View source for Biology:Sodium- and chloride-dependent glycine transporter 1

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Sodium- and chloride-dependent glycine transporter 1''', also known as '''glycine transporter 1''', is a [[Biology:Protein|protein]] that in humans is encoded by the ''SLC6A9'' [[Biology:Gene|gene]] which is promising therapeutic target for treatment of diabetes and obesity. <ref>{{Cite journal |last1=Sinha |first1=Jitendra Kumar |last2=Durgvanshi |first2=Shantanu |last3=Verma |first3=Manish |last4=Ghosh |first4=Shampa |date=June 2023 |title=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 |journal=Alzheimer's & Dementia |language=en |volume=19 |issue=S1 |doi=10.1002/alz.064229 |issn=1552-5260|doi-access=free }}</ref><ref name="pmid8183239">{{cite journal |vauthors=Kim KM, Kingsmore SF, Han H, Yang-Feng TL, Godinot N, Seldin MF, Caron MG, Giros B | title = 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 | journal = Mol Pharmacol | volume = 45 | issue = 4 | pages = 608–17 |date=Jun 1994 | pmid = 8183239 }}</ref><ref name="pmid7587377">{{cite journal |vauthors=Jones EM, Fernald A, Bell GI, Le Beau MM | title = Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization | journal = Cytogenet Cell Genet | volume = 71 | issue = 3 | pages = 211 |date=Nov 1995 | pmid = 7587377 | doi = 10.1159/000134110}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC6A9 solute carrier family 6 (neurotransmitter transporter, glycine), member 9| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6536}}</ref>

==Selective inhibitors==
Elevation of extracellular synaptic [[Chemistry:Glycine|glycine]] concentration by blockade of GlyT1 has been hypothesized to potentiate [[Biology:NMDA receptor|NMDA receptor]] function in vivo and to represent a rational approach for the treatment of [[Medicine:Schizophrenia|schizophrenia]] and cognitive disorders. Several drug candidates have reached clinical trials.<ref>{{Cite journal|title = Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain|date = 31 October 2013|journal = Nature Reviews Drug Discovery|doi = 10.1038/nrd3893|pmid = 24172334|volume=12|issue = 11|pages=866–85|last1 = Harvey|first1 = Robert J.|last2 = Yee|first2 = Benjamin K.|s2cid = 28022131}}</ref>
* ASP2535<ref>{{cite journal |vauthors=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 | year = 2012 | title = 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 | journal = European Journal of Pharmacology | volume =  685| issue = 1–3| pages =  59–69| doi = 10.1016/j.ejphar.2012.04.013 | pmid = 22542656 }}</ref>
* [[Chemistry:Bitopertin|Bitopertin]] (RG1678), which has entered [[Engineering:Clinical trial#Phase II|phase II]] trials for the treatment of schizophrenia<ref name="pmid20491477">{{cite journal |vauthors=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 | title = 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 | journal = J. Med. Chem. | volume = 53 | issue = 12 | pages = 4603–14 |date=June 2010 | pmid = 20491477 | doi = 10.1021/jm100210p }}</ref>
* Iclepertin ([[Chemistry:BI 425809|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)
* [[Chemistry:Pesampator|Pesampator]] (PF-04958242) by Pfizer
* [[Chemistry:Sarcosine|Sarcosine]] which is thought to improve cognitive impairment due to schizophrenia

== Pathological mutations==
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==
* Sodium:neurotransmitter symporter
* [[Biology:Solute carrier family|Solute carrier family]]

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
*{{cite journal |vauthors=Olivares L, Aragón C, Giménez C, Zafra F |title=The role of N-glycosylation in the targeting and activity of the GLYT1 glycine transporter |journal=J. Biol. Chem. |volume=270 |issue= 16 |pages= 9437–42 |year= 1995 |pmid= 7721869 |doi=10.1074/jbc.270.16.9437 |doi-access=free }}
*{{cite journal |vauthors=Borowsky B, Mezey E, Hoffman BJ |title=Two glycine transporter variants with distinct localization in the CNS and peripheral tissues are encoded by a common gene |journal=Neuron |volume=10 |issue= 5 |pages= 851–63 |year= 1993 |pmid= 8494645 |doi=10.1016/0896-6273(93)90201-2 |s2cid=24224402 }}
*{{cite journal  |vauthors=Evans J, Herdon H, Cairns W, etal |title=Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter |journal=FEBS Lett. |volume=463 |issue= 3 |pages= 301–6 |year= 2000 |pmid= 10606742 |doi=10.1016/S0014-5793(99)01636-1 |s2cid=21445629 |doi-access= }}
*{{cite journal |vauthors=Hanley JG, Jones EM, Moss SJ |title=GABA receptor rho1 subunit interacts with a novel splice variant of the glycine transporter, GLYT-1 |journal=J. Biol. Chem. |volume=275 |issue= 2 |pages= 840–6 |year= 2000 |pmid= 10625616 |doi=10.1074/jbc.275.2.840 |doi-access=free }}
*{{cite journal |vauthors=Geerlings A, López-Corcuera B, Aragón C |title=Characterization of the interactions between the glycine transporters GLYT1 and GLYT2 and the SNARE protein syntaxin 1A |journal=FEBS Lett. |volume=470 |issue= 1 |pages= 51–4 |year= 2000 |pmid= 10722844 |doi=10.1016/S0014-5793(00)01297-7 |s2cid=46670631 }}
*{{cite journal  |vauthors=Christie GR, Ford D, Howard A, etal |title=Glycine supply to human enterocytes mediated by high-affinity basolateral GLYT1 |journal=Gastroenterology |volume=120 |issue= 2 |pages= 439–48 |year= 2001 |pmid= 11159884 |doi=10.1053/gast.2001.21207 |doi-access=free }}
*{{cite journal |vauthors=Reye P, Penfold P, Pow DV |title=Glyt-1 expression in cultured human Müller cells and intact retinae |journal=Glia |volume=34 |issue= 4 |pages= 311–5 |year= 2001 |pmid= 11360303 |doi=10.1002/glia.1064 |s2cid=39431701 }}
*{{cite journal  |vauthors=Geerlings A, Núñez E, Rodenstein L, etal |title=Glycine transporter isoforms show differential subcellular localization in PC12 cells |journal=J. Neurochem. |volume=82 |issue= 1 |pages= 58–65 |year= 2002 |pmid= 12091465 |doi=10.1046/j.1471-4159.2002.00930.x |doi-access=free }}
*{{cite journal  |vauthors=Brandenberger R, Wei H, Zhang S, etal |title=Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation |journal=Nat. Biotechnol. |volume=22 |issue= 6 |pages= 707–16 |year= 2005 |pmid= 15146197 |doi= 10.1038/nbt971 |s2cid=27764390 }}
*{{cite journal |vauthors=Antonov SM, Brovtsyna NB, Mironova EV |title=The mechanism of allosteric interaction of cytoplasmic and extracellular Cl<sup>−</sup> in the glial glycine transporter (hGlyTlb) |journal=Dokl. Biol. Sci. |volume=402 |issue= 1–6|pages= 163–6 |year= 2005 |pmid= 16121932 |doi=10.1007/s10630-005-0076-z |s2cid=19628294 }}
{{refend}}

{{Membrane transport proteins}}
{{Glycinergics}}
{{Glutamatergics}}

[[Category:Solute carrier family]]



{{Sourceattribution|Sodium- and chloride-dependent glycine transporter 1}}