Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8P734M)

• DOT Name: Potassium channel subfamily K member 9 (KCNK9)
• Synonyms: Acid-sensitive potassium channel protein TASK-3; TWIK-related acid-sensitive K(+) channel 3; Two pore potassium channel KT3.2; Two pore K(+) channel KT3.2
• Gene Name: KCNK9
• Related Disease: Birk-Barel syndrome
• UniProt ID: KCNK9_HUMAN
• PDB ID: 3P1N; 3P1O; 3P1P; 3P1Q; 3P1R; 3P1S; 3SMK; 3SML; 3SMM; 3SMN; 3SMO; 3SP5; 3SPR; 3UX0; 4FR3; 6GHP
• Pfam ID: PF07885
• Sequence:
  MKRQNVRTLSLIVCTFTYLLVGAAVFDALESDHEMREEEKLKAEEIRIKGKYNISSEDYR
  QLELVILQSEPHRAGVQWKFAGSFYFAITVITTIGYGHAAPGTDAGKAFCMFYAVLGIPL
  TLVMFQSLGERMNTFVRYLLKRIKKCCGMRNTDVSMENMVTVGFFSCMGTLCIGAAAFSQ
  CEEWSFFHAYYYCFITLTTIGFGDYVALQTKGALQKKPLYVAFSFMYILVGLTVIGAFLN
  LVVLRFLTMNSEDERRDAEERASLAGNRNSMVIHIPEEPRPSRPRYKADVPDLQSVCSCT
  CYRSQDYGGRSVAPQNSFSAKLAPHYFHSISYKIEEISPSTLKNSLFPSPISSISPGLHS
  FTDHQRLMKRRKSV
• Function: pH-dependent, voltage-insensitive, background potassium channel protein.
• Tissue Specificity: Mainly found in the cerebellum. Also found in adrenal gland, kidney and lung.
• KEGG Pathway: Aldosterone synthesis and secretion (hsa04925)
• Reactome Pathway:
  Phase 4 - resting membrane potential (R-HSA-5576886)
  TWIK-releated acid-sensitive K+ channel (TASK) (R-HSA-1299316)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Birk-Barel syndrome	DISH4Q9M	Strong	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Potassium channel subfamily K member 9 (KCNK9).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Potassium channel subfamily K member 9 (KCNK9).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Potassium channel subfamily K member 9 (KCNK9).	[4]

2 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 Potassium channel subfamily K member 9 (KCNK9).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Potassium channel subfamily K member 9 (KCNK9).	[6]

References

• [1] Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9. Am J Hum Genet. 2008 Aug;83(2):193-9. doi: 10.1016/j.ajhg.2008.07.010.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.