Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYRO19B)

• DOT Name: Solute carrier organic anion transporter family member 1C1 (SLCO1C1)
• Synonyms: Organic anion transporter 1C1; OATP1C1; Organic anion transporter F; OATP-F; Organic anion transporter polypeptide-related protein 5; OAT-RP-5; OATP-RP5; Organic anion-transporting polypeptide 14; OATP-14; Solute carrier family 21 member 14; Thyroxine transporter
• Gene Name: SLCO1C1
• Related Disease: Complex neurodevelopmental disorder
• UniProt ID: SO1C1_HUMAN
• Pfam ID: PF07648 ; PF03137
• Sequence:
  MDTSSKENIQLFCKTSVQPVGRPSFKTEYPSSEEKQPCCGELKVFLCALSFVYFAKALAE
  GYLKSTITQIERRFDIPSSLVGVIDGSFEIGNLLVITFVSYFGAKLHRPKIIGAGCVIMG
  VGTLLIAMPQFFMEQYKYERYSPSSNSTLSISPCLLESSSQLPVSVMEKSKSKISNECEV
  DTSSSMWIYVFLGNLLRGIGETPIQPLGIAYLDDFASEDNAAFYIGCVQTVAIIGPIFGF
  LLGSLCAKLYVDIGFVNLDHITITPKDPQWVGAWWLGYLIAGIISLLAAVPFWYLPKSLP
  RSQSREDSNSSSEKSKFIIDDHTDYQTPQGENAKIMEMARDFLPSLKNLFGNPVYFLYLC
  TSTVQFNSLFGMVTYKPKYIEQQYGQSSSRANFVIGLINIPAVALGIFSGGIVMKKFRIS
  VCGAAKLYLGSSVFGYLLFLSLFALGCENSDVAGLTVSYQGTKPVSYHERALFSDCNSRC
  KCSETKWEPMCGENGITYVSACLAGCQTSNRSGKNIIFYNCTCVGIAASKSGNSSGIVGR
  CQKDNGCPQMFLYFLVISVITSYTLSLGGIPGYILLLRCIKPQLKSFALGIYTLAIRVLA
  GIPAPVYFGVLIDTSCLKWGFKRCGSRGSCRLYDSNVFRHIYLGLTVILGTVSILLSIAV
  LFILKKNYVSKHRSFITKRERTMVSTRFQKENYTTSDHLLQPNYWPGKETQL
• Function: Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane. Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases. Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency. Transports T4 and E1S in a pH-insensitive manner. Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain.
• Tissue Specificity: Highly expressed in brain and in Leydig cells in testis . Localized in nests of Leydig cells (at protein level) . Expressed in choroid plexus (at protein level) . Not strongly enriched in cerebral microvessels .
• KEGG Pathway: Thyroid hormone sig.ling pathway (hsa04919)
• Reactome Pathway: Transport of organic anions (R-HSA-879518)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Solute carrier organic anion transporter family member 1C1 (SLCO1C1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Solute carrier organic anion transporter family member 1C1 (SLCO1C1).	[3]

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] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 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.