Sodium- and chloride-dependent glycine transporter 1

SLC6A9
Identifiers
Aliases	SLC6A9 , GLYT1, Glycine transporter 1, solute carrier family 6 member 9, GCENSG
External IDs	OMIM: 601019 MGI: 95760 HomoloGene: 5050 GeneCards: SLC6A9
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p34.1 Start 43,991,500 bp [1] End 44,031,467 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4 D1|4 53.62 cM Start 117,691,703 bp [2] End 117,732,395 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of abdomen right adrenal gland stromal cell of endometrium left adrenal gland hypothalamus upper lobe of left lung right uterine tube substantia nigra internal globus pallidus vagina Top expressed in secondary oocyte retinal pigment epithelium medulla oblongata dorsal tegmental nucleus pontine nuclei medial vestibular nucleus ciliary body globus pallidus superior colliculus cumulus cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function neurotransmitter:sodium symporter activity amino acid:sodium symporter activity glycine transmembrane transporter activity symporter activity glycine:sodium symporter activity transporter activity Cellular component integral component of membrane plasma membrane membrane presynapse integral component of plasma membrane postsynaptic density integral component of synaptic vesicle membrane asymmetric synapse hippocampal mossy fiber to CA3 synapse parallel fiber to Purkinje cell synapse integral component of postsynaptic membrane integral component of presynaptic membrane Biological process amino acid transmembrane transport neurotransmitter transport amino acid transport glycine secretion, neurotransmission glycine transport organic acid transmembrane transport transmembrane transport regulation of synaptic transmission, glycinergic Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6536 14664 Ensembl ENSG00000196517 ENSMUSG00000028542 UniProt P48067 P28571 RefSeq (mRNA) NM_001024845 NM_001261380 NM_006934 NM_201649 NM_001328626 NM_001328627 NM_001328628 NM_001328629 NM_001328630 NM_008135 NM_001355175 NM_001369016 NM_001369017 RefSeq (protein) NP_001020016 NP_001248309 NP_001315555 NP_001315556 NP_001315557 NP_001315558 NP_001315559 NP_008865 NP_964012 NP_032161 NP_001342104 NP_001355945 NP_001355946 Location (UCSC) Chr 1: 43.99 – 44.03 Mb Chr 4: 117.69 – 117.73 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]}

Selective inhibitors

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

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
• Solute carrier family

References

1. GRCh38: Ensembl release 89: ENSG00000196517 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028542 - Ensembl, 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

• Olivares L, Aragón C, Giménez C, Zafra F (1995). "The role of N-glycosylation in the targeting and activity of the GLYT1 glycine transporter". J. Biol. Chem. 270 (16): 9437–42. doi: 10.1074/jbc.270.16.9437 . PMID   7721869.
• Borowsky B, Mezey E, Hoffman BJ (1993). "Two glycine transporter variants with distinct localization in the CNS and peripheral tissues are encoded by a common gene". Neuron. 10 (5): 851–63. doi:10.1016/0896-6273(93)90201-2. PMID   8494645. S2CID   24224402.
• Evans J, Herdon H, Cairns W, et al. (2000). "Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter". FEBS Lett. 463 (3): 301–6. doi:10.1016/S0014-5793(99)01636-1. PMID   10606742. S2CID   21445629.
• Hanley JG, Jones EM, Moss SJ (2000). "GABA receptor rho1 subunit interacts with a novel splice variant of the glycine transporter, GLYT-1". J. Biol. Chem. 275 (2): 840–6. doi: 10.1074/jbc.275.2.840 . PMID   10625616.
• Geerlings A, López-Corcuera B, Aragón C (2000). "Characterization of the interactions between the glycine transporters GLYT1 and GLYT2 and the SNARE protein syntaxin 1A". FEBS Lett. 470 (1): 51–4. doi:10.1016/S0014-5793(00)01297-7. PMID   10722844. S2CID   46670631.
• Christie GR, Ford D, Howard A, et al. (2001). "Glycine supply to human enterocytes mediated by high-affinity basolateral GLYT1". Gastroenterology. 120 (2): 439–48. doi: 10.1053/gast.2001.21207 . PMID   11159884.
• Reye P, Penfold P, Pow DV (2001). "Glyt-1 expression in cultured human Müller cells and intact retinae". Glia. 34 (4): 311–5. doi:10.1002/glia.1064. PMID   11360303. S2CID   39431701.
• Geerlings A, Núñez E, Rodenstein L, et al. (2002). "Glycine transporter isoforms show differential subcellular localization in PC12 cells". J. Neurochem. 82 (1): 58–65. doi: 10.1046/j.1471-4159.2002.00930.x . PMID   12091465.
• Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID   15146197. S2CID   27764390.
• Antonov SM, Brovtsyna NB, Mironova EV (2005). "The mechanism of allosteric interaction of cytoplasmic and extracellular Cl⁻ in the glial glycine transporter (hGlyTlb)". Dokl. Biol. Sci. 402 (1–6): 163–6. doi:10.1007/s10630-005-0076-z. PMID   16121932. S2CID   19628294.