Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3HPMBV)

• DOT Name: Chloride channel protein 1 (CLCN1)
• Synonyms: ClC-1; Chloride channel protein, skeletal muscle
• Gene Name: CLCN1
• Related Disease:
  Myotonia congenita, autosomal dominant
  Myotonia congenita, autosomal recessive
  Thomsen and Becker disease
• UniProt ID: CLCN1_HUMAN
• PDB ID: 6COY; 6COZ; 6QV6; 6QVB; 6QVC; 6QVD; 6QVU
• Pfam ID: PF00654
• Sequence:
  MEQSRSQQRGGEQSWWGSDPQYQYMPFEHCTSYGLPSENGGLQHRLRKDAGPRHNVHPTQ
  IYGHHKEQFSDREQDIGMPKKTGSSSTVDSKDEDHYSKCQDCIHRLGQVVRRKLGEDGIF
  LVLLGLLMALVSWSMDYVSAKSLQAYKWSYAQMQPSLPLQFLVWVTFPLVLILFSALFCH
  LISPQAVGSGIPEMKTILRGVVLKEYLTMKAFVAKVVALTAGLGSGIPVGKEGPFVHIAS
  ICAAVLSKFMSVFCGVYEQPYYYSDILTVGCAVGVGCCFGTPLGGVLFSIEVTSTYFAVR
  NYWRGFFAATFSAFVFRVLAVWNKDAVTITALFRTNFRMDFPFDLKELPAFAAIGICCGL
  LGAVFVYLHRQVMLGVRKHKALSQFLAKHRLLYPGIVTFVIASFTFPPGMGQFMAGELMP
  REAISTLFDNNTWVKHAGDPESLGQSAVWIHPRVNVVIIIFLFFVMKFWMSIVATTMPIP
  CGGFMPVFVLGAAFGRLVGEIMAMLFPDGILFDDIIYKILPGGYAVIGAAALTGAVSHTV
  STAVICFELTGQIAHILPMMVAVILANMVAQSLQPSLYDSIIQVKKLPYLPDLGWNQLSK
  YTIFVEDIMVRDVKFVSASYTYGELRTLLQTTTVKTLPLVDSKDSMILLGSVERSELQAL
  LQRHLCPERRLRAAQEMARKLSELPYDGKARLAGEGLPGAPPGRPESFAFVDEDEDEDLS
  GKSELPPSLALHPSTTAPLSPEEPNGPLPGHKQQPEAPEPAGQRPSIFQSLLHCLLGRAR
  PTKKKTTQDSTDLVDNMSPEEIEAWEQEQLSQPVCFDSCCIDQSPFQLVEQTTLHKTHTL
  FSLLGLHLAYVTSMGKLRGVLALEELQKAIEGHTKSGVQLRPPLASFRNTTSTRKSTGAP
  PSSAENWNLPEDRPGATGTGDVIAASPETPVPSPSPEPPLSLAPGKVEGELEELELVESP
  GLEEELADILQGPSLRSTDEEDEDELIL
• Function: Voltage-gated chloride channel. Plays an important role in membrane repolarization in skeletal muscle cells after muscle contraction. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (Probable). The absence of conserved gating glutamate residues is typical for family members that function as channels (Probable).
• Tissue Specificity: Predominantly expressed in skeletal muscles.
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myotonia congenita, autosomal dominant	DISAC9U9	Strong	Autosomal dominant	[1]
Myotonia congenita, autosomal recessive	DISQ2NAW	Strong	Autosomal recessive	[1]
Thomsen and Becker disease	DISXXIMR	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Chloride channel protein 1 (CLCN1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Chloride channel protein 1 (CLCN1).	[3]

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 Chloride channel protein 1 (CLCN1).	[4]

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] Myotonia Congenita. 2005 Aug 3 [updated 2021 Feb 25]. 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.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [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.