0
Coenzyme A Investigational Nutra 0

(4) Additional Compounds for HMGCS2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • (S)-3-hydroxy-3-methylglutaryl-CoA
  • (S)-3-hydroxy-3-methylglutaryl-Coenzyme A
  • 3-Hydroxy-3-methyl-Glutaryl-CoA
  • 3-Hydroxy-3-methyl-Glutaryl-Coenzyme A
  • 3-Hydroxy-3-methylglutaryl-CoA
  • (-)-7-dehydrocholesterol
  • (3b)-Cholesta-5,7-dien-3-ol
  • (3beta)-Cholesta-5,7-dien-3-ol
  • 10,13-Dimethyl-17-(6-methylheptan-2-yl)-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
  • 17-(1,5-Dimethylhexyl)-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
  • Ac-CoA
  • Ac-Coenzyme A
  • Ac-S-CoA
  • Ac-S-Coenzyme A
  • Acetyl coenzyme-A
genes like me logo Genes that share compounds with HMGCS2: view

Transcripts for HMGCS2 Gene

Unigene Clusters for HMGCS2 Gene

3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial):
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HMGCS2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11a · 11b
SP1: - -
SP2: - - -
SP3: - -
SP4: - -

Relevant External Links for HMGCS2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HMGCS2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HMGCS2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HMGCS2 Gene

This gene is overexpressed in Liver (x32.3) and Colon - Transverse (x9.9).

Protein differential expression in normal tissues from HIPED for HMGCS2 Gene

This gene is overexpressed in Liver (39.1), Liver, secretome (8.5), and Fetal Liver (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for HMGCS2 Gene

NURSA nuclear receptor signaling pathways regulating expression of HMGCS2 Gene:


SOURCE GeneReport for Unigene cluster for HMGCS2 Gene:


mRNA Expression by UniProt/SwissProt for HMGCS2 Gene:

Tissue specificity: Expression in liver is 200-fold higher than in any other tissue. Low expression in colon, kidney, testis, and pancreas. Very low expression in heart and skeletal muscle. Not detected in brain. The relative expression of isoform 3 (at mRNA level) is highest in heart (70%) and skeletal muscle (60%).

Evidence on tissue expression from TISSUES for HMGCS2 Gene

  • Liver(4.9)
  • Nervous system(4.2)
  • Intestine(2.4)
  • Stomach(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HMGCS2 Gene

Germ Layers:
  • ectoderm
  • mesoderm
  • cardiovascular
  • endocrine
  • integumentary
  • nervous
Head and neck:
  • brain
  • ear
  • head
  • heart
  • adrenal gland
  • peripheral nerve
  • peripheral nervous system
  • skin
  • sweat gland
genes like me logo Genes that share expression patterns with HMGCS2: view

No data available for Protein tissue co-expression partners for HMGCS2 Gene

Orthologs for HMGCS2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HMGCS2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HMGCS2 33 34
  • 99.61 (n)
(Canis familiaris)
Mammalia HMGCS2 33 34
  • 88.39 (n)
(Bos Taurus)
Mammalia HMGCS2 33 34
  • 86.55 (n)
(Mus musculus)
Mammalia Hmgcs2 33 16 34
  • 86.35 (n)
(Rattus norvegicus)
Mammalia Hmgcs2 33
  • 85.56 (n)
(Monodelphis domestica)
Mammalia HMGCS2 34
  • 81 (a)
(Ornithorhynchus anatinus)
Mammalia HMGCS2 34
  • 71 (a)
(Gallus gallus)
Aves HMGCS2 33 34
  • 72.45 (n)
(Anolis carolinensis)
Reptilia HMGCS2 34
  • 68 (a)
fruit fly
(Drosophila melanogaster)
Insecta Hmgs 35 34
  • 60 (a)
(Caenorhabditis elegans)
Secernentea F25B4.6 35
  • 43 (a)
hmgs-1 34
  • 42 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ERG13 34
  • 43 (a)
(Oryza sativa)
Liliopsida Os.32782 33
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9481 34
  • 51 (a)
Species where no ortholog for HMGCS2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • zebrafish (Danio rerio)

Evolution for HMGCS2 Gene

Gene Tree for HMGCS2 (if available)
Gene Tree for HMGCS2 (if available)

Paralogs for HMGCS2 Gene

Paralogs for HMGCS2 Gene

(1) SIMAP similar genes for HMGCS2 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with HMGCS2: view

Variants for HMGCS2 Gene

Sequence variations from dbSNP and Humsavar for HMGCS2 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs137852636 pathogenic, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,764,211(-) A/G coding_sequence_variant, missense_variant
rs137852637 conflicting-interpretations-of-pathogenicity, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 119,753,304(-) G/A coding_sequence_variant, stop_gained
rs137852638 conflicting-interpretations-of-pathogenicity, pathogenic, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency, not provided, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,759,915(-) C/T coding_sequence_variant, intron_variant, missense_variant
rs137852639 pathogenic, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,750,830(-) C/T coding_sequence_variant, missense_variant
rs137852640 pathogenic, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,764,231(-) T/C coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for HMGCS2 Gene

Variant ID Type Subtype PubMed ID
nsv831215 CNV gain 17160897
nsv831204 CNV gain+loss 17160897
nsv524681 CNV gain 19592680
nsv428201 CNV gain 18775914

Variation tolerance for HMGCS2 Gene

Residual Variation Intolerance Score: 20.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.69; 32.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HMGCS2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HMGCS2 Gene

Disorders for HMGCS2 Gene

MalaCards: The human disease database

(2) MalaCards diseases for HMGCS2 Gene - From: HGMD, OMIM, ClinVar, Orphanet, Swiss-Prot, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards


  • 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911]: A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly. {ECO:0000269 PubMed:11228257, ECO:0000269 PubMed:11479731, ECO:0000269 PubMed:12647205}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for HMGCS2 Gene

defective ketogenesis with recurrent hypoketotic hypoglycemia during fasting

Additional Disease Information for HMGCS2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HMGCS2: view

Publications for HMGCS2 Gene

  1. Genetic basis of mitochondrial HMG-CoA synthase deficiency. (PMID: 11479731) Aledo R … Hegardt FG (Human genetics 2001) 3 4 22 58
  2. Molecular cloning and tissue expression of human mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. (PMID: 7893153) Mascaró C … Hegardt FG (Archives of biochemistry and biophysics 1995) 2 3 4 58
  3. Human mitochondrial HMG CoA synthase: liver cDNA and partial genomic cloning, chromosome mapping to 1p12-p13, and possible role in vertebrate evolution. (PMID: 7851882) Boukaftane Y … Mitchell GA (Genomics 1994) 2 3 4 58
  4. Characterization of splice variants of the genes encoding human mitochondrial HMG-CoA lyase and HMG-CoA synthase, the main enzymes of the ketogenesis pathway. (PMID: 21952825) Puisac B … Pié J (Molecular biology reports 2012) 3 4 58
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 44 58

Products for HMGCS2 Gene

Sources for HMGCS2 Gene

Loading form....