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Aliases for HMGCL Gene

Aliases for HMGCL Gene

  • 3-Hydroxymethyl-3-Methylglutaryl-CoA Lyase 2 3 5
  • 3-Hydroxymethyl-3-Methylglutaryl-Coenzyme A Lyase 2 3
  • 3-Hydroxy-3-Methylglutarate-CoA Lyase 3 4
  • Hydroxymethylglutaricaciduria 2 3
  • HMG-CoA Lyase 3 4
  • EC 4.1.3.4 4 63
  • HL 3 4
  • Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Lyase 3
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase 3

External Ids for HMGCL Gene

Previous GeneCards Identifiers for HMGCL Gene

  • GC01M023686
  • GC01M023199
  • GC01M023597
  • GC01M023873
  • GC01M024001
  • GC01M024128
  • GC01M022379

Summaries for HMGCL Gene

Entrez Gene Summary for HMGCL Gene

  • The protein encoded by this gene belongs to the HMG-CoA lyase family. It is a mitochondrial enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Mutations in this gene are associated with HMG-CoA lyase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

GeneCards Summary for HMGCL Gene

HMGCL (3-Hydroxymethyl-3-Methylglutaryl-CoA Lyase) is a Protein Coding gene. Diseases associated with HMGCL include hmg-coa lyase deficiency and 3-hydroxy-3-methylglutaryl-coenzyme a lyase deficiency. Among its related pathways are Butanoate metabolism and Metabolism. GO annotations related to this gene include protein homodimerization activity and magnesium ion binding. An important paralog of this gene is HMGCLL1.

UniProtKB/Swiss-Prot for HMGCL Gene

  • Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism.

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

Genomics for HMGCL Gene

Regulatory Elements for HMGCL Gene

Enhancers for HMGCL Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HMGCL on UCSC Golden Path with GeneCards custom track

Promoters for HMGCL Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around HMGCL on UCSC Golden Path with GeneCards custom track

Genomic Location for HMGCL Gene

Chromosome:
1
Start:
23,801,877 bp from pter
End:
23,838,620 bp from pter
Size:
36,744 bases
Orientation:
Minus strand

Genomic View for HMGCL Gene

Genes around HMGCL on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HMGCL Gene

Proteins for HMGCL Gene

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

    Protein Symbol:
    P35914-HMGCL_HUMAN
    Recommended name:
    Hydroxymethylglutaryl-CoA lyase, mitochondrial
    Protein Accession:
    P35914
    Secondary Accessions:
    • B4DUP4
    • B7UCC6
    • D3Y5K7
    • Q6IBC0
    • Q96FP8

    Protein attributes for HMGCL Gene

    Size:
    325 amino acids
    Molecular mass:
    34360 Da
    Cofactor:
    Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
    Quaternary structure:
    • Homodimer; disulfide-linked. Can also form homotetramers.

    Three dimensional structures from OCA and Proteopedia for HMGCL Gene

    Alternative splice isoforms for HMGCL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HMGCL Gene

Proteomics data for HMGCL Gene at MOPED

Post-translational modifications for HMGCL Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HMGCL Gene

Domains & Families for HMGCL Gene

Protein Domains for HMGCL Gene

Graphical View of Domain Structure for InterPro Entry

P35914

UniProtKB/Swiss-Prot:

HMGCL_HUMAN :
  • Belongs to the HMG-CoA lyase family.
Family:
  • Belongs to the HMG-CoA lyase family.
genes like me logo Genes that share domains with HMGCL: view

No data available for Gene Families for HMGCL Gene

Function for HMGCL Gene

Molecular function for HMGCL Gene

GENATLAS Biochemistry:
3-hydroxy-3-methylglutaryl-CoA lyase,homodimeric mitochondrial and peroxisomal matrix enzyme,branched chain,last enzyme of ketogenesis from fatty acids and also leucine catabolism,lethal in HMGCL-deficient mice
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=200 uM for magnesium ion {ECO:0000269 PubMed:12874287, ECO:0000269 PubMed:15122894}; KM=48 uM for HMG-CoA {ECO:0000269 PubMed:12874287, ECO:0000269 PubMed:15122894}; Vmax=191 umol/min/mg enzyme {ECO:0000269 PubMed:12874287, ECO:0000269 PubMed:15122894};
UniProtKB/Swiss-Prot CatalyticActivity:
(S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Stimulated by reducing agents such as dithiothreitol (DTT).
UniProtKB/Swiss-Prot Function:
Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism.

Enzyme Numbers (IUBMB) for HMGCL Gene

Gene Ontology (GO) - Molecular Function for HMGCL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0005102 receptor binding IPI 20178365
GO:0030145 manganese ion binding IDA 9200711
GO:0031406 carboxylic acid binding IEA --
genes like me logo Genes that share ontologies with HMGCL: view
genes like me logo Genes that share phenotypes with HMGCL: view

Human Phenotype Ontology for HMGCL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HMGCL Gene

MGI Knock Outs for HMGCL:

Animal Model Products

miRNA for HMGCL Gene

miRTarBase miRNAs that target HMGCL

No data available for Transcription Factor Targets and HOMER Transcription for HMGCL Gene

Localization for HMGCL Gene

Subcellular locations from UniProtKB/Swiss-Prot for HMGCL Gene

Mitochondrion matrix. Peroxisome. Note=Unprocessed form is peroxisomal.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HMGCL Gene COMPARTMENTS Subcellular localization image for HMGCL gene
Compartment Confidence
mitochondrion 5
peroxisome 5
cytosol 1

No data available for Gene Ontology (GO) - Cellular Components for HMGCL Gene

Pathways & Interactions for HMGCL Gene

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

UniProtKB/Swiss-Prot P35914-HMGCL_HUMAN

  • Pathway: Metabolic intermediate metabolism; (S)-3-hydroxy-3-methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA: step 1/1.

Gene Ontology (GO) - Biological Process for HMGCL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001889 liver development IEA --
GO:0006637 acyl-CoA metabolic process IEA --
GO:0007584 response to nutrient IEA --
GO:0042594 response to starvation IEA --
GO:0046950 cellular ketone body metabolic process TAS --
genes like me logo Genes that share ontologies with HMGCL: view

No data available for SIGNOR curated interactions for HMGCL Gene

Drugs & Compounds for HMGCL Gene

(6) Drugs for HMGCL Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
acetic acid Approved Nutra Full agonist, Agonist 97
3-hydroxyglutaric acid Experimental Pharma Target 0
3-Hydroxymethylglutaric acid Experimental Pharma 0
Acetoacetic acid Experimental Pharma 0

(6) Additional Compounds for HMGCL Gene - From: HMDB and Novoseek

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
acetyl-coa
  • Ac-CoA
  • Ac-Coenzyme A
  • Ac-S-CoA
  • Ac-S-Coenzyme A
  • Acetyl coenzyme-A
72-89-9
3-Hydroxy-3-(4-methylpent-3-en-1-yl)glutaryl-CoA
7-Methyl-3-oxo-6-octenoyl-CoA
genes like me logo Genes that share compounds with HMGCL: view

Transcripts for HMGCL Gene

Unigene Clusters for HMGCL Gene

3-hydroxymethyl-3-methylglutaryl-CoA lyase:
Representative Sequences:

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

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b · 12c
SP1: - - - - - - -
SP2: - - - -
SP3: - - - - - - -
SP4: -
SP5: - - - - - -
SP6: - -
SP7:

Relevant External Links for HMGCL Gene

GeneLoc Exon Structure for
HMGCL
ECgene alternative splicing isoforms for
HMGCL

Expression for HMGCL Gene

mRNA expression in normal human tissues for HMGCL Gene

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

This gene is overexpressed in Liver (x8.3).

Protein differential expression in normal tissues from HIPED for HMGCL Gene

This gene is overexpressed in Liver, secretome (16.0) and Liver (8.2).

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



SOURCE GeneReport for Unigene cluster for HMGCL Gene Hs.533444

mRNA Expression by UniProt/SwissProt for HMGCL Gene

P35914-HMGCL_HUMAN
Tissue specificity: Highest expression in liver. Expressed in pancreas, kidey, intestine, testis, fibroblasts and lymphoblasts. Very low expression in brain and skeletal muscle. The relative expression of isoform 2 (at mRNA level) is highest in heart (30%), skeletal muscle (22%), and brain (14%).
genes like me logo Genes that share expression patterns with HMGCL: view

Protein tissue co-expression partners for HMGCL Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for HMGCL Gene

Orthologs for HMGCL Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HMGCL Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia HMGCL 35
  • 88.82 (n)
  • 88.92 (a)
HMGCL 36
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HMGCL 35
  • 88.1 (n)
  • 87.08 (a)
HMGCL 36
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hmgcl 35
  • 84.92 (n)
  • 88 (a)
Hmgcl 16
Hmgcl 36
  • 88 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia HMGCL 35
  • 99.49 (n)
  • 99.69 (a)
HMGCL 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hmgcl 35
  • 84.62 (n)
  • 88.92 (a)
oppossum
(Monodelphis domestica)
Mammalia HMGCL 36
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HMGCL 36
  • 57 (a)
OneToOne
chicken
(Gallus gallus)
Aves HMGCL 35
  • 75.13 (n)
  • 78.68 (a)
HMGCL 36
  • 77 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HMGCL 36
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100494904 35
  • 68.92 (n)
  • 72.67 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 35
hmgcl 35
  • 69.57 (n)
  • 76.13 (a)
hmgcl 36
  • 70 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG10399 37
  • 62 (a)
CG10399 35
  • 60.82 (n)
  • 61.36 (a)
CG10399 36
  • 57 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008717 35
  • 59.66 (n)
  • 65.08 (a)
worm
(Caenorhabditis elegans)
Secernentea Y71G12B.10 37
  • 51 (a)
Y71G12B.10 35
  • 55.77 (n)
  • 53.27 (a)
Y71G12B.10 36
  • 50 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G26800 35
  • 61.43 (n)
  • 64.16 (a)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.372 35
barley
(Hordeum vulgare)
Liliopsida Hv.1703 35
rice
(Oryza sativa)
Liliopsida Os.17868 35
Os01g0269000 35
  • 62.34 (n)
  • 65.53 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.9483 35
corn
(Zea mays)
Liliopsida Zm.6728 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 58 (a)
OneToMany
Species with no ortholog for HMGCL:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • 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)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for HMGCL Gene

ENSEMBL:
Gene Tree for HMGCL (if available)
TreeFam:
Gene Tree for HMGCL (if available)

Paralogs for HMGCL Gene

Paralogs for HMGCL Gene

(2) SIMAP similar genes for HMGCL Gene using alignment to 6 proteins:

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

Variants for HMGCL Gene

Sequence variations from dbSNP and Humsavar for HMGCL Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
VAR_003744 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD)
VAR_003745 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD)
VAR_003746 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD)
VAR_003747 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD)
VAR_003748 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD)

Variation tolerance for HMGCL Gene

Residual Variation Intolerance Score: 22.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.00; 20.65% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HMGCL Gene

HapMap Linkage Disequilibrium report
HMGCL
Human Gene Mutation Database (HGMD)
HMGCL

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for HMGCL Gene

Disorders for HMGCL Gene

MalaCards: The human disease database

(15) MalaCards diseases for HMGCL Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hmg-coa lyase deficiency
  • hmg coa lyase deficiency
3-hydroxy-3-methylglutaryl-coenzyme a lyase deficiency
  • hmg-coa lyase deficiency
organic acidemia
  • organic acid metabolism disorder
reye syndrome
  • reye's syndrome
metabolic acidosis
- elite association - COSMIC cancer census association via MalaCards
Search HMGCL in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HMGCL_HUMAN
  • 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:246450]: An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases. {ECO:0000269 PubMed:11129331, ECO:0000269 PubMed:12746442, ECO:0000269 PubMed:16601870, ECO:0000269 PubMed:17173698, ECO:0000269 PubMed:17459752, ECO:0000269 PubMed:19036343, ECO:0000269 PubMed:19177531, ECO:0000269 PubMed:8798725, ECO:0000269 PubMed:9463337, ECO:0000269 PubMed:9784232}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for HMGCL Gene

defective ketogenesis characterized by recurrent non ketotic hypoglycemia with acidosis,hyperammonemia and hydroxymethylglutaricaciduria

Relevant External Links for HMGCL

Genetic Association Database (GAD)
HMGCL
Human Genome Epidemiology (HuGE) Navigator
HMGCL
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HMGCL
genes like me logo Genes that share disorders with HMGCL: view

Publications for HMGCL Gene

  1. 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency. (PMID: 8440722) Mitchell G.A. … Miziorko H.M. (J. Biol. Chem. 1993) 3 4 23 67
  2. Aberrantly spliced mRNAs of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene with a donor splice-site point mutation produce hereditary HL deficiency. (PMID: 8978493) Buesa C. … Hegardt F.G. (J. Lipid Res. 1996) 2 3 23
  3. 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL): cloning and characterization of a mouse liver HL cDNA and subchromosomal mapping of the human and mouse HL genes. (PMID: 8102917) Wang S. … Miziorko H. (Mamm. Genome 1993) 2 3 23
  4. [Late onset 3-HMG-CoA lyase deficiency: a rare but treatable disorder]. (PMID: 19932602) Pierron S. … Acquaviva C. (Arch Pediatr 2010) 3 23
  5. Ten novel HMGCL mutations in 24 patients of different origin with 3- hydroxy-3-methyl-glutaric aciduria. (PMID: 19177531) Menao S. … Pie J. (Hum. Mutat. 2009) 3 23

Products for HMGCL Gene

Sources for HMGCL Gene

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