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Aliases for HMGCL Gene

Aliases for HMGCL Gene

  • 3-Hydroxymethyl-3-Methylglutaryl-CoA Lyase 2 3
  • 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 64
  • HL 3 4
  • Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Lyase 3
  • Hydroxymethylglutaryl-CoA Lyase, Mitochondrial 3
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase 3

External Ids for HMGCL Gene

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 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

Genomic Location for HMGCL Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for HMGCL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HMGCL Gene

Regulatory Elements 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

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for HMGCL Gene

Protein Domains for HMGCL Gene

UniProtKB/Swiss-Prot:

HMGCL_HUMAN
Family:
  • Belongs to the HMG-CoA lyase family.:
    • P35914
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:0000062 fatty-acyl-CoA binding IEA --
GO:0000287 magnesium ion binding IDA 9200711
GO:0003824 catalytic activity --
GO:0004419 hydroxymethylglutaryl-CoA lyase activity TAS --
GO:0005102 receptor binding IPI 20178365
genes like me logo Genes that share ontologies with HMGCL: view
genes like me logo Genes that share phenotypes with HMGCL: view

Animal Models for HMGCL Gene

MGI Knock Outs for HMGCL:

miRNA for HMGCL Gene

miRTarBase miRNAs that target HMGCL

No data available for Transcription Factor Targeting 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

Gene Ontology (GO) - Cellular Components for HMGCL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA 9869651
GO:0005743 mitochondrial inner membrane IEA --
GO:0005759 mitochondrial matrix TAS --
GO:0005777 peroxisome IDA 9869651
genes like me logo Genes that share ontologies with HMGCL: view

Pathways 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:0006552 leucine catabolic process NAS 9200711
GO:0006637 acyl-CoA metabolic process IEA --
GO:0007005 mitochondrion organization IEA --
GO:0007584 response to nutrient IEA --
genes like me logo Genes that share ontologies with HMGCL: view

Compounds for HMGCL Gene

(4) HMDB Compounds for HMGCL Gene

Compound Synonyms Cas Number PubMed IDs
3-Hydroxy-3-methylglutaryl-CoA
  • (S)-3-hydroxy-3-methylglutaryl-CoA
1553-55-5
3-Hydroxymethylglutaric acid
  • 3-Hydroxy-3-methylglutarate
503-49-1
Acetoacetic acid
  • 3-Ketobutyrate
541-50-4
Acetyl-CoA
  • S-Acetyl coenzyme A
72-89-9

(1) Drugbank Compounds for HMGCL Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
3-hydroxyglutaric acid
638-18-6 target

(6) Novoseek inferred chemical compound relationships for HMGCL Gene

Compound -log(P) Hits PubMed IDs
3-hydroxy-3-methylglutaryl-coa 91.4 20
4-hydroxy-2-oxovalerate 83.8 1
leucine 70.8 11
acetoacetate 65.4 2
acetyl-coa 55.6 2
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 (8.3).

Integrated Proteomics: protein expression 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 expressions with HMGCL: view

Orthologs for HMGCL Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HMGCL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HMGCL 36
  • 99.49 (n)
  • 99.69 (a)
HMGCL 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia HMGCL 36
  • 88.82 (n)
  • 88.92 (a)
HMGCL 37
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HMGCL 36
  • 88.1 (n)
  • 87.08 (a)
HMGCL 37
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hmgcl 36
  • 84.92 (n)
  • 88 (a)
Hmgcl 16
Hmgcl 37
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HMGCL 37
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HMGCL 37
  • 57 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hmgcl 36
  • 84.62 (n)
  • 88.92 (a)
chicken
(Gallus gallus)
Aves HMGCL 36
  • 75.13 (n)
  • 78.68 (a)
HMGCL 37
  • 77 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HMGCL 37
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100494904 36
  • 68.92 (n)
  • 72.67 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 36
hmgcl 36
  • 69.57 (n)
  • 76.13 (a)
hmgcl 37
  • 70 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008717 36
  • 59.66 (n)
  • 65.08 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG10399 36
  • 60.82 (n)
  • 61.36 (a)
CG10399 37
  • 57 (a)
OneToMany
CG10399 38
  • 62 (a)
worm
(Caenorhabditis elegans)
Secernentea Y71G12B.10 36
  • 55.77 (n)
  • 53.27 (a)
Y71G12B.10 37
  • 50 (a)
OneToMany
Y71G12B.10 38
  • 51 (a)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.372 36
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G26800 36
  • 61.43 (n)
  • 64.16 (a)
barley
(Hordeum vulgare)
Liliopsida Hv.1703 36
corn
(Zea mays)
Liliopsida Zm.6728 36
rice
(Oryza sativa)
Liliopsida Os.17868 36
Os01g0269000 36
  • 62.34 (n)
  • 65.53 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.9483 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 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

Selected 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 MAF
rs719399 -- 23,807,972(-) GTACA(A/G)CTCTG intron-variant
rs719400 Benign 23,808,231(-) ATGCT(A/G)TCTGC reference, synonymous-codon
rs974698 -- 23,806,295(+) ctccc(C/T)gcccc intron-variant
rs1018396 -- 23,807,122(+) TGAGC(A/G)TGATC intron-variant
rs2076344 -- 23,817,442(+) TCCCT(A/G)GAGAA intron-variant

Relevant External Links for HMGCL Gene

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

No data available for Structural Variations from Database of Genomic Variants (DGV) for HMGCL Gene

Disorders for HMGCL Gene

(1) OMIM Diseases for HMGCL Gene (613898)

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.

(12) Novoseek inferred disease relationships for HMGCL Gene

Disease -log(P) Hits PubMed IDs
aciduria organic 74.9 2
metabolic acidosis 73.5 2
hyperammonemia 70.3 1
hypoglycemia 68.8 5
reye syndrome 68.4 1

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

Publications for HMGCL Gene

  1. 3-Hydroxy-3-methylglutaryl-CoA lyase is present in mouse and human liver peroxisomes. (PMID: 7527399) Ashmarina L.I. … Mitchell G.A. (J. Biol. Chem. 1994) 3 4 23
  2. 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
  3. 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
  4. 3-hydroxy-3-methylglutaryl CoA lyase (HL): mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients. (PMID: 8617516) Wang S.P. … Mitchell G.A. (Genomics 1996) 3 4 23
  5. 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

Products for HMGCL Gene

  • Addgene plasmids for HMGCL

Sources for HMGCL Gene

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