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FLASH GENE
Symbol SLC2A9 contributors: mct/npt - updated : 14-12-2013
HGNC name solute carrier family 2 (facilitated glucose transporter), member 9
HGNC id 13446
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal domain having a unique regulatory function and the potential to interact with small negatively charged ions like iodide
  • characteristic 12 transmembrane helices
  • sugar transporter motifs and other signatures of facilitated sugar transporters
  • although it lacks the features of a high-affinity glucose transporter, suggesting alternative substrates
  • HOMOLOGY
    interspecies homolog to murine slc2a9
    intraspecies homolog to GLUT1,GLUT5
    Homologene
    FAMILY
  • major facilitator superfamily
  • sugar transporter family
  • glucose transporter subfamily
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • playing a role in maintaining glucose homeostasis
  • involvement of the protein in uric acid excretion in the kidney
  • a fructose and a urate transporter
  • play a key role in urate reabsorption on both urine and blood sides of the renal proximal tubules
  • directly regulates plasma uric acid (urate) levels by transporting uric acid out of the tubular cell, in a voltage-driven manne (Houlihan 2010)
  • link between cognitive ability in old age, in particular memory performance, to SLC2A9 (Houlihan 2010)
  • SLC2A9 mediated the uptake of adenine in addition to urate, but did not function as a generalized nucleobase transporter
  • play key roles in the regulation of plasma urate levels and are therefore potentially important participants in hyperuricemia and hypouricemia
  • evidence for SLC2A9 and SLC2A12 expression in vascular smooth muscle cells (VSMCs) in conjunction with the previously identified SLC2A1 and SLC2A10
  • is an essential protein that mainly regulates urate/hexose homeostasis in human kidney and liver
  • SLC2A9 transports both urate and fructose, but it interacts with them in different ways
  • is unique in that it transports hexoses as well as the organic anion, urate
  • urate transport in SLC2A9 involves several structural elements rather than just a unique substrate binding pocket
  • is a crucial player in renal handling of urate
  • high&
  • 8209;capacity glucose and urate transporter
    CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS facilitated diffusion transport
    PATHWAY
    metabolism carbohydrate
    signaling
  • TP53-SLC2A9 pathway is a novel antioxidant mechanism that uses uric acid to maintain ROS homeostasis and prevent accumulation of ROS-associated damage that potentially contributes to cancer development
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • functional cooperation of SLC22A12 and SLC22A9 is essential for renal reabsorption of urate, and in the established system influence of drugs on serum urate (SUA) is reflected in the alteration of urate permeability across the renal tubular epithelial cells
  • HNF4A contributes to the transcriptional regulation of SLC2A9
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) RHU2
    Susceptibility
  • to gout
  • to hyperuricemia
  • Variant & Polymorphism SNP , other
  • significant association between the SLC2A9 isoform 2 and urate concentrations and gout
  • genetic variants significantly associated with uric acid levels, association strongly modified by age and sex (Brandstätter 2009)
  • some of SNP in SLC2A9 may increase the risk of hyperuricemia
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    metabolismuric acid 
    can be a promising therapeutic target for hyperuricemia, gout, and related cardiovascular diseases
    ANIMAL & CELL MODELS
  • mice carrying a deletion of Glut9 in the whole body are hyperuricemic and display a severe nephropathy due to intratubular uric acid precipitation
  • Glut9-deficient mice develop impaired enterocyte uric acid transport kinetics, hyperuricaemia, hyperuricosuria, spontaneous hypertension, dyslipidaemia and elevated body fat