Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNVZ8Z1)

• DOT Name: Steroid transmembrane transporter SLC22A24 (SLC22A24)
• Synonyms: Solute carrier family 22 member 24
• Gene Name: SLC22A24
• Related Disease:
  Acute kidney injury
  Advanced cancer
  Cardiovascular disease
• UniProt ID: S22AO_HUMAN
• Pfam ID: PF00083
• Sequence:
  MGFDVLLDQVGGMGRFQICLIAFFCITNILLFPNIVLENFTAFTPSHRCWVPLLDNDTVS
  DNDTGTLSKDDLLRISIPLDSNLRPQKCQRFIHPQWQLLHLNGTFPNTNEPDTEPCVDGW
  VYDRSSFLSTIVTEWDLVCESQSLKSMVQSLFMAGSLLGGLIYGHLSDRVGRKIICKLCF
  LQLAISNTCAAFAPTFLVYCILRFLAGFSTMTILGNTFILSLEWTLPRSRSMTIMVLLCS
  YSVGQMLLGGLAFAIQDWHILQLTVSTPIIVLFLSSWKMVESARWLIINNQLDEGLKELR
  RVAHINGKKNTEETLTTELVRSTMKKELDAVRIKTSIFSLFRAPKLRMRVFGLCFVRFAI
  TVPFYGLILNLQHLGSNVSLFQILCGAVTFTARCVSLLTLNHMGRRISQILFTFPVGLFI
  LVNTFLPQEMQILRVVLATLGIGSVSAASNSASVHHNELVPTILRSTVAGINAVSGRTGA
  ALAPLLMTLMAYSPHLPWISYGVFPILAVPVILLLPETRDLPLPNTIQDVENDRKDSRNI
  KQEDTCMKVTQF
• Function: Renal transmembrane organic anion/dicarboxylate exchanger that participates in the reabsorption of conjugated steroids including estradiol-17beta-D-glucuronide (or 17beta-estradiol 17-O-(beta-D-glucuronate)), androstanediol glucuronide (or 5alpha-androstane-3alpha,17beta-diol 3-O-(beta-D-glucuronate)), and estrone 3-sulfate, as well as bile acids taurocholate and glycocholate, driven by an outward gradient of dicarboxylates such as glutarate or succinate; [Isoform 2]: Similar uptake function as Isoform 1; [Isoform 3]: Lack of transporter activity.
• Tissue Specificity: .Localized to the kidney . Highly specific expression pattern in the nephron, localized to segment 3 of the proximal tubule .; [Isoform 2]: Localized to the kidney . Highly specific expression pattern in the nephron, localized to segment 3 of the proximal tubule .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute kidney injury	DISXZG0T	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Steroid transmembrane transporter SLC22A24 (SLC22A24).	[4]

References

• [1] Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity.Chem Res Toxicol. 2015 Aug 17;28(8):1595-602. doi: 10.1021/acs.chemrestox.5b00176. Epub 2015 Aug 7.
• [2] Status and significance of CpG island methylator phenotype in endometrial cancer.Gynecol Obstet Invest. 2011;72(3):183-91. doi: 10.1159/000324496. Epub 2011 Sep 27.
• [3] Unraveling the functional role of the orphan solute carrier, SLC22A24 in the transport of steroid conjugates through metabolomic and genome-wide association studies.PLoS Genet. 2019 Sep 25;15(9):e1008208. doi: 10.1371/journal.pgen.1008208. eCollection 2019 Sep.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.