HMGCL

Protein identityUniProt · HPA

UniProt accession

P35914

Gene

HMGCL

Ensembl

ENSG00000117305

Chromosome

1

Canonical length

325 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Quaternary structure

Homotetramer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

325 residues, UniProt reviewed canonical sequence.

>P35914|HMGCL
     1  MAAMRKALPR RLVGLASLRA VSTSSMGTLP KRVKIVEVGP RDGLQNEKNI VSTPVKIKLI
    61  DMLSEAGLSV IETTSFVSPK WVPQMGDHTE VLKGIQKFPG INYPVLTPNL KGFEAAVAAG
   121  AKEVVIFGAA SELFTKKNIN CSIEESFQRF DAILKAAQSA NISVRGYVSC ALGCPYEGKI
   181  SPAKVAEVTK KFYSMGCYEI SLGDTIGVGT PGIMKDMLSA VMQEVPLAAL AVHCHDTYGQ
   241  ALANTLMALQ MGVSVVDSSV AGLGGCPYAQ GASGNLATED LVYMLEGLGI HTGVNLQKLL
   301  EAGNFICQAL NRKTSSKVAQ ATCKL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HMGCL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

322 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HMGCL.

Disease | AllUniProt

Conditions HMGCL is implicated in, by any mechanism.

• 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) MIM:246450

Disease | GeneticClinVar

103 pathogenic / likely-pathogenic of 567 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Deficiency of hydroxymethylglutaryl-CoA lyase
• Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
• Inborn genetic diseases
• HMGCL-related disorder
• Ovarian serous cystadenocarcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.11

gnomAD pLI

0

gnomAD missense Z

0.46

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ketone body biosynthetic process
• L-leucine catabolic process
• lipid metabolic process
• mitochondrion organization

Molecular functions

• hydroxymethylglutaryl-CoA lyase activity
• magnesium ion binding
• manganese ion binding
• metal ion binding
• structural molecule activity

Cellular components

• cytosol
• mitochondrial matrix
• mitochondrion
• peroxisomal matrix
• peroxisome
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Pyruvate carboxyltransferase
• Aldolase-type TIM barrel
• HMG-CoA lyase
• HMGL-like
• Hydroxymethylglutaryl-CoA lyase, active site

KeywordsUniProt

• Acetylation
• Disulfide bond
• Lipid metabolism
• Lyase
• Metal-binding
• Mitochondrion
• Peroxisome
• Transit peptide