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Mitochondrial disease

Gene: HMGCL

Green List (high evidence)

HMGCL (3-hydroxymethyl-3-methylglutaryl-CoA lyase)
EnsemblGeneIds (GRCh38): ENSG00000117305
EnsemblGeneIds (GRCh37): ENSG00000117305
OMIM: 613898, Gene2Phenotype
HMGCL is in 13 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

3-Hydroxy-3-methylglutaryl coenzyme A lyase catalyzes the cleavage of HMG-CoA to acetoacetic acid and acetyl-CoA, the last step of both ketogenesis and leucine catabolism. It is located in both the mitochondrial matrix and the peroxisomes. The disorder causes metabolic acidosis without ketonuria, hypoglycaemia, and a characteristic pattern of elevated urinary organic acid metabolites, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonaemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting. Well established gene-disease association. Large gene deletions reported.
Created: 3 Jan 2021, 11:30 p.m. | Last Modified: 3 Jan 2021, 11:30 p.m.
Panel Version: 0.5896

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency, MIM# 246450

Publications

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder due to a deficiency of the 3-hydroxy-3-methylglutarylCoA lyase (HMG-CoA lyase), a mitochondrial enzyme involved in ketogenesis and in the final step of l-leucine catabolism. A defect in the substrate-generating upstream reactions of OXPHOS. >3 cases reported.
Sources: NHS GMS, Literature
Created: 21 Mar 2020, 5:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency MIM#246450

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review Green
  • Literature
  • NHS GMS
  • Victorian Clinical Genetics Services
Phenotypes
  • HMG-CoA lyase deficiency MIM#246450
Tags
treatable
OMIM
613898
Clinvar variants
Variants in HMGCL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

26 Sep 2022, Gel status: 3

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag treatable tag was added to gene: HMGCL.

21 Mar 2020, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: hmgcl has been classified as Green List (High Evidence).

21 Mar 2020, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: hmgcl has been classified as Green List (High Evidence).

21 Mar 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: HMGCL was added gene: HMGCL was added to Mitochondrial disease. Sources: NHS GMS,Literature Mode of inheritance for gene: HMGCL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HMGCL were set to 25778941; 11129331; 19036343 Phenotypes for gene: HMGCL were set to HMG-CoA lyase deficiency MIM#246450 Review for gene: HMGCL was set to GREEN