Details of Drug Off-Target (DOT)

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

DOT Name	Barttin (BSND)
Gene Name	BSND
Related Disease	Bartter disease type 4A ( ) Acinar cell carcinoma ( ) Bartonellosis ( ) Bartter syndrome ( ) Clear cell renal carcinoma ( ) Deafness ( ) Dent disease type 1 ( ) Epstein barr virus infection ( ) Gastroesophageal reflux disease ( ) Hyperaldosteronism ( ) Kidney failure ( ) Nasopharyngeal carcinoma ( ) Renal cell carcinoma ( ) Sensorineural hearing loss disorder ( ) Stomach cancer ( ) Allergic rhinitis ( ) Carcinoma ( ) Cardiovascular disease ( ) Chronic renal failure ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) End-stage renal disease ( ) Nephrocalcinosis ( ) Niemann-Pick disease type C ( ) Pancreatic cancer ( ) Bartter syndrome type 4 ( ) Hearing loss, autosomal recessive ( ) Essential hypertension ( ) Hypocalcemia ( )
UniProt ID	BSND_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF15462
Sequence	MADEKTFRIGFIVLGLFLLALGTFLMSHDRPQVYGTFYAMGSVMVIGGIIWSMCQCYPKI TFVPADSDFQGILSPKAMGLLENGLAAEMKSPSPQPPYVRLWEEAAYDQSLPDFSHIQMK VMSYSEDHRSLLAPEMGQPKLGTSDGGEGGPGDVQAWMEAAVVIHKGSDESEGERRLTQS WPGPLACPQGPAPLASFQDDLDMDSSEGSSPNASPHDREEACSPQQEPQGCRCPLDRFQD FALIDAPTLEDEPQEGQQWEIALPNNWQRYPRTKVEEKEASDTGGEEPEKEEEDLYYGLP DGAGDLLPDKELGFEPDTQG
Function	Functions as a beta-subunit for CLCNKA and CLCNKB chloride channels. In the kidney CLCNK/BSND heteromers mediate chloride reabsorption by facilitating its basolateral efflux. In the stria, CLCNK/BSND channels drive potassium secretion by recycling chloride for the basolateral SLC12A2 cotransporter.
Tissue Specificity	Expressed primarily in kidney. Expressed in specific nephron segments and in the stria vascularis of the inner ear.
Reactome Pathway	Stimuli-sensing channels (R-HSA-2672351 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Bartter disease type 4A	DISUEZHY	Definitive	Autosomal recessive	[1]
Acinar cell carcinoma	DIS37Y0J	Strong	Biomarker	[2]
Bartonellosis	DISMKP1N	Strong	Biomarker	[3]
Bartter syndrome	DIS7D44B	Strong	Genetic Variation	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[2]
Deafness	DISKCLH4	Strong	Biomarker	[5]
Dent disease type 1	DISNGJIQ	Strong	Altered Expression	[6]
Epstein barr virus infection	DISOO0WT	Strong	Biomarker	[7]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[8]
Hyperaldosteronism	DIS3WGAL	Strong	Genetic Variation	[9]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[10]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[2]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[12]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[14]
Carcinoma	DISH9F1N	moderate	Altered Expression	[15]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[16]
Chronic renal failure	DISGG7K6	moderate	Altered Expression	[17]
Coronary atherosclerosis	DISKNDYU	moderate	Genetic Variation	[16]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[16]
End-stage renal disease	DISXA7GG	moderate	Altered Expression	[17]
Nephrocalcinosis	DIS5ZVJP	moderate	Genetic Variation	[18]
Niemann-Pick disease type C	DIS492ZO	moderate	Altered Expression	[19]
Pancreatic cancer	DISJC981	moderate	Biomarker	[20]
Bartter syndrome type 4	DISH9V6T	Supportive	Autosomal recessive	[10]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[21]
Essential hypertension	DIS7WI98	Limited	Genetic Variation	[22]
Hypocalcemia	DISTCK2W	Limited	Genetic Variation	[23]
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⏷ Show the Full List of 29 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 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 Barttin (BSND).	[24]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Barttin (BSND).	[25]
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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 Barttin (BSND).	[26]
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References

1	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2	BSND is a Novel Immunohistochemical Marker for Oncocytic Salivary Gland Tumors.Pathol Oncol Res. 2018 Apr;24(2):439-444. doi: 10.1007/s12253-017-0248-9. Epub 2017 May 3.
3	Detection of Bartonella in cat scratch disease using a single-step PCR assay kit.J Med Microbiol. 2017 Nov;66(11):1596-1601. doi: 10.1099/jmm.0.000626. Epub 2017 Oct 25.
4	Role of zebrafish ClC-K/barttin channels in apical kidney chloride reabsorption.J Physiol. 2019 Aug;597(15):3969-3983. doi: 10.1113/JP278069. Epub 2019 Jul 3.
5	Linkage of infantile Bartter syndrome with sensorineural deafness to chromosome 1p.Am J Hum Genet. 1998 Feb;62(2):355-61. doi: 10.1086/301708.
6	Barttin Regulates the Subcellular Localization and Posttranslational Modification of Human Cl(-)/H(+) Antiporter ClC-5.Front Physiol. 2018 Oct 23;9:1490. doi: 10.3389/fphys.2018.01490. eCollection 2018.
7	Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells.Virol J. 2013 Oct 26;10:314. doi: 10.1186/1743-422X-10-314.
8	Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review.Expert Rev Clin Pharmacol. 2018 Dec;11(12):1195-1208. doi: 10.1080/17512433.2018.1540298. Epub 2018 Dec 6.
9	Two novel homozygous missense mutations identified in the BSND gene in Moroccan patients with Bartter's syndrome.Int J Pediatr Otorhinolaryngol. 2018 Oct;113:46-50. doi: 10.1016/j.ijporl.2018.07.010. Epub 2018 Jul 10.
10	Severe manifestation of Bartter syndrome Type IV caused by a novel insertion mutation in the BSND gene. Clin Nephrol. 2014 May;81(5):363-8. doi: 10.5414/CN107687.
11	Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-B pathway.Cancer Lett. 2019 Apr 10;447:33-40. doi: 10.1016/j.canlet.2019.01.022. Epub 2019 Jan 23.
12	Activation of renal ClC-K chloride channels depends on an intact N terminus of their accessory subunit barttin.J Biol Chem. 2018 Jun 1;293(22):8626-8637. doi: 10.1074/jbc.RA117.000860. Epub 2018 Apr 19.
13	Cellular oncomiR orthologue in EBV oncogenesis.Comput Biol Med. 2011 Oct;41(10):891-8. doi: 10.1016/j.compbiomed.2011.07.007. Epub 2011 Aug 30.
14	Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis.BMC Med Genomics. 2014 Aug 2;7:48. doi: 10.1186/1755-8794-7-48.
15	Dissecting the regulation of EBV's BART miRNAs in carcinomas.Virology. 2017 May;505:148-154. doi: 10.1016/j.virol.2017.02.013. Epub 2017 Mar 1.
16	Detection of Left Ventricular Hypertrophy Using Bayesian Additive Regression Trees: The MESA.J Am Heart Assoc. 2019 Mar 5;8(5):e009959. doi: 10.1161/JAHA.118.009959.
17	Renal dysfunction and barttin expression in Bartter syndrome Type IV associated with a G47R mutation in BSND in a family.Clin Nephrol. 2011 Feb;75 Suppl 1:69-74.
18	Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome.Nephrol Dial Transplant. 2009 May;24(5):1455-64. doi: 10.1093/ndt/gfn689. Epub 2008 Dec 18.
19	Interplay of Viral Infection, Host Cell Factors and Tumor Microenvironment in the Pathogenesis of Nasopharyngeal Carcinoma.Cancers (Basel). 2018 Apr 4;10(4):106. doi: 10.3390/cancers10040106.
20	BART inhibits pancreatic cancer cell invasion by PKC inactivation through binding to ANX7.PLoS One. 2012;7(4):e35674. doi: 10.1371/journal.pone.0035674. Epub 2012 Apr 19.
21	Genetic Hearing Loss Overview. 1999 Feb 14 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
22	CLCNKB-T481S and essential hypertension in a Ghanaian population.J Hypertens. 2009 Feb;27(2):298-304. doi: 10.1097/hjh.0b013e3283140c9e.
23	Bartter's and Gitelman's syndromes: from gene to clinic.Nephron Physiol. 2004;96(3):p65-78. doi: 10.1159/000076752.
24	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.
25	Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
26	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.