Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIHSXO8)

• DOT Name: Ileal sodium/bile acid cotransporter (SLC10A2)
• Synonyms: Apical sodium-dependent bile acid transporter; ASBT; Ileal Na(+)/bile acid cotransporter; Ileal sodium-dependent bile acid transporter; IBAT; ISBT; Na(+)-dependent ileal bile acid transporter; Sodium/taurocholate cotransporting polypeptide, ileal; Solute carrier family 10 member 2
• Gene Name: SLC10A2
• Related Disease: Bile acid malabsorption, primary, 1
• UniProt ID: NTCP2_HUMAN
• Pfam ID: PF01758
• Sequence:
  MNDPNSCVDNATVCSGASCVVPESNFNNILSVVLSTVLTILLALVMFSMGCNVEIKKFLG
  HIKRPWGICVGFLCQFGIMPLTGFILSVAFDILPLQAVVVLIIGCCPGGTASNILAYWVD
  GDMDLSVSMTTCSTLLALGMMPLCLLIYTKMWVDSGSIVIPYDNIGTSLVSLVVPVSIGM
  FVNHKWPQKAKIILKIGSIAGAILIVLIAVVGGILYQSAWIIAPKLWIIGTIFPVAGYSL
  GFLLARIAGLPWYRCRTVAFETGMQNTQLCSTIVQLSFTPEELNVVFTFPLIYSIFQLAF
  AAIFLGFYVAYKKCHGKNKAEIPESKENGTEPESSFYKANGGFQPDEK
• Function: Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Transports various bile acids, unconjugated or conjugated, such as cholate and taurocholate. Also responsible for bile acid transport in the renal proximal tubules, a salvage mechanism that helps conserve bile acids (Probable). Works collaboratively with the Na(+)-taurocholate cotransporting polypeptide (NTCP), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation.
• Tissue Specificity: Mainly expressed in ileum and kidney, lower expression in cecum.
• KEGG Pathway: Bile secretion (hsa04976)
• Reactome Pathway: Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bile acid malabsorption, primary, 1	DISMUAH7	Limited	Autosomal recessive	[1]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Taurocholic acid	DM2LZ8F	Phase 1/2	Ileal sodium/bile acid cotransporter (SLC10A2) increases the transport of Taurocholic acid.	[5]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ileal sodium/bile acid cotransporter (SLC10A2).	[2]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Ileal sodium/bile acid cotransporter (SLC10A2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ileal sodium/bile acid cotransporter (SLC10A2).	[4]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [3] Resveratrol promotes degradation of the human bile acid transporter ASBT (SLC10A2). Biochem J. 2014 Apr 15;459(2):301-12. doi: 10.1042/BJ20131428.
• [4] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [5] Expression of drug transporters and drug metabolizing enzymes in the bladder urothelium in man and affinity of the bladder spasmolytic trospium chloride to transporters likely involved in its pharmacokinetics. Mol Pharm. 2015 Jan 5;12(1):171-8.