Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9QQDZB)

• DOT Name: Gap junction beta-6 protein (GJB6)
• Synonyms: Connexin-30; Cx30
• Gene Name: GJB6
• Related Disease:
  Clouston syndrome
  Autosomal dominant nonsyndromic hearing loss 3B
  Autosomal dominant nonsyndromic hearing loss
  Hearing loss, autosomal recessive
  KID syndrome
  Autosomal recessive nonsyndromic hearing loss 1B
  Nonsyndromic genetic hearing loss
• UniProt ID: CXB6_HUMAN
• Pfam ID: PF00029
• Sequence:
  MDWGTLHTFIGGVNKHSTSIGKVWITVIFIFRVMILVVAAQEVWGDEQEDFVCNTLQPGC
  KNVCYDHFFPVSHIRLWALQLIFVSTPALLVAMHVAYYRHETTRKFRRGEKRNDFKDIED
  IKKQKVRIEGSLWWTYTSSIFFRIIFEAAFMYVFYFLYNGYHLPWVLKCGIDPCPNLVDC
  FISRPTEKTVFTIFMISASVICMLLNVAELCYLLLKVCFRRSKRAQTQKNHPNHALKESK
  QNEMNELISDSGQNAITGFPS
• Function: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
• Reactome Pathway: Gap junction assembly (R-HSA-190861)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clouston syndrome	DISZRYX4	Definitive	Autosomal dominant	[1]
Autosomal dominant nonsyndromic hearing loss 3B	DISHW62E	Moderate	Autosomal dominant	[2]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[3]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[3]
KID syndrome	DISRBJLW	Supportive	Autosomal dominant	[4]
Autosomal recessive nonsyndromic hearing loss 1B	DIS8LD8U	Limited	Autosomal recessive	[2]
Nonsyndromic genetic hearing loss	DISZX61P	Refuted	Autosomal recessive	[1]

6 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 Gap junction beta-6 protein (GJB6).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Gap junction beta-6 protein (GJB6).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Gap junction beta-6 protein (GJB6).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Gap junction beta-6 protein (GJB6).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Gap junction beta-6 protein (GJB6).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Gap junction beta-6 protein (GJB6).	[10]

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] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] 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.
• [4] Genetic heterogeneity of KID syndrome: identification of a Cx30 gene (GJB6) mutation in a patient with KID syndrome and congenital atrichia. J Invest Dermatol. 2004 May;122(5):1108-13. doi: 10.1111/j.0022-202X.2004.22518.x.
• [5] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.