Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ4ZMHV)

• DOT Name: Anion exchange transporter (SLC26A7)
• Synonyms: Solute carrier family 26 member 7
• Gene Name: SLC26A7
• Related Disease: Congenital hypothyroidism
• UniProt ID: S26A7_HUMAN
• Pfam ID: PF01740 ; PF00916
• Sequence:
  MTGAKRKKKSMLWSKMHTPQCEDIIQWCRRRLPILDWAPHYNLKENLLPDTVSGIMLAVQ
  QVTQGLAFAVLSSVHPVFGLYGSLFPAIIYAIFGMGHHVATGTFALTSLISANAVERIVP
  QNMQNLTTQSNTSVLGLSDFEMQRIHVAAAVSFLGGVIQVAMFVLQLGSATFVVTEPVIS
  AMTTGAATHVVTSQVKYLLGMKMPYISGPLGFFYIYAYVFENIKSVRLEALLLSLLSIVV
  LVLVKELNEQFKRKIKVVLPVDLVLIIAASFACYCTNMENTYGLEVVGHIPQGIPSPRAP
  PMNILSAVITEAFGVALVGYVASLALAQGSAKKFKYSIDDNQEFLAHGLSNIVSSFFFCI
  PSAAAMGRTAGLYSTGAKTQVACLISCIFVLIVIYAIGPLLYWLPMCVLASIIVVGLKGM
  LIQFRDLKKYWNVDKIDWGIWVSTYVFTICFAANVGLLFGVVCTIAIVIGRFPRAMTVSI
  KNMKEMEFKVKTEMDSETLQQVKIISINNPLVFLNAKKFYTDLMNMIQKENACNQPLDDI
  SKCEQNTLLNSLSNGNCNEEASQSCPNEKCYLILDCSGFTFFDYSGVSMLVEVYMDCKGR
  SVDVLLAHCTASLIKAMTYYGNLDSEKPIFFESVSAAISHIHSNKNLSKLSDHSEV
• Function: Acts as an anion channel mediating the transport of chloride, sulfate and oxalate ions. Mediates the transport of bromide, iodide, nitrate, gluconate, thiocyanate and bicarbonate ions. Its permeability towards bicarbonate is weak and increases when pH is above 7. Mediates thiocyanate transport in retinal pigment epithelium cells. Mediates iodide transport in the thyroid gland, playing an important role in the synthesis of thyroid hormones and the maintenance of thyroid function. Although it is an anion channel, according to PubMed:12736153 and PubMed:32119864 it has been shown to exhibit chloride-bicarbonate exchanger activity.
• Tissue Specificity: Expressed in the thyroid gland (at protein level). Expressed in tonsillar high endothelial venule endothelial cells (HEVEC), placenta and in testis, expressed in a subgroup of basal cells in the epididymal ducts.
• KEGG Pathway: Gastric acid secretion (hsa04971)
• Reactome Pathway: Multifunctional anion exchangers (R-HSA-427601)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital hypothyroidism	DISL5XVU	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Anion exchange transporter (SLC26A7).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Anion exchange transporter (SLC26A7).	[3]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Anion exchange transporter (SLC26A7).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Anion exchange transporter (SLC26A7).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Anion exchange transporter (SLC26A7).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Anion exchange transporter (SLC26A7).	[6]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Anion exchange transporter (SLC26A7).	[7]

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] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [5] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [6] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [7] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.