Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGLGK1R)

• DOT Name: Kv channel-interacting protein 1 (KCNIP1)
• Synonyms: KChIP1; A-type potassium channel modulatory protein 1; Potassium channel-interacting protein 1; Vesicle APC-binding protein
• Gene Name: KCNIP1
• Related Disease:
  Atrial fibrillation
  Attention deficit hyperactivity disorder
  Cervical cancer
  Cervical carcinoma
  Multiple sclerosis
  Non-insulin dependent diabetes
  Schizophrenia
  Sclerosing cholangitis
  Amyotrophic lateral sclerosis
  Silver-Russell syndrome
  Status epilepticus seizure
  Syndromic X-linked intellectual disability Snyder type
• UniProt ID: KCIP1_HUMAN
• PDB ID: 1S1E; 2I2R; 2NZ0; 7E83; 7E84; 7F3F; 7W6N; 7W6T
• Pfam ID: PF13499 ; PF13833
• Sequence:
  MGAVMGTFSSLQTKQRRPSKDIAWWYYQYQRDKIEDELEMTMVCHRPEGLEQLEAQTNFT
  KRELQVLYRGFKNECPSGVVNEDTFKQIYAQFFPHGDASTYAHYLFNAFDTTQTGSVKFE
  DFVTALSILLRGTVHEKLRWTFNLYDINKDGYINKEEMMDIVKAIYDMMGKYTYPVLKED
  TPRQHVDVFFQKMDKNKDGIVTLDEFLESCQEDDNIMRSLQLFQNVM
• Function: Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Regulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND1/Kv4.1 and KCND2/Kv4.2 currents. Increases the presence of KCND2 at the cell surface.
• Tissue Specificity: Isoform 1 and isoform 2 are expressed in brain and kidney. Isoform 1 is also expressed in liver, pancreas, skeletal muscle, small intestine and testis. Isoform 2 is also expressed in lung, pancreas, leukocytes, prostate and thymus.
• Reactome Pathway: Phase 1 - inactivation of fast Na+ channels (R-HSA-5576894)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[6]
Sclerosing cholangitis	DIS7GZNB	Strong	Genetic Variation	[7]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[8]
Silver-Russell syndrome	DISSVJ1D	Limited	Biomarker	[9]
Status epilepticus seizure	DISY3BIC	Limited	Altered Expression	[9]
Syndromic X-linked intellectual disability Snyder type	DISN836E	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kv channel-interacting protein 1 (KCNIP1).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Kv channel-interacting protein 1 (KCNIP1).	[11]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Kv channel-interacting protein 1 (KCNIP1).	[12]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Kv channel-interacting protein 1 (KCNIP1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Kv channel-interacting protein 1 (KCNIP1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Kv channel-interacting protein 1 (KCNIP1).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Kv channel-interacting protein 1 (KCNIP1).	[17]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Kv channel-interacting protein 1 (KCNIP1).	[14]

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 Kv channel-interacting protein 1 (KCNIP1).	[13]

References

• [1] Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation.Nat Commun. 2016 Feb 2;7:10190. doi: 10.1038/ncomms10190.
• [2] Attention-deficit/hyperactivity disorder associated with KChIP1 rs1541665 in Kv channels accessory proteins.PLoS One. 2017 Nov 27;12(11):e0188678. doi: 10.1371/journal.pone.0188678. eCollection 2017.
• [3] KF-finder: identification of key factors from host-microbial networks in cervical cancer.BMC Syst Biol. 2018 Apr 24;12(Suppl 4):54. doi: 10.1186/s12918-018-0566-x.
• [4] Post-mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphisms.Brain Pathol. 2020 Jan;30(1):106-119. doi: 10.1111/bpa.12760. Epub 2019 Jul 23.
• [5] Divergent patterns of genic copy number variation in KCNIP1 gene reveal risk locus of type 2 diabetes in Chinese population.Endocr J. 2018 May 28;65(5):537-545. doi: 10.1507/endocrj.EJ17-0496. Epub 2018 Feb 27.
• [6] Genome-wide association study of paliperidone efficacy.Pharmacogenet Genomics. 2017 Jan;27(1):7-18. doi: 10.1097/FPC.0000000000000250.
• [7] Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.Gut. 2018 Aug;67(8):1517-1524. doi: 10.1136/gutjnl-2016-313598. Epub 2017 Aug 4.
• [8] Protein aggregation due to nsSNP resulting in P56S VABP protein is associated with amyotrophic lateral sclerosis.J Theor Biol. 2014 Aug 7;354:72-80. doi: 10.1016/j.jtbi.2014.03.027. Epub 2014 Mar 27.
• [9] Saikosaponin A modulates remodeling of Kv4.2-mediated A-type voltage-gated potassium currents in rat chronic temporal lobe epilepsy.Drug Des Devel Ther. 2018 Sep 11;12:2945-2958. doi: 10.2147/DDDT.S166408. eCollection 2018.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [13] 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.
• [14] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
• [15] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [16] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [17] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.