Details of Drug Off-Target (DOT)

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

• DOT Name: E3 ubiquitin-protein ligase HERC2 (HERC2)
• Synonyms: EC 2.3.2.26; HECT domain and RCC1-like domain-containing protein 2; HECT-type E3 ubiquitin transferase HERC2
• Gene Name: HERC2
• Related Disease:
  T lymphoblastic leukaemia
  Type-1 diabetes
  Advanced cancer
  Alzheimer disease
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Crohn disease
  Developmental delay with autism spectrum disorder and gait instability
  Intellectual disability
  Melanoma
  Myopia
  Neurodevelopmental disorder
  Non-small-cell lung cancer
  Ocular albinism
  Oculocutaneous albinism
  Oculocutaneous albinism type 2
  Pervasive developmental disorder
  Refractive error
  Squamous cell carcinoma
  Ulcerative colitis
  Vitiligo
  Xeroderma pigmentosum
  Angelman syndrome
  Breast neoplasm
  Glaucoma/ocular hypertension
  Neuroblastoma
  Asthma
  Basal cell carcinoma
  Basal cell neoplasm
  Cutaneous squamous cell carcinoma
  Skin cancer
• UniProt ID: HERC2_HUMAN
• PDB ID: 2KEO; 3KCI; 4L1M; 6WW3; 6WW4; 7Q40; 7Q41; 7Q42; 7Q43; 7Q44; 7Q45; 7Q46; 7RGW
• EC Number: 2.3.2.26
• Pfam ID: PF03256 ; PF11515 ; PF00173 ; PF00632 ; PF06701 ; PF00415 ; PF00569
• Sequence:
  MPSESFCLAAQARLDSKWLKTDIQLAFTRDGLCGLWNEMVKDGEIVYTGTESTQNGELPP
  RKDDSVEPSGTKKEDLNDKEKKDEEETPAPIYRAKSILDSWVWGKQPDVNELKECLSVLV
  KEQQALAVQSATTTLSALRLKQRLVILERYFIALNRTVFQENVKVKWKSSGISLPPVDKK
  SSRPAGKGVEGLARVGSRAALSFAFAFLRRAWRSGEDADLCSELLQESLDALRALPEASL
  FDESTVSSVWLEVVERATRFLRSVVTGDVHGTPATKGPGSIPLQDQHLALAILLELAVQR
  GTLSQMLSAILLLLQLWDSGAQETDNERSAQGTSAPLLPLLQRFQSIICRKDAPHSEGDM
  HLLSGPLSPNESFLRYLTLPQDNELAIDLRQTAVVVMAHLDRLATPCMPPLCSSPTSHKG
  SLQEVIGWGLIGWKYYANVIGPIQCEGLANLGVTQIACAEKRFLILSRNGRVYTQAYNSD
  TLAPQLVQGLASRNIVKIAAHSDGHHYLALAATGEVYSWGCGDGGRLGHGDTVPLEEPKV
  ISAFSGKQAGKHVVHIACGSTYSAAITAEGELYTWGRGNYGRLGHGSSEDEAIPMLVAGL
  KGLKVIDVACGSGDAQTLAVTENGQVWSWGDGDYGKLGRGGSDGCKTPKLIEKLQDLDVV
  KVRCGSQFSIALTKDGQVYSWGKGDNQRLGHGTEEHVRYPKLLEGLQGKKVIDVAAGSTH
  CLALTEDSEVHSWGSNDQCQHFDTLRVTKPEPAALPGLDTKHIVGIACGPAQSFAWSSCS
  EWSIGLRVPFVVDICSMTFEQLDLLLRQVSEGMDGSADWPPPQEKECVAVATLNLLRLQL
  HAAISHQVDPEFLGLGLGSILLNSLKQTVVTLASSAGVLSTVQSAAQAVLQSGWSVLLPT
  AEERARALSALLPCAVSGNEVNISPGRRFMIDLLVGSLMADGGLESALHAAITAEIQDIE
  AKKEAQKEKEIDEQEANASTFHRSRTPLDKDLINTGICESSGKQCLPLVQLIQQLLRNIA
  SQTVARLKDVARRISSCLDFEQHSRERSASLDLLLRFQRLLISKLYPGESIGQTSDISSP
  ELMGVGSLLKKYTALLCTHIGDILPVAASIASTSWRHFAEVAYIVEGDFTGVLLPELVVS
  IVLLLSKNAGLMQEAGAVPLLGGLLEHLDRFNHLAPGKERDDHEELAWPGIMESFFTGQN
  CRNNEEVTLIRKADLENHNKDGGFWTVIDGKVYDIKDFQTQSLTGNSILAQFAGEDPVVA
  LEAALQFEDTRESMHAFCVGQYLEPDQEIVTIPDLGSLSSPLIDTERNLGLLLGLHASYL
  AMSTPLSPVEIECAKWLQSSIFSGGLQTSQIHYSYNEEKDEDHCSSPGGTPASKSRLCSH
  RRALGDHSQAFLQAIADNNIQDHNVKDFLCQIERYCRQCHLTTPIMFPPEHPVEEVGRLL
  LCCLLKHEDLGHVALSLVHAGALGIEQVKHRTLPKSVVDVCRVVYQAKCSLIKTHQEQGR
  SYKEVCAPVIERLRFLFNELRPAVCNDLSIMSKFKLLSSLPRWRRIAQKIIRERRKKRVP
  KKPESTDDEEKIGNEESDLEEACILPHSPINVDKRPIAIKSPKDKWQPLLSTVTGVHKYK
  WLKQNVQGLYPQSPLLSTIAEFALKEEPVDVEKMRKCLLKQLERAEVRLEGIDTILKLAS
  KNFLLPSVQYAMFCGWQRLIPEGIDIGEPLTDCLKDVDLIPPFNRMLLEVTFGKLYAWAV
  QNIRNVLMDASAKFKELGIQPVPLQTITNENPSGPSLGTIPQARFLLVMLSMLTLQHGAN
  NLDLLLNSGMLALTQTALRLIGPSCDNVEEDMNASAQGASATVLEETRKETAPVQLPVSG
  PELAAMMKIGTRVMRGVDWKWGDQDGPPPGLGRVIGELGEDGWIRVQWDTGSTNSYRMGK
  EGKYDLKLAELPAAAQPSAEDSDTEDDSEAEQTERNIHPTAMMFTSTINLLQTLCLSAGV
  HAEIMQSEATKTLCGLLRMLVESGTTDKTSSPNRLVYREQHRSWCTLGFVRSIALTPQVC
  GALSSPQWITLLMKVVEGHAPFTATSLQRQILAVHLLQAVLPSWDKTERARDMKCLVEKL
  FDFLGSLLTTCSSDVPLLRESTLRRRRVRPQASLTATHSSTLAEEVVALLRTLHSLTQWN
  GLINKYINSQLRSITHSFVGRPSEGAQLEDYFPDSENPEVGGLMAVLAVIGGIDGRLRLG
  GQVMHDEFGEGTVTRITPKGKITVQFSDMRTCRVCPLNQLKPLPAVAFNVNNLPFTEPML
  SVWAQLVNLAGSKLEKHKIKKSTKQAFAGQVDLDLLRCQQLKLYILKAGRALLSHQDKLR
  QILSQPAVQETGTVHTDDGAVVSPDLGDMSPEGPQPPMILLQQLLASATQPSPVKAIFDK
  QELEAAALAVCQCLAVESTHPSSPGFEDCSSSEATTPVAVQHIRPARVKRRKQSPVPALP
  IVVQLMEMGFSRRNIEFALKSLTGASGNASSLPGVEALVGWLLDHSDIQVTELSDADTVS
  DEYSDEEVVEDVDDAAYSMSTGAVVTESQTYKKRADFLSNDDYAVYVRENIQVGMMVRCC
  RAYEEVCEGDVGKVIKLDRDGLHDLNVQCDWQQKGGTYWVRYIHVELIGYPPPSSSSHIK
  IGDKVRVKASVTTPKYKWGSVTHQSVGVVKAFSANGKDIIVDFPQQSHWTGLLSEMELVP
  SIHPGVTCDGCQMFPINGSRFKCRNCDDFDFCETCFKTKKHNTRHTFGRINEPGQSAVFC
  GRSGKQLKRCHSSQPGMLLDSWSRMVKSLNVSSSVNQASRLIDGSEPCWQSSGSQGKHWI
  RLEIFPDVLVHRLKMIVDPADSSYMPSLVVVSGGNSLNNLIELKTININPSDTTVPLLND
  CTEYHRYIEIAIKQCRSSGIDCKIHGLILLGRIRAEEEDLAAVPFLASDNEEEEDEKGNS
  GSLIRKKAAGLESAATIRTKVFVWGLNDKDQLGGLKGSKIKVPSFSETLSALNVVQVAGG
  SKSLFAVTVEGKVYACGEATNGRLGLGISSGTVPIPRQITALSSYVVKKVAVHSGGRHAT
  ALTVDGKVFSWGEGDDGKLGHFSRMNCDKPRLIEALKTKRIRDIACGSSHSAALTSSGEL
  YTWGLGEYGRLGHGDNTTQLKPKMVKVLLGHRVIQVACGSRDAQTLALTDEGLVFSWGDG
  DFGKLGRGGSEGCNIPQNIERLNGQGVCQIECGAQFSLALTKSGVVWTWGKGDYFRLGHG
  SDVHVRKPQVVEGLRGKKIVHVAVGALHCLAVTDSGQVYAWGDNDHGQQGNGTTTVNRKP
  TLVQGLEGQKITRVACGSSHSVAWTTVDVATPSVHEPVLFQTARDPLGASYLGVPSDADS
  SAASNKISGASNSKPNRPSLAKILLSLDGNLAKQQALSHILTALQIMYARDAVVGALMPA
  AMIAPVECPSFSSAAPSDASAMASPMNGEECMLAVDIEDRLSPNPWQEKREIVSSEDAVT
  PSAVTPSAPSASARPFIPVTDDLGAASIIAETMTKTKEDVESQNKAAGPEPQALDEFTSL
  LIADDTRVVVDLLKLSVCSRAGDRGRDVLSAVLSGMGTAYPQVADMLLELCVTELEDVAT
  DSQSGRLSSQPVVVESSHPYTDDTSTSGTVKIPGAEGLRVEFDRQCSTERRHDPLTVMDG
  VNRIVSVRSGREWSDWSSELRIPGDELKWKFISDGSVNGWGWRFTVYPIMPAAGPKELLS
  DRCVLSCPSMDLVTCLLDFRLNLASNRSIVPRLAASLAACAQLSALAASHRMWALQRLRK
  LLTTEFGQSININRLLGENDGETRALSFTGSALAALVKGLPEALQRQFEYEDPIVRGGKQ
  LLHSPFFKVLVALACDLELDTLPCCAETHKWAWFRRYCMASRVAVALDKRTPLPRLFLDE
  VAKKIRELMADSENMDVLHESHDIFKREQDEQLVQWMNRRPDDWTLSAGGSGTIYGWGHN
  HRGQLGGIEGAKVKVPTPCEALATLRPVQLIGGEQTLFAVTADGKLYATGYGAGGRLGIG
  GTESVSTPTLLESIQHVFIKKVAVNSGGKHCLALSSEGEVYSWGEAEDGKLGHGNRSPCD
  RPRVIESLRGIEVVDVAAGGAHSACVTAAGDLYTWGKGRYGRLGHSDSEDQLKPKLVEAL
  QGHRVVDIACGSGDAQTLCLTDDDTVWSWGDGDYGKLGRGGSDGCKVPMKIDSLTGLGVV
  KVECGSQFSVALTKSGAVYTWGKGDYHRLGHGSDDHVRRPRQVQGLQGKKVIAIATGSLH
  CVCCTEDGEVYTWGDNDEGQLGDGTTNAIQRPRLVAALQGKKVNRVACGSAHTLAWSTSK
  PASAGKLPAQVPMEYNHLQEIPIIALRNRLLLLHHLSELFCPCIPMFDLEGSLDETGLGP
  SVGFDTLRGILISQGKEAAFRKVVQATMVRDRQHGPVVELNRIQVKRSRSKGGLAGPDGT
  KSVFGQMCAKMSSFGPDSLLLPHRVWKVKFVGESVDDCGGGYSESIAEICEELQNGLTPL
  LIVTPNGRDESGANRDCYLLSPAARAPVHSSMFRFLGVLLGIAIRTGSPLSLNLAEPVWK
  QLAGMSLTIADLSEVDKDFIPGLMYIRDNEATSEEFEAMSLPFTVPSASGQDIQLSSKHT
  HITLDNRAEYVRLAINYRLHEFDEQVAAVREGMARVVPVPLLSLFTGYELETMVCGSPDI
  PLHLLKSVATYKGIEPSASLIQWFWEVMESFSNTERSLFLRFVWGRTRLPRTIADFRGRD
  FVIQVLDKYNPPDHFLPESYTCFFLLKLPRYSCKQVLEEKLKYAIHFCKSIDTDDYARIA
  LTGEPAADDSSDDSDNEDVDSFASDSTQDYLTGH
• Function: E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway. Modulates also iron metabolism by regulating the basal turnover of FBXL5.
• KEGG Pathway: Ubiquitin mediated proteolysis (hsa04120)
• Reactome Pathway:
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  Nonhomologous End-Joining (NHEJ) (R-HSA-5693571)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  G2/M DNA damage checkpoint (R-HSA-69473)
  Antigen processing (R-HSA-983168)
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T lymphoblastic leukaemia	DIS2PNPP	Definitive	Genetic Variation	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[7]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[7]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[7]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[7]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[2]
Developmental delay with autism spectrum disorder and gait instability	DISGM81U	Strong	Autosomal recessive	[8]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[9]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[10]
Myopia	DISK5S60	Strong	Biomarker	[11]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[12]
Ocular albinism	DIS5IHK1	Strong	Genetic Variation	[13]
Oculocutaneous albinism	DISJS7CU	Strong	Biomarker	[14]
Oculocutaneous albinism type 2	DISMTYMP	Strong	Biomarker	[15]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[5]
Refractive error	DISWNEQ1	Strong	Biomarker	[11]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[16]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[2]
Vitiligo	DISR05SL	Strong	Genetic Variation	[17]
Xeroderma pigmentosum	DISQ9H19	Strong	Genetic Variation	[18]
Angelman syndrome	DIS4QVXO	moderate	Genetic Variation	[19]
Breast neoplasm	DISNGJLM	moderate	CausalMutation	[20]
Glaucoma/ocular hypertension	DISLBXBY	moderate	Genetic Variation	[21]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[22]
Asthma	DISW9QNS	Limited	Genetic Variation	[23]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[24]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[24]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Genetic Variation	[14]
Skin cancer	DISTM18U	Limited	Genetic Variation	[14]

8 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 E3 ubiquitin-protein ligase HERC2 (HERC2).	[25]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of E3 ubiquitin-protein ligase HERC2 (HERC2).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of E3 ubiquitin-protein ligase HERC2 (HERC2).	[28]
Menadione	DMSJDTY	Approved	Menadione affects the expression of E3 ubiquitin-protein ligase HERC2 (HERC2).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of E3 ubiquitin-protein ligase HERC2 (HERC2).	[30]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of E3 ubiquitin-protein ligase HERC2 (HERC2).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of E3 ubiquitin-protein ligase HERC2 (HERC2).	[33]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of E3 ubiquitin-protein ligase HERC2 (HERC2).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of E3 ubiquitin-protein ligase HERC2 (HERC2).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of E3 ubiquitin-protein ligase HERC2 (HERC2).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of E3 ubiquitin-protein ligase HERC2 (HERC2).	[32]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of E3 ubiquitin-protein ligase HERC2 (HERC2).	[35]

References

• [1] SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia.Blood Cancer J. 2018 Jan 19;8(1):11. doi: 10.1038/s41408-017-0036-5.
• [2] Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects.Hum Mol Genet. 2010 May 15;19(10):2059-67. doi: 10.1093/hmg/ddq078. Epub 2010 Feb 22.
• [3] HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA.Cancer Res. 2018 Nov 15;78(22):6371-6385. doi: 10.1158/0008-5472.CAN-18-1877. Epub 2018 Oct 2.
• [4] 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.
• [5] A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder. Hum Mutat. 2012 Dec;33(12):1639-46. doi: 10.1002/humu.22237.
• [6] Splice variants and expression patterns of SHEP1, BCAR3 and NSP1, a gene family involved in integrin and receptor tyrosine kinase signaling.Gene. 2007 Apr 15;391(1-2):161-70. doi: 10.1016/j.gene.2006.12.016. Epub 2007 Jan 8.
• [7] Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas.Oncotarget. 2017 Oct 9;8(58):98623-98634. doi: 10.18632/oncotarget.21697. eCollection 2017 Nov 17.
• [8] Novel loss-of-function mutation in HERC2 is associated with severe developmental delay and paediatric lethality. J Med Genet. 2021 May;58(5):334-341. doi: 10.1136/jmedgenet-2020-106873. Epub 2020 Jun 22.
• [9] Proteomic investigations of human HERC2 mutants: Insights into the pathobiology of a neurodevelopmental disorder.Biochem Biophys Res Commun. 2019 Apr 30;512(2):421-427. doi: 10.1016/j.bbrc.2019.02.149. Epub 2019 Mar 19.
• [10] Natural and orthogonal model for estimating gene-gene interactions applied to cutaneous melanoma.Hum Genet. 2014 May;133(5):559-74. doi: 10.1007/s00439-013-1392-2. Epub 2013 Nov 17.
• [11] Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.Hum Genet. 2018 Dec;137(11-12):881-896. doi: 10.1007/s00439-018-1942-8. Epub 2018 Oct 10.
• [12] Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer.BMC Cancer. 2016 May 14;16:312. doi: 10.1186/s12885-016-2339-5.
• [13] Genotype-phenotype associations and human eye color.J Hum Genet. 2011 Jan;56(1):5-7. doi: 10.1038/jhg.2010.126. Epub 2010 Oct 14.
• [14] Variants at the OCA2/HERC2 locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs.Br J Dermatol. 2017 Oct;177(4):1066-1073. doi: 10.1111/bjd.15618. Epub 2017 Sep 8.
• [15] Angelman syndrome and severe infections in a patient with de novo 15q11.2-q13.1 deletion and maternally inherited 2q21.3 microdeletion.Gene. 2013 Jan 10;512(2):453-5. doi: 10.1016/j.gene.2012.10.061. Epub 2012 Nov 1.
• [16] Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma.J Invest Dermatol. 2016 May;136(5):930-937. doi: 10.1016/j.jid.2016.01.013. Epub 2016 Jan 29.
• [17] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
• [18] Whole genome sequencing and 6-year follow-up of a mother and daughter with frontometaphyseal dysplasia associated with keratitis, xerosis, poikiloderma, and acro-osteolysis: A case report.Medicine (Baltimore). 2018 Jul;97(28):e11283. doi: 10.1097/MD.0000000000011283.
• [19] The HERC2 ubiquitin ligase is essential for embryonic development and regulates motor coordination.Oncotarget. 2016 Aug 30;7(35):56083-56106. doi: 10.18632/oncotarget.11270.
• [20] Activating HER2 mutations in HER2 gene amplification negative breast cancer.Cancer Discov. 2013 Feb;3(2):224-37. doi: 10.1158/2159-8290.CD-12-0349. Epub 2012 Dec 7.
• [21] Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.Nat Genet. 2018 Sep;50(9):1335-1341. doi: 10.1038/s41588-018-0184-y. Epub 2018 Aug 13.
• [22] Role of p53 in the regulation of irradiation-induced apoptosis in neuroblastoma cells.Mol Genet Metab. 1998 Oct;65(2):155-64. doi: 10.1006/mgme.1998.2747.
• [23] Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.Toxicol Sci. 2015 Jul;146(1):192-201. doi: 10.1093/toxsci/kfv084. Epub 2015 Apr 26.
• [24] Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
• [25] 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.
• [26] 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.
• [27] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [28] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [29] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [30] 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.
• [31] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [32] 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.
• [33] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [34] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [35] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.