Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLX9B4Y)

• DOT Name: Calcium homeostasis modulator protein 6 (CALHM6)
• Synonyms: Protein FAM26F
• Gene Name: CALHM6
• Related Disease:
  Immunodeficiency
  Neoplasm
  Ulcerative colitis
  Rheumatoid arthritis
• UniProt ID: CAHM6_HUMAN
• PDB ID: 6YTV; 6YTX
• Pfam ID: PF14798
• Sequence:
  MEKFRAVLDLHVKHHSALGYGLVTLLTAGGERIFSAVAFQCPCSAAWNLPYGLVFLLVPA
  LALFLLGYVLSARTWRLLTGCCSSARASCGSALRGSLVCTQISAAAALAPLTWVAVALLG
  GAFYECAATGSAAFAQRLCLGRNRSCAAELPLVPCNQAKASDVQDLLKDLKAQSQVLGWI
  LIAVVIIILLIFTSVTRCLSPVSFLQLKFWKIYLEQEQQILKSKATEHATELAKENIKCF
  FEGSHPKEYNTPSMKEWQQISSLYTFNPKGQYYSMLHKYVNRKEKTHSIRSTEGDTVIPV
  LGFVDSSGINSTPEL
• Function: Pore-forming subunit of a voltage-gated ion channel.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency	DIS093I0	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[3]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[4]

1 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 6 (CALHM6).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Calcium homeostasis modulator protein 6 (CALHM6).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Calcium homeostasis modulator protein 6 (CALHM6).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Calcium homeostasis modulator protein 6 (CALHM6).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Calcium homeostasis modulator protein 6 (CALHM6).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Calcium homeostasis modulator protein 6 (CALHM6).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Calcium homeostasis modulator protein 6 (CALHM6).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Calcium homeostasis modulator protein 6 (CALHM6).	[11]

References

• [1] Pre-infection transcript levels of FAM26F in peripheral blood mononuclear cells inform about overall plasma viral load in acute and post-acute phase after simian immunodeficiency virus infection.J Gen Virol. 2016 Dec;97(12):3400-3412. doi: 10.1099/jgv.0.000632. Epub 2016 Oct 18.
• [2] Structural and functional annotation of human FAM26F: A multifaceted protein having a critical role in the immune system.Gene. 2017 Jan 15;597:66-75. doi: 10.1016/j.gene.2016.10.029. Epub 2016 Oct 23.
• [3] A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.Hum Mol Genet. 2014 Dec 20;23(25):6927-34. doi: 10.1093/hmg/ddu398. Epub 2014 Jul 31.
• [4] Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids.Clin Exp Rheumatol. 2016 Jul-Aug;34(4):685-9. Epub 2016 Jun 22.
• [5] 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.
• [6] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [10] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.