Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSLTR4Y)

DOT Name Kin of IRRE-like protein 2 (KIRREL2)
Synonyms Kin of irregular chiasm-like protein 2; Nephrin-like protein 3
Gene Name KIRREL2
Related Disease
Chronic kidney disease ( )
Chronic renal failure ( )
Brain disease ( )
Kidney failure ( )
UniProt ID
KIRR2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF08205 ; PF07679 ; PF13927
Sequence
MLRMRVPALLVLLFCFRGRAGPSPHFLQQPEDLVVLLGEEARLPCALGAYWGLVQWTKSG
LALGGQRDLPGWSRYWISGNAANGQHDLHIRPVELEDEASYECQATQAGLRSRPAQLHVL
VPPEAPQVLGGPSVSLVAGVPANLTCRSRGDARPTPELLWFRDGVLLDGATFHQTLLKEG
TPGSVESTLTLTPFSHDDGATFVCRARSQALPTGRDTAITLSLQYPPEVTLSASPHTVQE
GEKVIFLCQATAQPPVTGYRWAKGGSPVLGARGPRLEVVADASFLTEPVSCEVSNAVGSA
NRSTALDVLFGPILQAKPEPVSVDVGEDASFSCAWRGNPLPRVTWTRRGGAQVLGSGATL
RLPSVGPEDAGDYVCRAEAGLSGLRGGAAEARLTVNAPPVVTALHSAPAFLRGPARLQCL
VFASPAPDAVVWSWDEGFLEAGSQGRFLVETFPAPESRGGLGPGLISVLHISGTQESDFS
RSFNCSARNRLGEGGAQASLGRRDLLPTVRIVAGVAAATTTLLMVITGVALCCWRHSKAS
ASFSEQKNLMRIPGSSDGSSSRGPEEEETGSREDRGPIVHTDHSDLVLEEEGTLETKDPT
NGYYKVRGVSVSLSLGEAPGGGLFLPPPSPLGPPGTPTFYDFNPHLGMVPPCRLYRARAG
YLTTPHPRAFTSYIKPTSFGPPDLAPGTPPFPYAAFPTPSHPRLQTHV
Function May regulate basal insulin secretion.
Tissue Specificity Highly expressed in beta-cells of the pancreatic islets.
Reactome Pathway
Nephrin family interactions (R-HSA-373753 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic kidney disease DISW82R7 Definitive Genetic Variation [1]
Chronic renal failure DISGG7K6 Definitive Genetic Variation [1]
Brain disease DIS6ZC3X Strong Altered Expression [2]
Kidney failure DISOVQ9P Strong Genetic Variation [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Kin of IRRE-like protein 2 (KIRREL2). [4]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Kin of IRRE-like protein 2 (KIRREL2). [6]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Kin of IRRE-like protein 2 (KIRREL2). [7]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Kin of IRRE-like protein 2 (KIRREL2). [8]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Kin of IRRE-like protein 2 (KIRREL2). [10]
Paraoxon DMN4ZKC Investigative Paraoxon increases the expression of Kin of IRRE-like protein 2 (KIRREL2). [11]
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⏷ Show the Full List of 6 Drug(s)
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 Kin of IRRE-like protein 2 (KIRREL2). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Kin of IRRE-like protein 2 (KIRREL2). [9]
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References

1 Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms.J Am Soc Nephrol. 2018 May;29(5):1513-1524. doi: 10.1681/ASN.2017101099. Epub 2018 Mar 15.
2 Regulation of hippocampal long term depression by Neuroligin 1.Neuropharmacology. 2018 Dec;143:205-216. doi: 10.1016/j.neuropharm.2018.09.035. Epub 2018 Sep 26.
3 A functional variant in NEPH3 gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population.PLoS One. 2017 Mar 23;12(3):e0174274. doi: 10.1371/journal.pone.0174274. eCollection 2017.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 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.
6 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
7 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
8 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
9 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.
10 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
11 Genomic and phenotypic alterations of the neuronal-like cells derived from human embryonal carcinoma stem cells (NT2) caused by exposure to organophosphorus compounds paraoxon and mipafox. Int J Mol Sci. 2014 Jan 9;15(1):905-26. doi: 10.3390/ijms15010905.