Protein-coding gene in the species Homo sapiens
HMGCS2 |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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Identifiers |
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Aliases | HMGCS2, 3-hydroxy-3-methylglutaryl-CoA synthase 2 |
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External IDs | OMIM: 600234; MGI: 101939; HomoloGene: 38066; GeneCards: HMGCS2; OMA:HMGCS2 - orthologs |
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Gene location (Human) |
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![Chromosome 1 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Ideogram_human_chromosome_1.svg/300px-Ideogram_human_chromosome_1.svg.png) | Chr. | Chromosome 1 (human)[1] |
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| Band | 1p12 | Start | 119,748,002 bp[1] |
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End | 119,768,905 bp[1] |
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Gene location (Mouse) |
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![Chromosome 3 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/0/08/Ideogram_house_mouse_chromosome_3.svg/260px-Ideogram_house_mouse_chromosome_3.svg.png) | Chr. | Chromosome 3 (mouse)[2] |
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| Band | 3 F2.2|3 42.74 cM | Start | 98,187,751 bp[2] |
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End | 98,218,054 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - right lobe of liver
- mucosa of transverse colon
- jejunal mucosa
- rectum
- mucosa of sigmoid colon
- duodenum
- renal medulla
- human kidney
- thoracic diaphragm
- apex of heart
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| Top expressed in | - left lobe of liver
- lumbar spinal ganglion
- Stroma of ovary
- migratory enteric neural crest cell
- retinal pigment epithelium
- duodenum
- gastrula
- tunica media of zone of aorta
- vestibular sensory epithelium
- sexually immature organism
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| More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | - transferase activity
- catalytic activity
- hydroxymethylglutaryl-CoA synthase activity
| Cellular component | - mitochondrion
- mitochondrial matrix
| Biological process | - steroid metabolic process
- sterol biosynthetic process
- lipid metabolism
- cholesterol metabolic process
- isoprenoid biosynthetic process
- cholesterol biosynthetic process
- metabolism
- steroid biosynthetic process
- ketone body biosynthetic process
- regulation of lipid metabolic process
- acetyl-CoA metabolic process
- farnesyl diphosphate biosynthetic process, mevalonate pathway
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 1: 119.75 – 119.77 Mb | Chr 3: 98.19 – 98.22 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial) is an enzyme in humans that is encoded by the HMGCS2 gene.[5]
The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the second and rate-limiting reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting, by addition of a third acetyl group to acetoacetyl-CoA, producing HMG-CoA.[6]
Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[5]
Clinical significance
Mutations in this gene are associated with mitochondrial HMG-CoA synthase deficiency (also known as HMGCS2D), affecting ketone body synthesis.[7] Affected patients are unable to perform ketogenesis during starvation and times of higher energy need such as fever and vigorous exercise. Commonly found is damage to heart muscles and the brain, along with hypoglycemia (not always present)[8] and elevated blood fatty acid concentration. The mortality rate is 20%.[9] Urine organic acid analysis can be used to detect likely cases, which can be further confirmed using DNA sequencing.[10]
Occurrence
HMGCS2 is not found in cetaceans, elephantids, or Old World fruit bats. Fruit bats are known to be very sensitive to starvation, similar to humans with HMGCS2D. The other two groups seem to have evolved other means of coping with starvation.[11]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000134240 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027875 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)".
- ^ Drabbe S, Pelzer A, Slenter D, Willighagen E (February 2023). "Disorders in ketone body synthesis (Homo sapiens)". Wiki Pathways.
- ^ Aledo R, Mir C, Dalton RN, Turner C, Pié J, Hegardt FG, et al. (February 2006). "Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency". Journal of Inherited Metabolic Disease. 29 (1): 207–211. doi:10.1007/s10545-006-0214-2. PMID 16601895. S2CID 24866271.
- ^ Conlon, TA; Fitzsimons, PE; Borovickova, I; Kirby, F; Murphy, S; Knerr, I; Crushell, E (September 2020). "Hypoglycemia is not a defining feature of metabolic crisis in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: Further evidence of specific biochemical markers which may aid diagnosis". JIMD Reports. 55 (1): 26–31. doi:10.1002/jmd2.12146. PMC 7463059. PMID 32905056.
- ^ 丹, 马; 丹, 俞 (11 November 2018). "线粒体3-羟基3-甲基戊二酰辅酶A合成酶缺乏症1例并文献复习" [Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase deficiency: a case report and literature review]. Chinese Journal of Contemporary Pediatrics (in Chinese). 20 (11): 930–933. doi:10.7499/j.issn.1008-8830.2018.11.010. ISSN 1008-8830. PMC 7389032. PMID 30477625.
- ^ Conlon, TA; Fitzsimons, PE; Borovickova, I; Kirby, F; Murphy, S; Knerr, I; Crushell, E (September 2020). "Hypoglycemia is not a defining feature of metabolic crisis in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: Further evidence of specific biochemical markers which may aid diagnosis". JIMD Reports. 55 (1): 26–31. doi:10.1002/jmd2.12146. PMC 7463059. PMID 32905056.
- ^ Jebb D, Hiller M (October 2018). "Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains". eLife. 7: e38906. doi:10.7554/eLife.38906. PMC 6191284. PMID 30322448.
External links
- Overview of all the structural information available in the PDB for UniProt: P54868 (Human Hydroxymethylglutaryl-CoA synthase, mitochondrial) at the PDBe-KB.
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Portal:
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