Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJIT7FJ)

• DOT Name: Sodium/potassium/calcium exchanger 5 (SLC24A5)
• Synonyms: Na(+)/K(+)/Ca(2+)-exchange protein 5; Solute carrier family 24 member 5
• Gene Name: SLC24A5
• Related Disease:
  Oculocutaneous albinism type 6
  Oculocutaneous albinism type 7
• UniProt ID: NCKX5_HUMAN
• Pfam ID: PF01699
• Sequence:
  MQTKGGQTWARRALLLGILWATAHLPLSGTSLPQRLPRATGNSTQCVISPSSEFPEGFFT
  RQERRDGGIIIYFLIIVYMFMAISIVCDEYFLPSLEIISESLGLSQDVAGTTFMAAGSSA
  PELVTAFLGVFITKGDIGISTILGSAIYNLLGICAACGLLSNTVSTLSCWPLFRDCAAYT
  ISAAAVLGIIYDNQVYWYEGALLLLIYGLYVLVLCFDIKINQYIIKKCSPCCACLAKAME
  RSEQQPLMGWEDEGQPFIRRQSRTDSGIFYEDSGYSQLSISLHGLSQVSEDPPSVFNMPE
  ADLKRIFWVLSLPIITLLFLTTPDCRKKFWKNYFVITFFMSAIWISAFTYILVWMVTITG
  ETLEIPDTVMGLTLLAAGTSIPDTIASVLVARKGKGDMAMSNIVGSNVFDMLCLGIPWFI
  KTAFINGSAPAEVNSRGLTYITISLNISIIFLFLAVHFNGWKLDRKLGIVCLLSYLGLAT
  LSVLYELGIIGNNKIRGCGG
• Function: Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+). Involved in pigmentation, possibly by participating in ion transport in melanosomes. Predominant sodium-calcium exchanger in melanocytes.
• Reactome Pathway:
  Defective SLC24A5 causes oculocutaneous albinism 6 (OCA6) (R-HSA-5619036)
  Sodium/Calcium exchangers (R-HSA-425561)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oculocutaneous albinism type 6	DISW4841	Definitive	Autosomal recessive	[1]
Oculocutaneous albinism type 7	DISVVH65	Definitive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium/potassium/calcium exchanger 5 (SLC24A5).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sodium/potassium/calcium exchanger 5 (SLC24A5).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium/potassium/calcium exchanger 5 (SLC24A5).	[5]

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] Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. J Invest Dermatol. 2013 Jul;133(7):1834-40. doi: 10.1038/jid.2013.49. Epub 2013 Jan 30.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] 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.