Sodium/glucose cotransporter 2

SLC5A2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	7VSI, 7YNK, 7YNJ
Identifiers
Aliases	SLC5A2, SGLT2, solute carrier family 5 member 2
External IDs	OMIM: 182381; MGI: 2181411; HomoloGene: 2289; GeneCards: SLC5A2; OMA:SLC5A2 - orthologs
Gene location (Human)
Chr.	Chromosome 16 (human)
End	31,490,860 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	127,871,602 bp
RNA expression pattern
	Top expressed in
	kidney tubule; ; kidney; ; glomerulus; ; metanephric glomerulus; ; bone marrow cells; ; striated muscle tissue; ; skeletal muscle tissue; ; stromal cell of endometrium; ; renal medulla; ; thymus;
	Top expressed in
	kidney; ; molar; ; mucous cell of stomach; ; supraoptic nucleus; ; ventromedial nucleus; ; crypt of lieberkuhn of small intestine; ; primary motor cortex; ; globus pallidus; ; masseter muscle; ; lateral hypothalamus;
	More reference expression data
	n/a
Gene ontology
Molecular function	low-affinity glucose:sodium symporter activity; symporter activity; transporter activity; glucose:sodium symporter activity; transmembrane transporter activity;
Cellular component	integral component of membrane; plasma membrane; extracellular exosome; membrane; integral component of plasma membrane;
Biological process	carbohydrate transport; ion transport; glucose transmembrane transport; sodium ion transport; transmembrane transport; hexose transmembrane transport; transport; carbohydrate metabolic process;
	Sources:Amigo / QuickGO
Orthologs
	6524
	246787
	ENSG00000140675
	ENSMUSG00000030781
	P31639
	Q923I7
	NM_003041
	NM_133254
	NP_003032
	NP_573517
	Wikidata
View/Edit Human	View/Edit Mouse

The sodium/glucose cotransporter 2 (SGLT2) is a protein that in humans is encoded by the SLC5A2 (solute carrier family 5 (sodium/glucose cotransporter)) gene.^[5]

Function

SGLT2 is a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. SGLT2 is the major cotransporter involved in glucose reabsorption in the kidney.^[6]

SGLT2 inhibitors for diabetes

SGLT2 inhibitors are called gliflozins and are listed in the article gliflozins. They lead to a reduction in blood glucose levels. Therefore, SGLT2 inhibitors have potential use in the treatment of type II diabetes. Gliflozins enhance glycemic control as well as reduce body weight and systolic and diastolic blood pressure.^[7] The gliflozins canagliflozin, dapagliflozin, and empagliflozin may lead to euglycemic ketoacidosis.^[8] Other side effects of gliflozins include increased risk of (generally mild) urinary tract infections, candidal vulvovaginitis.^[9]

Clinical significance

Mutations in this gene are also associated with renal glucosuria.^[10]

Model organisms

*Slc5a2* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Abnormal^[11]
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Salmonella infection	Normal^[12]
Citrobacter infection	Normal^[13]
All tests and analysis from^[14]^[15]

Model organisms have been used in the study of SLC5A2 function. A conditional knockout mouse line, called Slc5a2^{tm1a(KOMP)Wtsi}^[16]^[17] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[18]^[19]^[20]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[14]^[21] Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males displayed increased drinking behaviour.^[14]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000140675 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030781 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Wells RG, Mohandas TK, Hediger MA (Sep 1993). "Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere". Genomics. 17 (3): 787–9. doi:10.1006/geno.1993.1411. PMID 8244402.
^ "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)".
^ Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD (2014). "Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin". Nutrition & Diabetes. 4 (11): e143. doi:10.1038/nutd.2014.40. PMID 25365416.
^ "FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood". Food and Drug Administration, USA. 2015-05-15.
^ "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.
^ Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J (Mar 2006). "Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting". Kidney International. 69 (5): 852–5. doi:10.1038/sj.ki.5000194. PMID 16518345.
^ "Indirect calorimetry data for Slc5a2". Wellcome Trust Sanger Institute.
^ "Salmonella infection data for Slc5a2". Wellcome Trust Sanger Institute.
^ "Citrobacter infection data for Slc5a2". Wellcome Trust Sanger Institute.
^ ^a ^b ^c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
^ "International Knockout Mouse Consortium".
^ "Mouse Genome Informatics".
^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.{{cite journal}}: CS1 maint: unflagged free DOI (link)

van den Heuvel LP, Assink K, Willemsen M, Monnens L (Dec 2002). "Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2)". Human Genetics. 111 (6): 544–7. doi:10.1007/s00439-002-0820-5. PMID 12436245.
Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JH, Kemper M, Li Volti S, Neuhaus T, Skovby F, Swift PG, Schaub J, Klaerke D (Nov 2003). "Molecular analysis of the SGLT2 gene in patients with renal glucosuria". Journal of the American Society of Nephrology. 14 (11): 2873–82. doi:10.1097/01.asn.0000092790.89332.d2. PMID 14569097.
Wells RG, Pajor AM, Kanai Y, Turk E, Wright EM, Hediger MA (Sep 1992). "Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter". The American Journal of Physiology. 263 (3 Pt 2): F459-65. PMID 1415574.
Calado J, Sznajer Y, Metzger D, Rita A, Hogan MC, Kattamis A, Scharf M, Tasic V, Greil J, Brinkert F, Kemper MJ, Santer R (Dec 2008). "Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion". Nephrology, Dialysis, Transplantation. 23 (12): 3874–9. doi:10.1093/ndt/gfn386. PMID 18622023.
Calado J, Soto K, Clemente C, Correia P, Rueff J (Feb 2004). "Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria". Human Genetics. 114 (3): 314–6. doi:10.1007/s00439-003-1054-x. PMID 14614622.
Magen D, Sprecher E, Zelikovic I, Skorecki K (Jan 2005). "A novel missense mutation in SLC5A2 encoding SGLT2 underlies autosomal-recessive renal glucosuria and aminoaciduria". Kidney International. 67 (1): 34–41. doi:10.1111/j.1523-1755.2005.00053.x. PMID 15610225.
Castaneda F, Burse A, Boland W, Kinne RK (2007). "Thioglycosides as inhibitors of hSGLT1 and hSGLT2: potential therapeutic agents for the control of hyperglycemia in diabetes". International Journal of Medical Sciences. 4 (3): 131–9. doi:10.7150/ijms.4.131. PMC 1868657. PMID 17505558.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000140675 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030781 – 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.

[pmid8244402-5] Wells RG, Mohandas TK, Hediger MA (Sep 1993). "Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere". Genomics. 17 (3): 787–9. doi:10.1006/geno.1993.1411. PMID 8244402.

[entrez-6] "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)".

[HaasEckstein2014-7] Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD (2014). "Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin". Nutrition & Diabetes. 4 (11): e143. doi:10.1038/nutd.2014.40. PMID 25365416.

[8] "FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood". Food and Drug Administration, USA. 2015-05-15.

[9] "SGLT2 Inhibitors (Gliflozins)". Diabetes.co.uk. Retrieved 2015-05-19.

[pmid16518345-10] Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J (Mar 2006). "Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting". Kidney International. 69 (5): 852–5. doi:10.1038/sj.ki.5000194. PMID 16518345.

[Indirect_calorimetry-11] "Indirect calorimetry data for Slc5a2". Wellcome Trust Sanger Institute.

[''Salmonella''_infection-12] "Salmonella infection data for Slc5a2". Wellcome Trust Sanger Institute.

[''Citrobacter''_infection-13] "Citrobacter infection data for Slc5a2". Wellcome Trust Sanger Institute.

[mgp_reference-14] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.

[15] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-16] "International Knockout Mouse Consortium".

[mgi_allele_ref-17] "Mouse Genome Informatics".

[pmid21677750-18] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-19] Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-20] Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.

[pmid21722353-21] van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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