Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVEB5LF)

• DOT Name: Fanconi anemia group D2 protein (FANCD2)
• Synonyms: Protein FACD2
• Gene Name: FANCD2
• Related Disease:
  Fanconi anemia complementation group D2
  Non-insulin dependent diabetes
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Ataxia-telangiectasia
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiovascular disease
  Chromosomal disorder
  Colorectal neoplasm
  Endometrial carcinoma
  Familial Alzheimer disease
  Glioma
  Head and neck cancer
  Leukemia
  Multiple sclerosis
  Myelodysplastic syndrome
  Myocardial infarction
  Nervous system disease
  Pancreatic cancer
  Squamous cell carcinoma
  T-cell acute lymphoblastic leukaemia
  Triple negative breast cancer
  Tuberculosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Epithelial ovarian cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  leukaemia
  Lung cancer
  Lung carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Fanconi's anemia
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Hereditary breast carcinoma
  High blood pressure
  Melanoma
• UniProt ID: FACD2_HUMAN
• PDB ID: 6VAA; 6VAD; 6VAE; 6VAF; 7AY1; 7KZQ; 7KZR; 7KZS; 7KZT; 7KZV; 7ZF1; 8A9J; 8A9K
• Pfam ID: PF14631
• Sequence:
  MVSKRRLSKSEDKESLTEDASKTRKQPLSKKTKKSHIANEVEENDSIFVKLLKISGIILK
  TGESQNQLAVDQIAFQKKLFQTLRRHPSYPKIIEEFVSGLESYIEDEDSFRNCLLSCERL
  QDEEASMGASYSKSLIKLLLGIDILQPAIIKTLFEKLPEYFFENKNSDEINIPRLIVSQL
  KWLDRVVDGKDLTTKIMQLISIAPENLQHDIITSLPEILGDSQHADVGKELSDLLIENTS
  LTVPILDVLSSLRLDPNFLLKVRQLVMDKLSSIRLEDLPVIIKFILHSVTAMDTLEVISE
  LREKLDLQHCVLPSRLQASQVKLKSKGRASSSGNQESSGQSCIILLFDVIKSAIRYEKTI
  SEAWIKAIENTASVSEHKVFDLVMLFIIYSTNTQTKKYIDRVLRNKIRSGCIQEQLLQST
  FSVHYLVLKDMCSSILSLAQSLLHSLDQSIISFGSLLYKYAFKFFDTYCQQEVVGALVTH
  ICSGNEAEVDTALDVLLELVVLNPSAMMMNAVFVKGILDYLDNISPQQIRKLFYVLSTLA
  FSKQNEASSHIQDDMHLVIRKQLSSTVFKYKLIGIIGAVTMAGIMAADRSESPSLTQERA
  NLSDEQCTQVTSLLQLVHSCSEQSPQASALYYDEFANLIQHEKLDPKALEWVGHTICNDF
  QDAFVVDSCVVPEGDFPFPVKALYGLEEYDTQDGIAINLLPLLFSQDFAKDGGPVTSQES
  GQKLVSPLCLAPYFRLLRLCVERQHNGNLEEIDGLLDCPIFLTDLEPGEKLESMSAKERS
  FMCSLIFLTLNWFREIVNAFCQETSPEMKGKVLTRLKHIVELQIILEKYLAVTPDYVPPL
  GNFDVETLDITPHTVTAISAKIRKKGKIERKQKTDGSKTSSSDTLSEEKNSECDPTPSHR
  GQLNKEFTGKEEKTSLLLHNSHAFFRELDIEVFSILHCGLVTKFILDTEMHTEATEVVQL
  GPPELLFLLEDLSQKLESMLTPPIARRVPFLKNKGSRNIGFSHLQQRSAQEIVHCVFQLL
  TPMCNHLENIHNYFQCLAAENHGVVDGPGVKVQEYHIMSSCYQRLLQIFHGLFAWSGFSQ
  PENQNLLYSALHVLSSRLKQGEHSQPLEELLSQSVHYLQNFHQSIPSFQCALYLIRLLMV
  ILEKSTASAQNKEKIASLARQFLCRVWPSGDKEKSNISNDQLHALLCIYLEHTESILKAI
  EEIAGVGVPELINSPKDASSSTFPTLTRHTFVVFFRVMMAELEKTVKKIEPGTAADSQQI
  HEEKLLYWNMAVRDFSILINLIKVFDSHPVLHVCLKYGRLFVEAFLKQCMPLLDFSFRKH
  REDVLSLLETFQLDTRLLHHLCGHSKIHQDTRLTQHVPLLKKTLELLVCRVKAMLTLNNC
  REAFWLGNLKNRDLQGEEIKSQNSQESTADESEDDMSSQASKSKATEDGEEDEVSAGEKE
  QDSDESYDDSD
• Function: Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching.
• Tissue Specificity: Highly expressed in germinal center cells of the spleen, tonsil, and reactive lymph nodes, and in the proliferating basal layer of squamous epithelium of tonsil, esophagus, oropharynx, larynx and cervix. Expressed in cytotrophoblastic cells of the placenta and exocrine cells of the pancreas (at protein level). Highly expressed in testis, where expression is restricted to maturing spermatocytes.
• KEGG Pathway: Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  Fanconi Anemia Pathway (R-HSA-6783310)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fanconi anemia complementation group D2	DISC76W3	Definitive	Autosomal recessive	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[7]
Bladder cancer	DISUHNM0	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[10]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[11]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[12]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[13]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[14]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Altered Expression	[16]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[17]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[18]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Biomarker	[19]
Nervous system disease	DISJ7GGT	Strong	Genetic Variation	[18]
Pancreatic cancer	DISJC981	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[21]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Genetic Variation	[22]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[24]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[25]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[17]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[26]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[27]
leukaemia	DISS7D1V	moderate	Biomarker	[17]
Lung cancer	DISCM4YA	moderate	Biomarker	[28]
Lung carcinoma	DISTR26C	moderate	Biomarker	[28]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[25]
Ovarian neoplasm	DISEAFTY	moderate	Biomarker	[25]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[29]
Cervical cancer	DISFSHPF	Limited	Biomarker	[30]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[30]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[31]
Hereditary breast carcinoma	DISAEZT5	Limited	Genetic Variation	[32]
High blood pressure	DISY2OHH	Limited	Biomarker	[33]
Melanoma	DIS1RRCY	Limited	Biomarker	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fanconi anemia group D2 protein (FANCD2).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fanconi anemia group D2 protein (FANCD2).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fanconi anemia group D2 protein (FANCD2).	[45]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[46]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[47]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[48]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[49]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Fanconi anemia group D2 protein (FANCD2).	[50]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[51]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[53]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[54]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[53]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[55]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[56]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[57]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[58]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[59]
SCH 727965	DMCJLD1	Discontinued in Phase 3	SCH 727965 decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[60]
PJ34	DMXO6YH	Preclinical	PJ34 decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[62]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[63]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Fanconi anemia group D2 protein (FANCD2).	[41]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Fanconi anemia group D2 protein (FANCD2).	[50]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Fanconi anemia group D2 protein (FANCD2).	[65]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the ubiquitination of Fanconi anemia group D2 protein (FANCD2).	[43]
DTI-015	DMXZRW0	Approved	DTI-015 increases the ubiquitination of Fanconi anemia group D2 protein (FANCD2).	[43]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the ubiquitination of Fanconi anemia group D2 protein (FANCD2).	[52]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Fanconi anemia group D2 protein (FANCD2).	[64]

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