• Gene id: 3155

Gene Summary

• Gene Symbol: HMGCL   Gene   UCSC   Ensembl
• Aliases: HL
• Gene name: 3-hydroxy-3-methylglutaryl-CoA lyase
• Alternate names: hydroxymethylglutaryl-CoA lyase, mitochondrial, 3-hydroxy-3-methylglutarate-CoA lyase, 3-hydroxymethyl-3-methylglutaryl-CoA lyase, 3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase, HMG-CoA lyase, hydroxymethylglutaricaciduria, mitochondrial 3-hydroxy-3-methylg,
• Gene location: 1p36.11 (23825458: 23801876)     Exons: 9     NC_000001.11
• Gene summary(Entrez): 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
• OMIM: 614062

Protein Summary

• Protein general information: P35914  
  • Name: Hydroxymethylglutaryl CoA lyase, mitochondrial (HL) (HMG CoA lyase) (EC 4.1.3.4) (3 hydroxy 3 methylglutarate CoA lyase)
  • Length: 325  
  • Mass: 34360
  • Tissue specificity: Highest expression in liver. Expressed in pancreas, kidney, 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
• Sequence:

  MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTS
  FVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNINCSIEESFQRF
  DAILKAAQSANISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEV
  PLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLL
  EAGNFICQALNRKTSSKVAQATCKL

• Structural information:
  • Protein Domains: (33..30-)
    (/note="Pyruvate-carboxyltransferase)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU01151"-)
  • Interpro: IPR013785  IPR000138  IPR000891  
  • Prosite: PS01062 PS50991
  • PDB: 2CW6 3MP3 3MP4 3MP5
  • PDBsum: 2CW6 3MP3 3MP4 3MP5
  • STRING: ENSP00000363614
• Other Databases: GeneCards:  HMGCL  Malacards:  HMGCL

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0046951	ketone body biosynthetic process	IBA	biological process
GO:0006552	leucine catabolic process	IBA	biological process
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IBA	molecular function
GO:0006629	lipid metabolic process	IBA	biological process
GO:0005739	mitochondrion	IBA	cellular component
GO:0046951	ketone body biosynthetic process	IDA	biological process
GO:0046951	ketone body biosynthetic process	IDA	biological process
GO:0046872	metal ion binding	IDA	molecular function
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IDA	molecular function
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IDA	molecular function
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IEA	molecular function
GO:0003824	catalytic activity	IEA	molecular function
GO:0046872	metal ion binding	IEA	molecular function
GO:0016829	lyase activity	IEA	molecular function
GO:0005777	peroxisome	IEA	cellular component
GO:0005739	mitochondrion	IEA	cellular component
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IEA	molecular function
GO:0005759	mitochondrial matrix	TAS	cellular component
GO:0005782	peroxisomal matrix	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0006625	protein targeting to peroxisome	TAS	biological process
GO:0046951	ketone body biosynthetic process	TAS	biological process
GO:0005739	mitochondrion	IEA	cellular component
GO:0070542	response to fatty acid	IEA	biological process
GO:0006637	acyl-CoA metabolic process	IEA	biological process
GO:0005739	mitochondrion	IEA	cellular component
GO:0001889	liver development	IEA	biological process
GO:0007005	mitochondrion organization	IEA	biological process
GO:0046951	ketone body biosynthetic process	IEA	biological process
GO:0042594	response to starvation	IEA	biological process
GO:0031406	carboxylic acid binding	IEA	molecular function
GO:0007584	response to nutrient	IEA	biological process
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IEA	molecular function
GO:0000062	fatty-acyl-CoA binding	IEA	molecular function
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IDA	molecular function
GO:0006552	leucine catabolic process	TAS	biological process
GO:0006629	lipid metabolic process	IDA	biological process
GO:0005759	mitochondrial matrix	IEA	cellular component
GO:0005777	peroxisome	IEA	cellular component
GO:0032991	protein-containing complex	IDA	cellular component
GO:0005198	structural molecule activity	IDA	molecular function
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IDA	molecular function
GO:0005777	peroxisome	IDA	cellular component
GO:0030145	manganese ion binding	IDA	molecular function
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IDA	molecular function
GO:0000287	magnesium ion binding	IDA	molecular function
GO:0005777	peroxisome	IDA	cellular component
GO:0005739	mitochondrion	IDA	cellular component
GO:0046951	ketone body biosynthetic process	IDA	biological process
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IDA	molecular function
GO:0004419	hydroxymethylglutaryl-CoA lyase activity	IDA	molecular function
GO:0006552	leucine catabolic process	NAS	biological process
GO:0005759	mitochondrial matrix	NAS	cellular component

KEGG pathways

Pathway id	Pathway name
hsa01100	Metabolic pathways
hsa04146	Peroxisome
hsa00280	Valine, leucine and isoleucine degradation
hsa00650	Butanoate metabolism
hsa00072	Synthesis and degradation of ketone bodies

Diseases

Associated diseases	References
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency	KEGG:H00179
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency	KEGG:H00179
Amino acid metabolic disorder	PMID:8440722
Aberrant CpGs in Low Motility Sperm	MIK: 21674046
Spermatogenic defects	MIK: 31037746

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
21674046	Aberrant CpGs in Low Motility Sperm			18	Male infertility	GSE26881
31037746	Spermatogenic defects			28 men with azoospermia	Male infertility	Microarray