Sodium- and chloride-dependent glycine transporter 1

Sodium- and chloride-dependent glycine transporter 1, also known as glycine transporter 1, is a protein that in humans is encoded by the SLC6A9 gene which is promising therapeutic target for treatment of diabetes and obesity. [5][6][7][8]

SLC6A9
Identifiers
AliasesSLC6A9, GLYT1, Glycine transporter 1, solute carrier family 6 member 9, GCENSG
External IDsOMIM: 601019; MGI: 95760; HomoloGene: 5050; GeneCards: SLC6A9; OMA:SLC6A9 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_008135
NM_001355175
NM_001369016
NM_001369017

RefSeq (protein)

NP_032161
NP_001342104
NP_001355945
NP_001355946

Location (UCSC)Chr 1: 43.99 – 44.03 MbChr 4: 117.69 – 117.73 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Selective inhibitors

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Elevation of extracellular synaptic glycine concentration by blockade of GlyT1 has been hypothesized to potentiate NMDA receptor function in vivo and to represent a rational approach for the treatment of schizophrenia and cognitive disorders. Several drug candidates have reached clinical trials.[9]

  • ASP2535[10]
  • Bitopertin (RG1678), which has entered phase II trials for the treatment of schizophrenia[11]
  • Iclepertin (BI 425809) by Boehringer Ingelheim which is thought to improve cognitive impairment due to schizophrenia
  • Org 25935 (Sch 900435)
  • PF-03463275 (in phase II trial)
  • Pesampator (PF-04958242) by Pfizer
  • Sarcosine which is thought to improve cognitive impairment due to schizophrenia

Pathological mutations

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Mutations of the gene may cause a severe metabolic disorder discovered in 2016 and called glycine encephalopathy with normal serum glycine (OMIM 617301), also known as GlyT1 encephalopathy.

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196517Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028542Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Sinha, Jitendra Kumar; Durgvanshi, Shantanu; Verma, Manish; Ghosh, Shampa (June 2023). "Investigation of SLC6A9 and SLC5A1 as a promising therapeutic target for obesity and diabetes using in silico characterization, 3D structure prediction and molecular docking analysis". Alzheimer's & Dementia. 19 (S1). doi:10.1002/alz.064229. ISSN 1552-5260.
  6. ^ Kim KM, Kingsmore SF, Han H, Yang-Feng TL, Godinot N, Seldin MF, Caron MG, Giros B (Jun 1994). "Cloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes". Mol Pharmacol. 45 (4): 608–17. PMID 8183239.
  7. ^ Jones EM, Fernald A, Bell GI, Le Beau MM (Nov 1995). "Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization". Cytogenet Cell Genet. 71 (3): 211. doi:10.1159/000134110. PMID 7587377.
  8. ^ "Entrez Gene: SLC6A9 solute carrier family 6 (neurotransmitter transporter, glycine), member 9".
  9. ^ Harvey, Robert J.; Yee, Benjamin K. (31 October 2013). "Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain". Nature Reviews Drug Discovery. 12 (11): 866–85. doi:10.1038/nrd3893. PMID 24172334. S2CID 28022131.
  10. ^ Harada K, Nakato K, Yarimizu J, Yamazaki M, Morita M, Takahashi S, Aota M, Saita K, Doihara H, Sato Y, Yamaji T, Ni K, Matsuoka N (2012). "A novel glycine transporter-1 (GlyT1) inhibitor, ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole), improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease". European Journal of Pharmacology. 685 (1–3): 59–69. doi:10.1016/j.ejphar.2012.04.013. PMID 22542656.
  11. ^ Pinard E, Alanine A, Alberati D, Bender M, Borroni E, Bourdeaux P, Brom V, Burner S, Fischer H, Hainzl D, Halm R, Hauser N, Jolidon S, Lengyel J, Marty HP, Meyer T, Moreau JL, Mory R, Narquizian R, Nettekoven M, Norcross RD, Puellmann B, Schmid P, Schmitt S, Stalder H, Wermuth R, Wettstein JG, Zimmerli D (June 2010). "Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia". J. Med. Chem. 53 (12): 4603–14. doi:10.1021/jm100210p. PMID 20491477.

Further reading

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