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hydroxymethylglutaryl-CoA synthase 2

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Target not currently curated in GtoImmuPdb

Target id: 2432

Nomenclature: hydroxymethylglutaryl-CoA synthase 2

Family: Lanosterol biosynthesis pathway

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 508 1p12 HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 2
Mouse - 508 3 42.74 cM Hmgcs2 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2
Rat - 508 2q34 Hmgcs2 3-hydroxy-3-methylglutaryl-CoA synthase 2
Previous and Unofficial Names Click here for help
mitochondrial HMGCoA synthase | 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (HMGCS2)
Resolution:  1.7Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: Acetyl CoA + H2O + acetoacetyl CoA -> (S)-3-hydroxy-3-methylglutaryl-CoA + coenzyme A
Tissue Distribution Click here for help
Colonic epithelium
Species:  Human
Technique:  Northern blot
References:  3
Liver, colon (high), testis, kidney, heart, skeletal muscles (low), pancreas (very low expression detected)
Species:  Human
Technique:  RNA blot analysis
References:  4
Liver (high expression), kidney, pancreas, testis (medium), heart and skeletal muscle (low expression)
Species:  Human
Technique:  Quantitative PCR
References:  5
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency
OMIM: 605911
Orphanet: ORPHA35701
References:  7
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human F174L 520T>C 1
Gene Expression and Pathophysiology Click here for help
HMGCS2 is downregulated in colon cancer
Tissue or cell type:  Colonic epithelium
Pathophysiology:  Colon cancer
Species:  Human
Technique:  Northern blot
References:  3
General Comments
HMGCoA synthase is found in cytosolic (HMGCoA synthase 1) and mitochondrial (HMGCoA synthase 2) versions; the former associated with synthesis and the latter with ketogenesis.


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1. Bouchard L, Robert MF, Vinarov D, Stanley CA, Thompson GN, Morris A, Leonard JV, Quant P, Hsu BY, Boneh A et al.. (2001) Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients. Pediatr Res, 49 (3): 326-31. [PMID:11228257]

2. Boukaftane Y, Mitchell GA. (1997) Cloning and characterization of the human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase gene. Gene, 195 (2): 121-6. [PMID:9305755]

3. Camarero N, Mascaró C, Mayordomo C, Vilardell F, Haro D, Marrero PF. (2006) Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer. Mol Cancer Res, 4 (9): 645-53. [PMID:16940161]

4. Mascaró C, Buesa C, Ortiz JA, Haro D, Hegardt FG. (1995) Molecular cloning and tissue expression of human mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. Arch Biochem Biophys, 317 (2): 385-90. [PMID:7893153]

5. Puisac B, Ramos M, Arnedo M, Menao S, Gil-Rodríguez MC, Teresa-Rodrigo ME, Pié A, de Karam JC, Wesselink JJ, Giménez I et al.. (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. Mol Biol Rep, 39 (4): 4777-85. [PMID:21952825]

6. Shafqat N, Turnbull A, Zschocke J, Oppermann U, Yue WW. (2010) Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. J Mol Biol, 398 (4): 497-506. [PMID:20346956]

7. Thompson GN, Hsu BY, Pitt JJ, Treacy E, Stanley CA. (1997) Fasting hypoketotic coma in a child with deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. N Engl J Med, 337 (17): 1203-7. [PMID:9337379]


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