Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTANX32T)

• DOT Name: Uncharacterized protein KIAA0825 (KIAA0825)
• Gene Name: KIAA0825
• Related Disease:
  Advanced cancer
  Polydactyly, postaxial, type a10
  Postaxial polydactyly
  Postaxial polydactyly type A
  Diabetic retinopathy
• UniProt ID: K0825_HUMAN
• Pfam ID: PF14906
• Sequence:
  MDWDDEYSHNSFDLHCLLNSFPGDLEFEQIFSDIDEKIEQNAASIKHCIKEIQSEINKQC
  PGVQLQTTTDCFEWLTNYNYSTSESSFISHGDLIKFFKTLQDLLKNEQNQEEMTLDLLWD
  LSCHSSVSFPSTLSGTSFHFLSRTSLHSVEDNSSMDVKSMWDDIRLHLRRFLVSKLQSHN
  EINNSQQKILLKKQCLQQLLFLYPESEVIIKYQNIQNKLLANLLWNCFPSYNRDSNLDVI
  AHGYQSTMLKLYSVIKEDFNTLCEILAPSSMVKFIKETYLDTVTEEMAKFLENFCELQFR
  ENAVRVVKTSKSSSKHRGAVHALVTTECPQKGRNFSLPLDKVEFLSQLIKSFMKLEKGVQ
  ELFDEILLSLKITRDTSGILEKSDREVVMEKPRANETNIPSEQSLPGKEATLLDFGWRSA
  FKEVSLPMAHCVVTAIEGFSTKILQQEQNERSSAVSYAMNLVNVQQVWQDSHMFPEEEQP
  KKIGKFCSDIMEKLDTMLPLALACRDDSFQEIRANLVEACCKVATAVLQRLQERAKEVPS
  KAPLKNLHTYLSTAVYVFQHFKRYDNLMKEMTKKPIFLVLVQRYQEFINTLQFQVTNYCV
  RVCATSILQDAESHHWDDYKAFYEGERCSFSIQMWHYFCWSLHYDLWTILPPKLAQEILV
  EVLEKSLSLLASRYARAHPSRKRTPQLRLDVTTILICTENMLWSVCTSVQKLLNPHQHTD
  DKIFKIHTHCNNLFTTLVILTSPLTELYKTFQHGLDESASDSLKSFFKQPLYWVSCISHF
  YPSLLRTPSAGGLKAEGQLKLLLSQPRCNWNLLLETLLHHDGLLLRILLKSSKQVSDTEN
  NLNQGPSLMEAIFKILYHCSFSPQTFANVFVSYMEEEQLWDFLYNIPVSTCVEYELEVIR
  CLRLALTDAIKDTVQQIVSVMSSRRNCETNLNKHIVPDCLLESMPKEWNYSPKETNRKES
  CKSFTRLTAQAVSIVISKLPTVIACLPPPVKYFFFLSERKMSKKFVELKKAGLLVWNLIV
  IICRIFEDGNTVELLTGASLDRWSKEKLGLICMCLKSIMGDQTSIHNQMIQKVIQSIEQQ
  KPNWIERQLLKARKLSTECAFMTIEKSTALQEGDVALELTEQKINTMVLDLCHKPGGREY
  LRQIYHIMQLNEEYLKEQLFSMNSSEEKPLPIRPLKTTLRSIEDQPSAFNPFHVYKAFSE
  NMLDQSAITKWNWNWAKLLPNYLRLDKMTFSVLLKNRWEMKKDETLEEEEKAILEHLKQI
  CTPQNSSASDNIEEQ

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Polydactyly, postaxial, type a10	DISI49GW	Strong	Autosomal recessive	[2]
Postaxial polydactyly	DIS085OV	Strong	Genetic Variation	[3]
Postaxial polydactyly type A	DIS4IIPW	Supportive	Autosomal recessive	[3]
Diabetic retinopathy	DISHGUJM	Limited	Genetic Variation	[4]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Uncharacterized protein KIAA0825 (KIAA0825).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Uncharacterized protein KIAA0825 (KIAA0825).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Uncharacterized protein KIAA0825 (KIAA0825).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Uncharacterized protein KIAA0825 (KIAA0825).	[12]

5 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 Uncharacterized protein KIAA0825 (KIAA0825).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Uncharacterized protein KIAA0825 (KIAA0825).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Uncharacterized protein KIAA0825 (KIAA0825).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Uncharacterized protein KIAA0825 (KIAA0825).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Uncharacterized protein KIAA0825 (KIAA0825).	[13]

References

• [1] Cancer risk susceptibility loci in a Swedish population.Oncotarget. 2017 Nov 25;8(66):110300-110310. doi: 10.18632/oncotarget.22687. eCollection 2017 Dec 15.
• [2] Estrogen-related receptor gamma implicated in a phenotype including hearing loss and mild developmental delay. Eur J Hum Genet. 2016 Nov;24(11):1622-1626. doi: 10.1038/ejhg.2016.64. Epub 2016 Jul 6.
• [3] Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly. Hum Genet. 2019 Jun;138(6):593-600. doi: 10.1007/s00439-019-02000-0. Epub 2019 Apr 13.
• [4] Genome-wide association study of diabetic retinopathy in a Taiwanese population.Ophthalmology. 2011 Apr;118(4):642-8. doi: 10.1016/j.ophtha.2010.07.020. Epub 2011 Feb 18.
• [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] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [12] 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.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.