Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTP362L)

• DTT Name: Solute carrier family 12 member 3 (SLC12A3)
• Synonyms: Thiazide-sensitive sodium-chloride cotransporter; Thiazide-sensitive Na-Cl cotransporter; SLC12A3; Na-Cl symporter
• Gene Name: SLC12A3
• DTT Type: Successful target; [1]
• BioChemical Class: Cation-chloride cotransporter
• UniProt ID: S12A3_HUMAN
• TTD ID: T84886
• Sequence:
  MAELPTTETPGDATLCSGRFTISTLLSSDEPSPPAAYDSSHPSHLTHSSTFCMRTFGYNT
  IDVVPTYEHYANSTQPGEPRKVRPTLADLHSFLKQEGRHLHALAFDSRPSHEMTDGLVEG
  EAGTSSEKNPEEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWIIILLSVT
  VTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAE
  TVRDLLQEYGAPIVDPINDIRIIAVVSVTVLLAISLAGMEWESKAQVLFFLVIMVSFANY
  LVGTLIPPSEDKASKGFFSYRADIFVQNLVPDWRGPDGTFFGMFSIFFPSATGILAGANI
  SGDLKDPAIAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGVLNDTVTPGWGACEGLA
  CSYGWNFTECTQQHSCHYGLINYYQTMSMVSGFAPLITAGIFGATLSSALACLVSAAKVF
  QCLCEDQLYPLIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSY
  ALINFSCFHASITNSPGWRPSFQYYNKWAALFGAIISVVIMFLLTWWAALIAIGVVLFLL
  LYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVD
  FVGTFTRNLSLMICGHVLIGPHKQRMPELQLIANGHTKWLNKRKIKAFYSDVIAEDLRRG
  VQILMQAAGLGRMKPNILVVGFKKNWQSAHPATVEDYIGILHDAFDFNYGVCVMRMREGL
  NVSKMMQAHINPVFDPAEDGKEASARVDPKALVKEEQATTIFQSEQGKKTIDIYWLFDDG
  GLTLLIPYLLGRKRRWSKCKIRVFVGGQINRMDQERKAIISLLSKFRLGFHEVHILPDIN
  QNPRAEHTKRFEDMIAPFRLNDGFKDEATVNEMRRDCPWKISDEEITKNRVKSLRQVRLN
  EIVLDYSRDAALIVITLPIGRKGKCPSSLYMAWLETLSQDLRPPVILIRGNQENVLTFYC
  Q
• Function: Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
• Reactome Pathway: Cation-coupled Chloride cotransporters (R-HSA-426117)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bendroflumethiazide	DM7EVLC	High blood pressure	BA00	Approved	[1]
Metolazone	DMB39LO	Edema	MG29	Approved	[2]
Polythiazide	DMCH80F	Edema	MG29	Approved	[2]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Thiazide-sensitive sodium-chloride cotransporter (SLC12A3) DTP Info
• Gene Name: SLC12A3

2 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bumetanide	DMRV7H0	Congestive heart failure	BD10	Approved	[3]
Metolazone	DMB39LO	Edema	MG29	Approved	[4]

References

• [1] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [2] The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon. J Clin Invest. 2001 Jul;108(2):215-22.
• [3] Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
• [4] Inhibition of binding of [3H]metolazone to rat kidney membrane by stilbene disulfonates. Biochem Pharmacol. 1991 Jun 1;41(11):1745-50.