hydroxymethylglutaryl-CoA synthase 2 | Lanosterol biosynthesis pathway | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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hydroxymethylglutaryl-CoA synthase 2

Target id: 2432

Nomenclature: hydroxymethylglutaryl-CoA synthase 2

Family: Lanosterol biosynthesis pathway

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 508 1p13-p12 HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 2
Mouse - 508 3 42.74cM Hmgcs2 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2
Rat - 508 2q34 Hmgcs2 3-hydroxy-3-methylglutaryl-CoA synthase 2
Previous and Unofficial Names
mitochondrial HMGCoA synthase | 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
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
EC Number: Acetyl CoA + H2O + acetoacetyl CoA -> (S)-3-hydroxy-3-methylglutaryl-CoA + coenzyme A
Tissue Distribution
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
Colonic epithelium
Species:  Human
Technique:  Northern blot
References:  3
Clinically-Relevant Mutations and Pathophysiology
Disease:  3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency
OMIM: 605911
Orphanet: ORPHA35701
References:  7
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human F174L 520T>C 1
Gene Expression and Pathophysiology
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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