Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NXMLV)

• DOT Name: Cardiac-enriched FHL2-interacting protein (C10ORF71)
• Gene Name: C10ORF71
• Related Disease: Alzheimer disease
• UniProt ID: CEFIP_HUMAN
• Pfam ID: PF15232
• Sequence:
  MMQGNKKCTDAFSDSSSIGSVLDDADREVSSLTDRAFRSLCISEDTSFHDSYLAVSPDIT
  RQVFGTFHQRTVGHTQRKSGIWSQLPSQGTEHSGWAATFQQLPKYVQGEEKYPKTSPPPT
  PVQRRLEVPVSGLRSSNKPVSKVSTLIKSFDRTESQRCESRPTASKPPALKNPPKFAPLP
  ENSVNFCFDSAFLTVRRVPAEVSNTHQNSYQPGRKHGEQESSKNPEMACHGSSSFLPAAN
  DTATLCESKFPSPHHKPVTGEPGRGKGTFLHSENSAFESWNAHQPKLLERKDTAGTVPES
  KAPKHYGDTTLLREPCPPERTVSPCQVQASCSQEENRLAAGALSTSIPWGCRDPGAQVFA
  VEGKAPSSQPDSQEKPAQPPWRKPKTGKKGKESLQDTLEEKTQTNQRGPPLYTKHNPQEQ
  FSENNALDLPVEPNEHYDPPFNISKLLTPIIPSKHALDSADSQPAERTPSPPGQLNGYQE
  KEPSECQSRDSYKSKAPSLLFNLKDVRKRVKSTYSSSPLLKVLDEKTRGKVDGKQEPVSN
  GVILPNGLEESPPNELSKERPADDPTASHINPQKDPTADPSEPSADSYLTLSTAPTIAKA
  PFYVNGEAAERSSYENKEVEGELEMGPAGSSWCPDSREHRPRKHLSLRLCNRDPEPGGAT
  EKMKTHQLENGLSRSVSQETEPEREAGLQNTHLNQKFFPGPLSPEEEDVFYSDSQSDFMP
  SLKGKAKFSTSSSDQSFASFDDQQKMWFTENQREDRRKDVSAGDSQKDEKENVMRKDELQ
  YCALSNGHACLENRSQGEALQRERESVSGGRTRKASAEEANFRGSWIGENKGTTFSQAKD
  LTPSPSSASNRHMLFTIKDNTLRATPVIKPIMLPLLRTMSLEDSLSSGHKEEELPRPEWG
  EDPGFCAPENQDILGTSTPTNTRGTRVKCMANEVMEDPGQGSSMARMEASQPAPKGNFPS
  MPLVGEGDRVKAPPDAAPGLVASNCKSGSADSGKLAAPWHIPTIALPEGDIEDQPPPWQP
  ENCWEEQTPGFKSHFLSTPRAGPPGRRLVPSERANSPNPGSPGESSACSPAASNIWEESS
  QAPGGPELLPEEPNQASPWASSSPARVTRREDLTHALVWEGGSDPLLELSAEDLRTLSPR
  GSLLDVATSPAGTSGRLELPAQLERTASKPPAVPPKTEKALRRAKKLASKRRKTDQAQEK
  HGESQEGKPCPEDLEQTQQRPLCPRERPRHNFPVVRSLPPPVHRHSVSGFSEPVGRRPGG
  PQSLTPLPAYPATQKVLQDPQSGEYFVFDLPLQVKIKTFYDPETGKYVKVSIPSSEGASP
  EPPPPDALAAPYVLYPGFQPVPVTALMPLRCSSQLSAPTFLRQGPRASAARARTQSVHES
  GLQLDPGPHGDCTPHSAGQRPHGPPQSPGEEGVEAPGLGIISTDDLEDFATEGIS
• Function: Plays an important role in cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway.
• Tissue Specificity: Expressed in the heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]

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 Cardiac-enriched FHL2-interacting protein (C10ORF71).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cardiac-enriched FHL2-interacting protein (C10ORF71).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cardiac-enriched FHL2-interacting protein (C10ORF71).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cardiac-enriched FHL2-interacting protein (C10ORF71).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cardiac-enriched FHL2-interacting protein (C10ORF71).	[6]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [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] 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.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.