Property Summary

NCBI Gene PubMed Count 40
PubMed Score 83.09
PubTator Score 112.63

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (2)

Disease log2 FC p
psoriasis 1.300 5.7e-04
colon cancer -1.100 3.1e-03

Protein-protein Interaction (5)

Gene RIF (20)

PMID Text
25872961 this is the first study describing HMGCL deficiency caused by uniparental disomy.
24333427 This efficient UPLC-MS/MS assay permits rapid and high sensitive determination of HMGCR enzyme activity, tracing potential alterations in cholesterol biosynthesis.
23465862 in the 2 stop codon mutations c.109G>T and c.504_505delCT studied, the stop codon does not appear to be the cause of aberrant splicing; the mutation c.504_505delCT causes 2 mRNA transcripts with a stop codon that generate two simultaneous nonsense-mediated mRNA decay phenomena
22865860 analysis of HMGCLL1 as an extramitochondrial human 3-hydroxy-3-methylglutaryl-CoA lyase and comparison with MHGCL
21952825 An alternative transcript of HMGCS2 carrying a deletion of exon 4, and two alternative transcripts of HMGCL with deletions of exons 5 and 6, and exons 5, 6 and 7, respectively, were detected.
21514269 levels of enzyme activity do not strongly correlate with formation of inter-subunit adducts by HMGCL mutants. C170S, C266S, and C323S proteins do not form inter-subunit disulfide adducts but such an adduct is restored in the C170S/C174S double mutant.
20877624 Observational study of gene-disease association. (HuGE Navigator)
20558737 Crystal structures of ternary complexes of WT HMGCL with the competitive inhibitor 3-hydroxyglutaryl-CoA and of the catalytically deficient HMGCL R41M mutant with substrate HMG-CoA have been determined to 2.4 and 2.2 A.
19932602 We report on a new case of 3-hydroxy-3-methylglutaric aciduria particular by its late onset in a 3-year-old patient. Molecular investigation identified two new sequence modifications in the HMGCL gene: c.494G>A (p.Arg165Gln) and c.820G>A (p.Gly274Arg).
19177531 Finding that all identified missense mutations cause a >95% decrease in the enzyme activity, indicates that the disease appears only in very severe genotypes.
19036343 The unique HMGCL gene mutations exist in Taiwanese 3-hydroxy-3-methylglutaryl CoA lyase deficiency deficiency patients.
17459752 HMG-CoA located on the surface of the enzyme implicates Asn(311) and Lys(313) in substrate binding by establishing polar contacts with phosphate and ribose groups of adenosine, and Lys(48) by contacting the carboxyl group of the panthotenic acid moiety.
17173698 findings of common mutations in HMGCL have direct implications on rapid molecular diagnosis, prenatal and pre-implantation diagnosis and population based prevention programs directed towards 3HMG in Saudi Arabia.
16330550 Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase
15764642 Observational study of gene-disease association. (HuGE Navigator)
15752612 Exon 2 of HL skipping led to the loss of beta-sheet 1, and the skipping of exons 2 and 3 caused the disappearance of alpha helix 1 and beta-sheets 1 and 2
15164951 Data describe the DNA mutational analysis of 3-hydroxy-3-methylglutaryl-coenzyme A lyase.
15122894 A role is suggested for arginine-41 in deprotonation or enolization of acetyldithio-CoA, implicating this residue in the HMG-CoA cleavage reaction chemistry that leads to acetyl-CoA product formation.
12464283 The peroxisomal enzyme forms a covalently linked dimeric species upon crosslinking with dibromopropanone or o-phenylenedimaleimide . Cysteine-323 is required for intersubunit covalent crosslinking.
11952809 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)

AA Sequence

MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSV      1 - 70
IETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNIN     71 - 140
CSIEESFQRFDAILKAAQSANISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGT    141 - 210
PGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATED    211 - 280
LVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL                             281 - 325
//

Text Mined References (51)

PMID Year Title
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25872961 2015 Application of multiplex ligation-dependent probe amplification, and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.
24333427 2014 Measurement of HMG CoA reductase activity in different human cell lines by ultra-performance liquid chromatography tandem mass spectrometry.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23465862 2013 Analysis of aberrant splicing and nonsense-mediated decay of the stop codon mutations c.109G>T and c.504_505delCT in 7 patients with HMG-CoA lyase deficiency.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22865860 2012 Identification and characterization of an extramitochondrial human 3-hydroxy-3-methylglutaryl-CoA lyase.
22847177 2012 Characterization of a novel HMG-CoA lyase enzyme with a dual location in endoplasmic reticulum and cytosol.
21952825 2012 Characterization of splice variants of the genes encoding human mitochondrial HMG-CoA lyase and HMG-CoA synthase, the main enzymes of the ketogenesis pathway.
21514269 2011 Influence of multiple cysteines on human 3-hydroxy-3-methylglutaryl-CoA lyase activity and formation of inter-subunit adducts.
21269460 2011 Initial characterization of the human central proteome.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20558737 2010 Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes.
20178365 2010 A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities.
19932602 2010 [Late onset 3-HMG-CoA lyase deficiency: a rare but treatable disorder].
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19177531 2009 Ten novel HMGCL mutations in 24 patients of different origin with 3-hydroxy-3-methyl-glutaric aciduria.
19036343 2009 Molecular analysis of Taiwanese patients with 3-hydroxy-3-methylglutaryl CoA lyase deficiency.
17459752 2007 C-terminal end and aminoacid Lys48 in HMG-CoA lyase are involved in substrate binding and enzyme activity.
17173698 2006 Mutations underlying 3-hydroxy-3-methylglutaryl CoA lyase deficiency in the Saudi population.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16601870 2006 A single-residue mutation, G203E, causes 3-hydroxy-3-methylglutaric aciduria by occluding the substrate channel in the 3D structural model of HMG-CoA lyase.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16330550 2006 Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria.
15764642 2005 Additive effects of the PPARgamma, APOE, and FABP-2 genes in increasing daylong triglycerides of normolipidemic women to concentrations comparable to those in men.
15752612 2005 Skipping of exon 2 and exons 2 plus 3 of HMG-CoA lyase (HL) gene produces the loss of beta sheets 1 and 2 in the recently proposed (beta-alpha)8 TIM barrel model of HL.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15164951 2003 Molecular basis of 3-hydroxy-3-methylglutaric aciduria.
15122894 2004 Evaluation of 3-hydroxy-3-methylglutaryl-coenzyme A lyase arginine-41 as a catalytic residue: use of acetyldithio-coenzyme A to monitor product enolization.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12874287 2003 Investigation of conserved acidic residues in 3-hydroxy-3-methylglutaryl-CoA lyase: implications for human disease and for functional roles in a family of related proteins.
12746442 2003 Structural (betaalpha)8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12464283 2002 Investigation of the oligomeric status of the peroxisomal isoform of human 3-hydroxy-3-methylglutaryl-CoA lyase.
11952809 2002 Relationship of genetic variation in genes encoding apolipoprotein A-IV, scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with cholesterol metabolism and the response to plant stanol ester consumption.
11129331 2000 Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency.
9869651 1999 3-Hydroxy-3-methylglutaryl coenzyme A lyase: targeting and processing in peroxisomes and mitochondria.
9784232 1998 Two missense point mutations in different alleles in the 3-hydroxy-3-methylglutaryl coenzyme A lyase gene produce 3-hydroxy-3-methylglutaric aciduria in a French patient.
9463337 1998 HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q.
9200711 1997 Evidence supporting a role for histidine-235 in cation binding to human 3-hydroxy-3-methyglutaryl-CoA lyase.
8978493 1996 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.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8798725 1996 Modeling of a mutation responsible for human 3-hydroxy-3-methylglutaryl-CoA lyase deficiency implicates histidine 233 as an active site residue.
8670134 1996 Characterization of the hydroxymethylglutaryl-CoA lyase precursor, a protein targeted to peroxisomes and mitochondria.
8617516 1996 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.
8566388 1995 Ketogenic flux from lipids and leucine, assessment in 3-hydroxy-3-methylglutaryl CoA lyase deficiency.
8440722 1993 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.
8102917 1993 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.
8027038 1994 3-Hydroxy-3-methylglutaryl-CoA lyase: expression and isolation of the recombinant human enzyme and investigation of a mechanism for regulation of enzyme activity.
7527399 1994 3-Hydroxy-3-methylglutaryl-CoA lyase is present in mouse and human liver peroxisomes.
2116546 1990 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: biochemical studies and family investigation of four generations.