Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP3CIAV)

• DOT Name: Calcium homeostasis modulator protein 3 (CALHM3)
• Synonyms: Protein A
• Gene Name: CALHM3
• Related Disease: Endometriosis
• UniProt ID: CAHM3_HUMAN
• Pfam ID: PF14798
• Sequence:
  MDKFRMLFQHFQSSSESVMNGICLLLAAVTVKLYSSFDFNCPCLVHYNALYGLGLLLTPP
  LALFLCGLLANRQSVVMVEEWRRPAGHRRKDPGIIRYMCSSVLQRALAAPLVWILLALLD
  GKCFVCAFSSSVDPEKFLDFANMTPSQVQLFLAKVPCKEDELVRDSPARKAVSRYLRCLS
  QAIGWSVTLLLIIAAFLARCLRPCFDQTVFLQRRYWSNYVDLEQKLFDETCCEHARDFAH
  RCVLHFFASMRSELQARGLRRGNAGRRLELPAVPEPPEGLDSGSGKAHLRAISSREQVDR
  LLSTWYSSKPPLDLAASPGLCGGGLSHRAPTLALGTRLSQHTDV
• Function: Pore-forming subunit of a voltage-gated ion channel, also permeable to larger molecules including ATP. Together with CALHM1, forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells (TBCs). CALHM1-CALHM3-mediated ATP released acts as a neurotransmitter to gustatory neurons in response to GPCR-mediated tastes, including sweet, bitter and umami substances.
• Tissue Specificity: Specifically expressed in circumvallate taste bud cells.
• Reactome Pathway:
  Sensory perception of salty taste (R-HSA-9730628)
  Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometriosis	DISX1AG8	moderate	Genetic Variation	[1]

4 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 Calcium homeostasis modulator protein 3 (CALHM3).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Calcium homeostasis modulator protein 3 (CALHM3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Calcium homeostasis modulator protein 3 (CALHM3).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Calcium homeostasis modulator protein 3 (CALHM3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Calcium homeostasis modulator protein 3 (CALHM3).	[4]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Calcium homeostasis modulator protein 3 (CALHM3).	[7]

References

• [1] New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study.Eur J Obstet Gynecol Reprod Biol. 2017 Oct;217:106-112. doi: 10.1016/j.ejogrb.2017.08.037. Epub 2017 Sep 1.
• [2] 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.
• [3] 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.
• [4] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] 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.