Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT811KOM)

• DOT Name: Potassium voltage-gated channel subfamily C member 3 (KCNC3)
• Synonyms: KSHIIID; Voltage-gated potassium channel subunit Kv3.3
• Gene Name: KCNC3
• Related Disease: Spinocerebellar ataxia type 13
• UniProt ID: KCNC3_HUMAN
• Pfam ID: PF02214 ; PF00520 ; PF11404
• Sequence:
  MLSSVCVSSFRGRQGASKQQPAPPPQPPESPPPPPLPPQQQQPAQPGPAASPAGPPAPRG
  PGDRRAEPCPGLPAAAMGRHGGGGGDSGKIVINVGGVRHETYRSTLRTLPGTRLAGLTEP
  EAAARFDYDPGADEFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELGFWGIDETD
  VEACCWMTYRQHRDAEEALDSFEAPDPAGAANAANAAGAHDGGLDDEAGAGGGGLDGAGG
  ELKRLCFQDAGGGAGGPPGGAGGAGGTWWRRWQPRVWALFEDPYSSRAARYVAFASLFFI
  LISITTFCLETHEGFIHISNKTVTQASPIPGAPPENITNVEVETEPFLTYVEGVCVVWFT
  FEFLMRITFCPDKVEFLKSSLNIIDCVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVR
  ILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERIGADPDDIL
  GSNHTYFKNIPIGFWWAVVTMTTLGYGDMYPKTWSGMLVGALCALAGVLTIAMPVPVIVN
  NFGMYYSLAMAKQKLPKKKNKHIPRPPQPGSPNYCKPDPPPPPPPHPHHGSGGISPPPPI
  TPPSMGVTVAGAYPAGPHTHPGLLRGGAGGLGIMGLPPLPAPGEPCPLAQEEVIEINRAD
  PRPNGDPAAAALAHEDCPAIDQPAMSPEDKSPITPGSRGRYSRDRACFLLTDYAPSPDGS
  IRKATGAPPLPPQDWRKPGPPSFLPDLNANAAAWISP
• Function: Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics. It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells. Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis. Required for normal motor function. Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex.
• KEGG Pathway: Spinocerebellar ataxia (hsa05017)
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spinocerebellar ataxia type 13	DISXQKJA	Strong	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Potassium voltage-gated channel subfamily C member 3 (KCNC3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Potassium voltage-gated channel subfamily C member 3 (KCNC3).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Potassium voltage-gated channel subfamily C member 3 (KCNC3).	[4]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Potassium voltage-gated channel subfamily C member 3 (KCNC3).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Potassium voltage-gated channel subfamily C member 3 (KCNC3).	[7]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Potassium voltage-gated channel subfamily C member 3 (KCNC3).	[5]

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 decreases the methylation of Potassium voltage-gated channel subfamily C member 3 (KCNC3).	[6]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [6] 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.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.