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FLASH GENE
Symbol SLC6A9 contributors: mct/npt - updated : 02-06-2015
HGNC name solute carrier family 6 (neurotransmitter transporter, glycine), member 9
HGNC id 11056
DNA
TYPE functioning gene
STRUCTURE 34.98 kb     14 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 - 3206 - 633 - Geerlings (2002)
14 - 3375 - 706 - Geerlings (2002)
13 - 3213 - 652 - Geerlings (2002)
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrainforebraincerebral cortex   Homo sapiens
 brainlimbic systemhippocampus   Rattus norvegicus
Reproductivefemale systemuteruscervix  
 female systembreastmammary gland  
Visualeyeretina  highly
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousastrocyte Rattus norvegicus
Nervousneuron Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 12 transmembrane segments (12TM)
  • C-terminus, which regulates transporter trafficking and cellular surface density, and contains PDZ binding motif responsible for SLC6A9 interaction with trafficking and clustering proteins
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
  • sodium: neurotransmitter symporter (SNF) family
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • being present mainly on the plasma membrane (López-Corcuera 2001)
  • with membrane rafts are co-localized in the membrane, and this influences the rate of glycine transport (Liu 2009)
  • astrocytes express functional SLC6A5, which challenge previous findings that those cells would express only SLC6A9, whereas SLC6A5 was supposed to be restricted to the glycinergic nerve terminals
  • expressed not only at the plasma membrane of glutamatergic neurons, but also at synaptic vesicles
  • is located predominantly on astrocytes
  • basic FUNCTION
  • Na+ (and Cl-) dependent plasma membrane transporter
  • plays a pivotal role in maintaining the glycine level at the glutamatergic synapse
  • may play a role in regulation of glycine levels in NMDA receptor-mediated neurotransmission
  • likely mediating glycine uptake in cortical fiber cells, but not responsible for the accumulation of glycine in the center of the lens
  • most likely mediates glycine transport at the inner blood-retinal barrier and is expected to play an important role in regulating the glycine concentration in the neural retina (Okamoto 2009)
  • regulates both glycinergic and glutamatergic neurotransmission by controlling the reuptake of glycine at synapse (Fernández-Sánchez 2009)
  • plays important role in maintaining accurate glycine concentration in local brain microenvironment
  • glycine transport by SLC6A9 is inhibited by lithium whereas SLC6A5 transport is stimulated, and this effect is more evident at increased glycine concentrations
  • essential role in glycine mediated cytoprotection in intestinal absorptive cells
  • neuronal and glial SLC6A9 may regulate cognitive functions via dissociable mechanisms
  • mainly glial glycine transporter, primarily responsible for the completion of inhibitory neurotransmission
  • SLC6A5, SLC6A9 are the transporters responsible for glycine uptake from the synaptic cleft
  • functional role of SLC6A9 in a subpopulation of glutamatergic vesicles
  • SLC6A5, SLC6A9 are responsible for the termination of glycine-mediated synaptic activity through removal of neurotransmitter from synaptic cleft
  • is essential for the clearance of glycine from the extracellular space and termination of glycinergic neurotransmission
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with HMGN3
  • GSK3B is important for stabilizing and/or controlling the expression of functional SLC6A5, SLC6A9 on the neural cell surface
  • BDNF, via truncated NTRK2, modulates SLC6A9 and SLC6A5 in astrocytes
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SLC6A9D
    Susceptibility
  • to methamphetamine dependence and psychosis
  • to essential hypertension
  • Variant & Polymorphism SNP
  • increasing the risk of methamphetamine dependence and psychosis
  • association between SLC6A9 gene polymorphisms rs2286245 and essential hypertension (Ueno 2009)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyepilepsy 
    SLC6A9 inhibitors constitute a new class of antiictogenic drugs
    ANIMAL & CELL MODELS
  • Slc6a9-null mice die several hours after birth as a result of generalized hypotonia and respiratory failure