Details of Drug Off-Target (DOT)

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

• DOT Name: Gap junction beta-4 protein (GJB4)
• Synonyms: Connexin-30.3; Cx30.3
• Gene Name: GJB4
• Related Disease:
  Erythrokeratodermia variabilis et progressiva 2
  Erythrokeratodermia variabilis
• UniProt ID: CXB4_HUMAN
• Pfam ID: PF00029
• Sequence:
  MNWAFLQGLLSGVNKYSTVLSRIWLSVVFIFRVLVYVVAAEEVWDDEQKDFVCNTKQPGC
  PNVCYDEFFPVSHVRLWALQLILVTCPSLLVVMHVAYREERERKHHLKHGPNAPSLYDNL
  SKKRGGLWWTYLLSLIFKAAVDAGFLYIFHRLYKDYDMPRVVACSVEPCPHTVDCYISRP
  TEKKVFTYFMVTTAAICILLNLSEVFYLVGKRCMEIFGPRHRRPRCRECLPDTCPPYVLS
  QGGHPEDGNSVLMKAGSAPVDAGGYP
• Function: Structural component of gap junctions. Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane. Small molecules and ions diffuse from one cell to a neighboring cell via the central pore.
• Reactome Pathway: Gap junction assembly (R-HSA-190861)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Erythrokeratodermia variabilis et progressiva 2	DISLV4SZ	Strong	Autosomal dominant	[1]
Erythrokeratodermia variabilis	DIS4BMUQ	Supportive	Autosomal dominant	[2]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Gap junction beta-4 protein (GJB4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Gap junction beta-4 protein (GJB4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Gap junction beta-4 protein (GJB4).	[5]

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] Novel mutation in GJB4 gene (connexin 30.3) in a family with erythrokeratodermia variabilis. Acta Derm Venereol. 2013 Mar 27;93(2):193-5. doi: 10.2340/00015555-1436.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.