Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMZTXB5)

• DOT Name: Fanconi anemia group B protein (FANCB)
• Synonyms: Protein FACB; Fanconi anemia-associated polypeptide of 95 kDa; FAAP95
• Gene Name: FANCB
• Related Disease:
  Acute leukaemia
  Acute megakaryoblastic leukemia
  Fanconi anemia complementation group B
  Acute graft versus host disease
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Acute myelomonocytic leukemia M4
  Adult acute monocytic leukemia
  Advanced cancer
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast neoplasm
  Burkitt lymphoma
  Childhood acute lymphoblastic leukemia
  Chronic myelomonocytic leukaemia
  Colon cancer
  Colon carcinoma
  Dementia
  Essential thrombocythemia
  Familial adenomatous polyposis
  Head and neck cancer
  Hereditary breast carcinoma
  Myeloid leukaemia
  Obesity
  Pancytopenia
  Polycythemia vera
  Polyp
  Promyelocytic leukaemia
  Retinoblastoma
  Small lymphocytic lymphoma
  Systemic lupus erythematosus
  T-cell acute lymphoblastic leukaemia
  VACTERL association, X-linked, with or without hydrocephalus
  Wilms tumor
  Bloom syndrome
  Hydrocephalus
  leukaemia
  Fanconi's anemia
  VACTERL with hydrocephalus
  Childhood myelodysplastic syndrome
  Anemia
  Fanconi anemia complementation group A
  Myeloproliferative neoplasm
  Neoplasm
• UniProt ID: FANCB_HUMAN
• PDB ID: 7KZP; 7KZQ; 7KZR; 7KZS; 7KZT; 7KZV
• Sequence:
  MTSKQAMSSNEQERLLCYNGEVLVFQLSKGNFADKEPTKTPILHVRRMVFDRGTKVFVQK
  STGFFTIKEENSHLKIMCCNCVSDFRTGINLPYIVIEKNKKNNVFEYFLLILHSTNKFEM
  RLSFKLGYEMKDGLRVLNGPLILWRHVKAFFFISSQTGKVVSVSGNFSSIQWAGEIENLG
  MVLLGLKECCLSEEECTQEPSKSDYAIWNTKFCVYSLESQEVLSDIYIIPPAYSSVVTYV
  HICATEIIKNQLRISLIALTRKNQLISFQNGTPKNVCQLPFGDPCAVQLMDSGGGNLFFV
  VSFISNNACAVWKESFQVAAKWEKLSLVLIDDFIGSGTEQVLLLFKDSLNSDCLTSFKIT
  DLGKINYSSEPSDCNEDDLFEDKQENRYLVVPPLETGLKVCFSSFRELRQHLLLKEKIIS
  KSYKALINLVQGKDDNTSSAEEKECLVPLCGEEENSVHILDEKLSDNFQDSEQLVEKIWY
  RVIDDSLVVGVKTTSSLKLSLNDVTLSLLMDQAHDSRFRLLKCQNRVIKLSTNPFPAPYL
  MPCEIGLEAKRVTLTPDSKKEESFVCEHPSKKECVQIITAVTSLSPLLTFSKFCCTVLLQ
  IMERESGNCPKDRYVVCGRVFLSLEDLSTGKYLLTFPKKKPIEHMEDLFALLAAFHKSCF
  QITSPGYALNSMKVWLLEHMKCEIIKEFPEVYFCERPGSFYGTLFTWKQRTPFEGILIIY
  SRNQTVMFQCLHNLIRILPINCFLKNLKSGSENFLIDNMAFTLEKELVTLSSLSSAIAKH
  ESNFMQRCEVSKGKSSVVAAALSDRRENIHPYRKELQREKKKMLQTNLKVSGALYREITL
  KVAEVQLKSDFAAQKLSNL
• Function: DNA repair protein required for FANCD2 ubiquitination.
• KEGG Pathway: Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  PKR-mediated signaling (R-HSA-9833482)
  Fanconi Anemia Pathway (R-HSA-6783310)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Definitive	Biomarker	[1]
Acute megakaryoblastic leukemia	DIS0JX3M	Definitive	Genetic Variation	[2]
Fanconi anemia complementation group B	DIS78XCX	Definitive	X-linked	[3]
Acute graft versus host disease	DIS8KLVM	Strong	Biomarker	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[5]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[6]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Altered Expression	[7]
Adult acute monocytic leukemia	DISG6BLX	Strong	Genetic Variation	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Genetic Variation	[10]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[11]
Burkitt lymphoma	DIS9D5XU	Strong	Genetic Variation	[12]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[5]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Biomarker	[13]
Colon cancer	DISVC52G	Strong	Altered Expression	[14]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[14]
Dementia	DISXL1WY	Strong	Biomarker	[15]
Essential thrombocythemia	DISWWK11	Strong	Biomarker	[16]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[17]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[18]
Hereditary breast carcinoma	DISAEZT5	Strong	Biomarker	[11]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Pancytopenia	DISVKEHV	Strong	Biomarker	[6]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[21]
Polyp	DISRSLYF	Strong	Altered Expression	[17]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[22]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[23]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[24]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[25]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Genetic Variation	[26]
VACTERL association, X-linked, with or without hydrocephalus	DISGDBX3	Strong	X-linked	[27]
Wilms tumor	DISB6T16	Strong	Altered Expression	[28]
Bloom syndrome	DISKXQ7J	moderate	Genetic Variation	[29]
Hydrocephalus	DISIZUF7	moderate	Genetic Variation	[18]
leukaemia	DISS7D1V	moderate	Biomarker	[30]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[31]
VACTERL with hydrocephalus	DISB79CB	Supportive	Autosomal recessive	[18]
Childhood myelodysplastic syndrome	DISMN80I	Disputed	Genetic Variation	[32]
Anemia	DISTVL0C	Limited	Biomarker	[33]
Fanconi anemia complementation group A	DIS8PZLI	Limited	Biomarker	[34]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Biomarker	[35]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[36]

3 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 Fanconi anemia group B protein (FANCB).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fanconi anemia group B protein (FANCB).	[49]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Fanconi anemia group B protein (FANCB).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fanconi anemia group B protein (FANCB).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fanconi anemia group B protein (FANCB).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Fanconi anemia group B protein (FANCB).	[40]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fanconi anemia group B protein (FANCB).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fanconi anemia group B protein (FANCB).	[42]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Fanconi anemia group B protein (FANCB).	[43]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fanconi anemia group B protein (FANCB).	[42]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fanconi anemia group B protein (FANCB).	[44]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Fanconi anemia group B protein (FANCB).	[45]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Fanconi anemia group B protein (FANCB).	[46]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Fanconi anemia group B protein (FANCB).	[47]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Fanconi anemia group B protein (FANCB).	[48]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Fanconi anemia group B protein (FANCB).	[44]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Fanconi anemia group B protein (FANCB).	[51]

References

• [1] AML-M0: a review of laboratory features and proposal of new diagnostic criteria.Blood Cells Mol Dis. 1999 Apr;25(2):120-9. doi: 10.1006/bcmd.1999.0236.
• [2] Acute promyelocytic leukemia and constitutional trisomy 21.Cancer Genet Cytogenet. 2006 Mar;165(2):176-9. doi: 10.1016/j.cancergencyto.2005.08.014.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] IPSS poor-risk karyotype as a predictor of outcome for patients with myelodysplastic syndrome following myeloablative stem cell transplantation.Biol Blood Marrow Transplant. 2009 Feb;15(2):205-13. doi: 10.1016/j.bbmt.2008.11.015.
• [5] Current status of diagnosis and prognosis of infant acute leukemia in China.Pediatr Blood Cancer. 2009 Dec;53(6):973-7. doi: 10.1002/pbc.22145.
• [6] Germline Genetic Predisposition to Hematologic Malignancy.J Clin Oncol. 2017 Mar 20;35(9):1018-1028. doi: 10.1200/JCO.2016.70.8644. Epub 2017 Feb 13.
• [7] Prognostic significance of CXCR4 expression in acute myeloid leukemia.Cancer Med. 2019 Nov;8(15):6595-6603. doi: 10.1002/cam4.2535. Epub 2019 Sep 13.
• [8] Involvement of the NUP98 gene in a chromosomal translocation t(11;20)(p15;q11.2) in a patient with acute monocytic leukemia (FAB-M5b).Int J Hematol. 2001 Jul;74(1):53-7. doi: 10.1007/BF02982549.
• [9] Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities. EU Concerted Action 11q23 Workshop.Leukemia. 1998 May;12(5):840-4. doi: 10.1038/sj.leu.2401021.
• [10] Inversion of chromosome 16 in accelerated phase of chronic myeloid leukaemia: report of a case and review of the literature.Med Oncol. 1998 Sep;15(3):199-201. doi: 10.1007/BF02821939.
• [11] Analysis of FANCB and FANCN/PALB2 fanconi anemia genes in BRCA1/2-negative Spanish breast cancer families.Breast Cancer Res Treat. 2009 Feb;113(3):545-51. doi: 10.1007/s10549-008-9945-0. Epub 2008 Feb 27.
• [12] FAB LMB 96 Regimen for Newly Diagnosed Burkitt Lymphoma in Children: Single-center Experience.J Pediatr Hematol Oncol. 2019 Jan;41(1):e7-e11. doi: 10.1097/MPH.0000000000001270.
• [13] Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS).Leukemia. 1999 Mar;13(3):376-85. doi: 10.1038/sj.leu.2401342.
• [14] Molecular Portrait of Metastasis-Competent Circulating Tumor Cells in Colon Cancer Reveals the Crucial Role of Genes Regulating Energy Metabolism and DNA Repair.Clin Chem. 2017 Mar;63(3):700-713. doi: 10.1373/clinchem.2016.263582. Epub 2016 Dec 22.
• [15] Distinguishing neurocognitive deficits in adult patients with NP-C from early onset Alzheimer's dementia.Orphanet J Rare Dis. 2018 Jun 5;13(1):91. doi: 10.1186/s13023-018-0833-3.
• [16] Spontaneous evolution of essential thrombocythaemia into acute megakaryoblastic leukaemia with trisomy 8, trisomy 21 and cutaneous involvement.Eur J Haematol. 2003 Dec;71(6):466-9. doi: 10.1046/j.0902-4441.2003.00139.x.
• [17] Polyposis coli, craniofacial exostosis and astrocytoma: the concomitant occurrence of the Gardner's and Turcot syndromes.Surg Neurol. 1996 Mar;45(3):213-8. doi: 10.1016/0090-3019(95)00380-0.
• [18] X-linked VACTERL with hydrocephalus syndrome: further delineation of the phenotype caused by FANCB mutations. Am J Med Genet A. 2011 Oct;155A(10):2370-80. doi: 10.1002/ajmg.a.33913. Epub 2011 Sep 9.
• [19] Recurrent translocation t(10;17)(p15;q21) in minimally differentiated acute myeloid leukemia results in ZMYND11/MBTD1 fusion.Genes Chromosomes Cancer. 2016 Mar;55(3):237-41. doi: 10.1002/gcc.22326. Epub 2015 Nov 26.
• [20] Targeting Sleep, Food, and Activity in Infants for Obesity Prevention: An RCT.Pediatrics. 2017 Mar;139(3):e20162037. doi: 10.1542/peds.2016-2037.
• [21] Cytogenetic studies on acute nonlymphocytic leukemias following polycythemia vera.Cancer Genet Cytogenet. 1984 Apr;11(4):441-51. doi: 10.1016/0165-4608(84)90025-6.
• [22] A PML/RARA chimeric gene on chromosome 12 in a patient with acute promyelocytic leukemia (M4) associated with a new variant translocation: t(12;15;17)(q24;q24;q11).Med Oncol. 2013 Mar;30(1):409. doi: 10.1007/s12032-012-0409-3. Epub 2013 Jan 6.
• [23] Tumor suppressor gene alteration in adult acute lymphoblastic leukemia (ALL). Analysis of retinoblastoma (Rb) and p53 gene expression in lymphoblasts of patients with de novo, relapsed, or refractory ALL treated in Southwest Oncology Group studies.Leukemia. 1996 Dec;10(12):1901-10.
• [24] Prognostic relevance of the FAB morphological criteria in chronic lymphocytic leukemia: correlations with IgVH gene mutational status and other prognostic markers.Neoplasma. 2006;53(3):219-25.
• [25] Acute megakaryoblastic leukaemia in a patient with systemic lupus erythematosus.Med Oncol. 1997 Mar;14(1):31-4. doi: 10.1007/BF02990942.
• [26] Childhood T-cell acute lymphoblastic leukemia with four distinct immunophenotypes representing different stages of T-cell development.Pediatr Hematol Oncol. 2001 Jun;18(4):267-72. doi: 10.1080/088800101750238577.
• [27] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [28] Prognostic significance of WT1 gene expression in pediatric acute myeloid leukemia.Pediatr Blood Cancer. 2007 Aug;49(2):133-8. doi: 10.1002/pbc.20953.
• [29] Chromosomal aberrations in Bloom syndrome patients with myeloid malignancies.Cancer Genet Cytogenet. 2001 Jul 1;128(1):39-42. doi: 10.1016/s0165-4608(01)00392-2.
• [30] The Role of Regulatory B Cells in Patients with Acute Myeloid Leukemia.Med Sci Monit. 2019 Apr 24;25:3026-3031. doi: 10.12659/MSM.915556.
• [31] Fanconi Anemia. 2002 Feb 14 [updated 2021 Jun 3]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [32] LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia.Leukemia. 2020 Mar;34(3):746-758. doi: 10.1038/s41375-019-0614-6. Epub 2019 Nov 1.
• [33] Fas ligand expression in the bone marrow in myelodysplastic syndromes correlates with FAB subtype and anemia, and predicts survival.Leukemia. 1999 Jan;13(1):44-53. doi: 10.1038/sj.leu.2401233.
• [34] Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype.Mol Genet Genomic Med. 2018 Jan;6(1):77-91. doi: 10.1002/mgg3.350. Epub 2017 Nov 30.
• [35] Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice.Blood. 1999 Mar 15;93(6):2043-56.
• [36] Acute megakaryoblastic leukemia.Leuk Lymphoma. 1995;18 Suppl 1:69-73. doi: 10.3109/10428199509075307.
• [37] 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.
• [38] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [39] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [40] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [41] 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.
• [42] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [43] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [44] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [45] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [46] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [47] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [48] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [49] 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.
• [50] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [51] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.