Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT90S9W6)

• DOT Name: Pecanex-like protein 2 (PCNX2)
• Synonyms: Pecanex homolog protein 2
• Gene Name: PCNX2
• Related Disease:
  Differentiated thyroid carcinoma
  Thyroid gland papillary carcinoma
  Absence epilepsy
  Non-insulin dependent diabetes
  Colorectal neoplasm
  Thyroid gland carcinoma
• UniProt ID: PCX2_HUMAN
• Pfam ID: PF05041
• Sequence:
  MVSQVLQLLRQGVWAALTGGWYHDPEQSKFTNSCHLYLWLFLLLLPLALHLAFPPNAIIV
  FFYCSAVTIFFTIIKLVSYRLHLMFDKGEVIQQKPSRKEEKPNKDKEAKGEHITNHRNPS
  NNRQIHNGKKEEASRNLSTPPLRCSSRGQSITSHHSSGPLELSAQETVEDLKGVILLEDH
  PIAPVSSTSPGIKVESLPASQAHMLETTTKSVIPVKPVATETLINGKGKERGGKGQPPLR
  HRSEGGLVDKGPLKKLPHLSLSQYDLLETDVSFQPWGSENSVLIPEPVSCPRGSIRERVQ
  SKSPQDSLSSSCPQCDTIVAKPVEEPADTSCQVDTSCQGDLPLHQEVDSSDSEVAVTLID
  TSQPGDPLSLHEPIKIVITMSSTPNSMTDLESSLHLRVVGTEKTSVKSDAEPTNPGAAGS
  PNAEQISIPVITLDLPEGGGGGVPCPEGNGSERTPERLKTRVSTNQCSGYGSGEGGNAIK
  DHSSSSREPWESVSRLTPDTGSESKVGKEGQTNLDPSSCKSSHEKRHARVLSVDSGTDVF
  LSKSSAEIVNDTEKTMPTSKSDLEAKEGQMPNESNFLEFVSLLESINTSKMTASSQLNGS
  AEQNEESGLLRDNCSQEKKEEILENEKPSGHSSKQGKPDLQSQDHTSTGPACTQPAKTTA
  FFQGNRQRQIIYRVTSQQDSSVLQVISGPETSVQEEISVDAMHVFIDEHGEIRSCYLKSG
  NQKEGPLQPLPSNNDCLSQAREMQVSSSSTTTSESQDPSSGDPAVSALQQQLLLMVARRT
  QSETPRHVSQDLEASSCSSTQGKFNREQFYKFIIFPGKWIKVWYDRLTLLALLDRTEDIK
  ENVLAILLIVLVSLLGFLTLSQGFCKDMWVLLFCLVMASCQYSLLKSVQPDPASPIHGHN
  QIITYSRPIYFCVLCGLILLLDTGAKARHPPSYVVYGLKLFSPVFLQSARDYLIVFLYCF
  PAISLLGLFPQINTFCTYLLEQIDMLFFGGSAVSGITSAVYSVARSVLAAALLHAVCFSA
  VKEPWSMQHIPALFSAFCGLLVALSYHLSRQSSDPSVLMSFIQCRLFPKFLHQNLAESAA
  DPLPKKMKDSVTDVLKWDLIVCAVVAVLSFAVSASTVFLSLRPFLSIVLFALAGAVGFVT
  HYVLPQLRKHHPWMWISHPILKNKEYHQREVRDVAHLMWFERLYVWLQCFEKYILYPALI
  LNALTIDAFLISNHRRLGTHWDIFLMIIAGMKLLRTSFCNPVYQFINLSFTVIFFHFDYK
  DISESFLLDFFMVSILFSKLGDLLHKLQFVLTYVAPWQMAWGSSFHVFAQLFAIPHSAML
  FFQTIATSIFSTPLSPFLGSVIFITSYVRPVKFWEKNYNTRRVDNSNTRLAVQIERDPGN
  DDNNLNSIFYEHLTRTLQESLCGDLVLGRWGNYSSGDCFILASDDLNAFVHLIEIGNGLV
  TFQLRGLEFRGTYCQQREVEAIMEGDEEDRGCCCCKPGHLPHLLSCNAAFHLRWLTWEIT
  QTQYILEGYSILDNNAATMLQVFDLRRILIRYYIKSIIYYMVTSPKLLSWIKNESLLKSL
  QPFAKWHYIERDLAMFNINIDDDYVPCLQGITRASFCNVYLEWIQHCARKRQEPSTTLDS
  DEDSPLVTLSFALCTLGRRALGTAAHNMAISLDSFLYGLHVLFKGDFRITARDEWVFADM
  DLLHKVVAPAIRMSLKLHQDQFTCPDEYEDPAVLYEAIQSFEKKVVICHEGDPAWRGAVL
  SNKEELLTLRHVVDEGADEYKVIMLHRSFLSFKVIKVNKECVRGLWAGQQQELIFLRNRN
  PERGSIQNNKQVLRNLINSSCDQPLGYPMYVSPLTTSYLGTHRQLKNIWGGPITLDRIRT
  WFWTKWVRMRKDCNARQHSGGNIEDVDGGGAPTTGGNNAPSGGSQESSAEQPRKGGAQHG
  VSSCEGTQRTGRRKGRSQSVQAHSALSQRPPMLSSSGPILESRQTFLQTSTSVHELAQRL
  SGSRLSLHASATSLHSQPPPVTTTGHLSVRERAEALIRSSLGSSTSSTLSFLFGKRSFSS
  ALVISGLSAAEGGNTSDTQSSSSVNIVMGPSARAASQATRHLSEPCEPPDATEQGQLHDR
  CLAEAVADTLGVVCRRASQEDMGLDDTASQQSVSDEQ
• Function: May play a role in tumorigenesis of colorectal carcinomas with high microsatellite instability (MSI-H).

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Differentiated thyroid carcinoma	DIS1V20Y	Definitive	Genetic Variation	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Genetic Variation	[1]
Absence epilepsy	DISJPOUD	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Colorectal neoplasm	DISR1UCN	Limited	Biomarker	[4]
Thyroid gland carcinoma	DISMNGZ0	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Pecanex-like protein 2 (PCNX2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pecanex-like protein 2 (PCNX2).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Pecanex-like protein 2 (PCNX2).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Pecanex-like protein 2 (PCNX2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pecanex-like protein 2 (PCNX2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Pecanex-like protein 2 (PCNX2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pecanex-like protein 2 (PCNX2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Pecanex-like protein 2 (PCNX2).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Pecanex-like protein 2 (PCNX2).	[13]

References

• [1] Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer.Nat Commun. 2017 Jul 13;8:15966. doi: 10.1038/ncomms15966.
• [2] Unraveling genetic modifiers in the gria4 mouse model of absence epilepsy.PLoS Genet. 2014 Jul 10;10(7):e1004454. doi: 10.1371/journal.pgen.1004454. eCollection 2014 Jul.
• [3] Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.PLoS Genet. 2011 Apr;7(4):e1001363. doi: 10.1371/journal.pgen.1001363. Epub 2011 Apr 7.
• [4] Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability.Oncogene. 2002 Aug 1;21(33):5081-7. doi: 10.1038/sj.onc.1205703.
• [5] A genome-wide association study yields five novel thyroid cancer risk loci.Nat Commun. 2017 Feb 14;8:14517. doi: 10.1038/ncomms14517.
• [6] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [7] 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.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] 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.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [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] 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.