Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6X9V5)

• DOT Name: FERM domain-containing protein 6 (FRMD6)
• Synonyms: Willin
• Gene Name: FRMD6
• Related Disease:
  Hepatocellular carcinoma
  Alzheimer disease
  Asthma
• UniProt ID: FRMD6_HUMAN
• Pfam ID: PF09380 ; PF00373 ; PF09379
• Sequence:
  MNKLNFHNNRVMQDRRSVCIFLPNDESLNIIINVKILCHQLLVQVCDLLRLKDCHLFGLS
  VIQNNEHVYMELSQKLYKYCPKEWKKEASKVRQYEVTWGIDQFGPPMIIHFRVQYYVENG
  RLISDRAARYYYYWHLRKQVLHSQCVLREEAYFLLAAFALQADLGNFKRNKHYGKYFEPE
  AYFPSWVVSKRGKDYILKHIPNMHKDQFALTASEAHLKYIKEAVRLDDVAVHYYRLYKDK
  REIEASLTLGLTMRGIQIFQNLDEEKQLLYDFPWTNVGKLVFVGKKFEILPDGLPSARKL
  IYYTGCPMRSRHLLQLLSNSHRLYMNLQPVLRHIRKLEENEEKKQYRESYISDNLDLDMD
  QLEKRSRASGSSAGSMKHKRLSRHSTASHSSSHTSGIEADTKPRDTGPEDSYSSSAIHRK
  LKTCSSMTSHGSSHTSGVESGGKDRLEEDLQDDEIEMLVDDPRDLEQMNEESLEVSPDMC
  IYITEDMLMSRKLNGHSGLIVKEIGSSTSSSSETVVKLRGQSTDSLPQTICRKPKTSTDR
  HSLSLDDIRLYQKDFLRIAGLCQDTAQSYTFGCGHELDEEGLYCNSCLAQQCINIQDAFP
  VKRTSKYFSLDLTHDEVPEFVV
• KEGG Pathway:
  Hippo sig.ling pathway (hsa04390)
  Hippo sig.ling pathway - multiple species (hsa04392)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Asthma	DISW9QNS	Limited	Biomarker	[3]

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 FERM domain-containing protein 6 (FRMD6).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of FERM domain-containing protein 6 (FRMD6).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of FERM domain-containing protein 6 (FRMD6).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of FERM domain-containing protein 6 (FRMD6).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of FERM domain-containing protein 6 (FRMD6).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of FERM domain-containing protein 6 (FRMD6).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of FERM domain-containing protein 6 (FRMD6).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FERM domain-containing protein 6 (FRMD6).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of FERM domain-containing protein 6 (FRMD6).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of FERM domain-containing protein 6 (FRMD6).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of FERM domain-containing protein 6 (FRMD6).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of FERM domain-containing protein 6 (FRMD6).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of FERM domain-containing protein 6 (FRMD6).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of FERM domain-containing protein 6 (FRMD6).	[17]

References

• [1] MTA2 promotes HCC progression through repressing FRMD6, a key upstream component of hippo signaling pathway.Biochem Biophys Res Commun. 2019 Jul 12;515(1):112-118. doi: 10.1016/j.bbrc.2019.05.025. Epub 2019 May 22.
• [2] Genome-wide and gene-based association implicates FRMD6 in Alzheimer disease.Hum Mutat. 2012 Mar;33(3):521-9. doi: 10.1002/humu.22009. Epub 2012 Jan 23.
• [3] Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy.Allergy Asthma Immunol Res. 2017 May;9(3):247-256. doi: 10.4168/aair.2017.9.3.247.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] 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.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.