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Aliases for HMGCS2 Gene

Aliases for HMGCS2 Gene

  • 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 2 3 5
  • EC 2.3.3.10 4 61
  • 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 Hmg-Coa Synthase-2 Deficiency and Smith-Lemli-Opitz Syndrome. Among its related pathways are Validated targets of C-MYC transcriptional repression and Ketone body metabolism. 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.

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

Regulatory Elements for HMGCS2 Gene

Enhancers for HMGCS2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01G119789 1 ENCODE dbSUPER 27.8 -21.8 -21757 2.4 ELF3 SOX13 TFAP4 FOXA2 TAF1 TEAD4 MAX RAD21 RARA YY1 HMGCS2 REG4 ADAM30
GH01G119778 1.5 Ensembl ENCODE dbSUPER 15.8 -10.9 -10850 2.3 FOXA2 MLX YY1 FOS YY2 ZHX2 REST PPARG ZNF518A KAT8 HMGCS2 REG4
GH01G119782 1.4 Ensembl ENCODE dbSUPER 16 -16.5 -16546 6.9 PKNOX1 RAD21 RARA YY1 ZNF766 ZNF366 FOS U2AF2 CEBPB REST PHGDH REG4 HMGCS2 ADAM30 LOC101929147 WARS2
GH01G119772 1.3 Ensembl ENCODE dbSUPER 15.4 -5.5 -5457 4.2 BCOR FOXA2 TAF1 CHD4 ZMYM3 ZNF384 YY1 ZNF664 GATA3 SCRT2 HMGCS2 ADAM30 REG4
GH01G119793 0.5 dbSUPER 27.3 -25.8 -25844 2.0 ZFHX2 MAZ FOXA2 EGR2 HMGCS2 ADAM30 PHGDH ZNF697 REG4
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HMGCS2 on UCSC Golden Path with GeneCards custom track

Genomic Location for HMGCS2 Gene

Chromosome:
1
Start:
119,747,996 bp from pter
End:
119,769,125 bp from pter
Size:
21,130 bases
Orientation:
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:
    P54868-HMCS2_HUMAN
    Recommended name:
    Hydroxymethylglutaryl-CoA synthase, mitochondrial
    Protein Accession:
    P54868
    Secondary Accessions:
    • B7Z8R3
    • D3Y5K6
    • Q5SZU2
    • Q6IBF4

    Protein attributes for HMGCS2 Gene

    Size:
    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

    UniProtKB/Swiss-Prot:

neXtProt entry for HMGCS2 Gene

Selected DME Specific Peptides for HMGCS2 Gene

P54868:
  • RPTGGAGAVAML
  • VVCGDIA
  • LAGSRIGAFSYGSGLAASF
  • EVYFPAQYVDQT
  • SYGSGLAASFFSF
  • VDGKLSIQCYL
  • VQKSLAR
  • GNARPTGG
  • YGCLASLL
  • ESSSWDGRYA
  • EDINSLCLTVV
  • TNACYGGTA
  • MGFCSVQED
  • CYLRALD
  • MIFHTPFCK

Post-translational modifications for HMGCS2 Gene

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

Other Protein References for HMGCS2 Gene

Domains & Families for HMGCS2 Gene

Graphical View of Domain Structure for InterPro Entry

P54868

UniProtKB/Swiss-Prot:

HMCS2_HUMAN :
  • Belongs to the HMG-CoA synthase family.
Family:
  • Belongs to the HMG-CoA synthase family.
genes like me logo Genes that share domains with HMGCS2: view

No data available for Gene Families for HMGCS2 Gene

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

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

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry 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

Mitochondrion.

Subcellular locations from

COMPARTMENTS
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

Gene Ontology (GO) - Cellular Components for HMGCS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion TAS,IDA --
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 Nutra 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
3-hydroxy-3-methylglutaryl-coa
  • (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
1553-55-5
7-dehydrocholesterol
  • (-)-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
434-16-2
acetyl-coa
  • Ac-CoA
  • Ac-Coenzyme A
  • Ac-S-CoA
  • Ac-S-Coenzyme A
  • Acetyl coenzyme-A
72-89-9
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:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry 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: - -
SP5:

Relevant External Links for HMGCS2 Gene

GeneLoc Exon Structure for
HMGCS2
ECgene alternative splicing isoforms for
HMGCS2

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:

HMGCS2

SOURCE GeneReport for Unigene cluster for HMGCS2 Gene:

Hs.59889

mRNA Expression by UniProt/SwissProt for HMGCS2 Gene:

P54868-HMCS2_HUMAN
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
Systems:
  • cardiovascular
  • endocrine
  • integumentary
  • nervous
Organs:
Head and neck:
  • brain
  • ear
  • head
Thorax:
  • heart
Abdomen:
  • adrenal gland
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • sweat gland
genes like me logo Genes that share expression patterns with HMGCS2: view

Primer Products

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
chimpanzee
(Pan troglodytes)
Mammalia HMGCS2 34 35
  • 99.61 (n)
dog
(Canis familiaris)
Mammalia HMGCS2 34 35
  • 88.39 (n)
cow
(Bos Taurus)
Mammalia HMGCS2 34 35
  • 86.55 (n)
mouse
(Mus musculus)
Mammalia Hmgcs2 34 16 35
  • 86.35 (n)
rat
(Rattus norvegicus)
Mammalia Hmgcs2 34
  • 85.56 (n)
oppossum
(Monodelphis domestica)
Mammalia HMGCS2 35
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HMGCS2 35
  • 71 (a)
OneToOne
chicken
(Gallus gallus)
Aves HMGCS2 34 35
  • 72.45 (n)
lizard
(Anolis carolinensis)
Reptilia HMGCS2 35
  • 68 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Hmgs 36 35
  • 60 (a)
worm
(Caenorhabditis elegans)
Secernentea F25B4.6 36
  • 43 (a)
hmgs-1 35
  • 42 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ERG13 35
  • 43 (a)
OneToMany
rice
(Oryza sativa)
Liliopsida Os.32782 34
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9481 35
  • 51 (a)
OneToMany
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

ENSEMBL:
Gene Tree for HMGCS2 (if available)
TreeFam:
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 Sequence Context AA Info Type
rs137852636 Pathogenic, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,764,211(-) CCCTC(C/T)TCAAT reference, missense
rs137852638 other, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,759,915(-) GGGCC(A/G)GAGCT intron-variant, reference, missense
rs137852639 Pathogenic, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,750,830(-) GCATC(A/G)CCGAA reference, missense
rs137852640 Pathogenic, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,764,231(-) CTGCT(A/G)CGGTG reference, missense
rs28937320 Pathogenic, 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911] 119,764,571(-) AGGAC(A/G)TGGGC reference, missense

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

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

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)

Relevant External Links for HMGCS2 Gene

Human Gene Mutation Database (HGMD)
HMGCS2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HMGCS2

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: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
hmg-coa synthase-2 deficiency
  • 3-hydroxy-3-methylglutaryl-coa synthase-2 deficiency
smith-lemli-opitz syndrome
  • rutledge lethal multiple congenital anomaly syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

HMCS2_HUMAN
  • 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

Relevant External Links for HMGCS2

Genetic Association Database (GAD)
HMGCS2
Human Genome Epidemiology (HuGE) Navigator
HMGCS2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HMGCS2
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 F.G. (Hum. Genet. 2001) 3 4 22 64
  2. Molecular cloning and tissue expression of human mitochondrial 3- hydroxy-3-methylglutaryl-CoA synthase. (PMID: 7893153) Mascaro C. … Hegardt F.G. (Arch. Biochem. Biophys. 1995) 2 3 4 64
  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 G.A. (Genomics 1994) 2 3 4 64
  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. … Pie J. (Mol. Biol. Rep. 2012) 3 4 64
  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 S.D. … Anand S. (Diabetes Care 2010) 3 46 64

Products for HMGCS2 Gene

Sources for HMGCS2 Gene

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