Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTONYC08)

• DOT Name: NUT family member 1 (NUTM1)
• Synonyms: Nuclear protein in testis
• Gene Name: NUTM1
• Related Disease:
  Advanced cancer
  B-cell lymphoma
  Epithelial neoplasm
  Ewing sarcoma/peripheral primitive neuroectodermal tumor
  Germ cell tumor
  Hepatocellular carcinoma
  Laryngeal carcinoma
  Laryngeal disorder
  Lung cancer
  Lung carcinoma
  Malignant thymoma
  Neuroendocrine cancer
  Small-cell lung cancer
  Metastatic sarcoma
  Undifferentiated carcinoma
  Adult lymphoma
  Carcinoid tumor
  leukaemia
  Leukemia
  Lymphoma
  Malignant rhabdoid tumour
  Melanoma
  Pediatric lymphoma
  Rhabdomyosarcoma
  Squamous cell carcinoma
• UniProt ID: NUTM1_HUMAN
• PDB ID: 7XEZ; 7XFG
• Pfam ID: PF12881
• Sequence:
  MASDGASALPGPDMSMKPSAAPSPSPALPFLPPTSDPPDHPPREPPPQPIMPSVFSPDNP
  LMLSAFPSSLLVTGDGGPCLSGAGAGKVIVKVKTEGGSAEPSQTQNFILTQTALNSTAPG
  TPCGGLEGPAPPFVTASNVKTILPSKAVGVSQEGPPGLPPQPPPPVAQLVPIVPLEKAWP
  GPHGTTGEGGPVATLSKPSLGDRSKISKDVYENFRQWQRYKALARRHLSQSPDTEALSCF
  LIPVLRSLARLKPTMTLEEGLPLAVQEWEHTSNFDRMIFYEMAERFMEFEAEEMQIQNTQ
  LMNGSQGLSPATPLKLDPLGPLASEVCQQPVYIPKKAASKTRAPRRRQRKAQRPPAPEAP
  KEIPPEAVKEYVDIMEWLVGTHLATGESDGKQEEEGQQQEEEGMYPDPGLLSYINELCSQ
  KVFVSKVEAVIHPQFLADLLSPEKQRDPLALIEELEQEEGLTLAQLVQKRLMALEEEEDA
  EAPPSFSGAQLDSSPSGSVEDEDGDGRLRPSPGLQGAGGAACLGKVSSSGKRAREVHGGQ
  EQALDSPRGMHRDGNTLPSPSSWDLQPELAAPQGTPGPLGVERRGSGKVINQVSLHQDGH
  LGGAGPPGHCLVADRTSEALPLCWQGGFQPESTPSLDAGLAELAPLQGQGLEKQVLGLQK
  GQQTGGRGVLPQGKEPLAVPWEGSSGAMWGDDRGTPMAQSYDQNPSPRAAGERDDVCLSP
  GVWLSSEMDAVGLELPVQIEEVIESFQVEKCVTEYQEGCQGLGSRGNISLGPGETLVPGD
  TESSVIPCGGTVAAAALEKRNYCSLPGPLRANSPPLRSKENQEQSCETVGHPSDLWAEGC
  FPLLESGDSTLGSSKETLPPTCQGNLLIMGTEDASSLPEASQEAGSRGNSFSPLLETIEP
  VNILDVKDDCGLQLRVSEDTCPLNVHSYDPQGEGRVDPDLSKPKNLAPLQESQESYTTGT
  PKATSSHQGLGSTLPRRGTRNAIVPRETSVSKTHRSADRAKGKEKKKKEAEEEDEELSNF
  AYLLASKLSLSPREHPLSPHHASGGQGSQRASHLLPAGAKGPSKLPYPVAKSGKRALAGG
  PAPTEKTPHSGAQLGVPREKPLALGVVRPSQPRKRRCDSFVTGRRKKRRRSQ
• Function: Plays a role in the regulation of proliferation. Regulates TERT expression by modulating SP1 binding to TERT promoter binding sites.
• Tissue Specificity: Specifically expressed in testis.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[2]
Epithelial neoplasm	DIS0T594	Strong	Genetic Variation	[3]
Ewing sarcoma/peripheral primitive neuroectodermal tumor	DISD4VQC	Strong	Biomarker	[4]
Germ cell tumor	DIS62070	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[6]
Laryngeal disorder	DISDKUQO	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[8]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[9]
Malignant thymoma	DIS59MOU	Strong	Altered Expression	[10]
Neuroendocrine cancer	DISVGJET	Strong	Biomarker	[7]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[11]
Metastatic sarcoma	DISKYC7V	moderate	Biomarker	[12]
Undifferentiated carcinoma	DISIAZST	moderate	Altered Expression	[13]
Adult lymphoma	DISK8IZR	Limited	Genetic Variation	[14]
Carcinoid tumor	DISMNRDC	Limited	Genetic Variation	[14]
leukaemia	DISS7D1V	Limited	Biomarker	[15]
Leukemia	DISNAKFL	Limited	Biomarker	[15]
Lymphoma	DISN6V4S	Limited	Genetic Variation	[14]
Malignant rhabdoid tumour	DIS46HZU	Limited	Altered Expression	[16]
Melanoma	DIS1RRCY	Limited	Biomarker	[14]
Pediatric lymphoma	DIS51BK2	Limited	Genetic Variation	[14]
Rhabdomyosarcoma	DISNR7MS	Limited	Biomarker	[14]
Squamous cell carcinoma	DISQVIFL	Limited	Genetic Variation	[14]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	NUT family member 1 (NUTM1) affects the response to substance of Afimoxifene.	[17]

References

• [1] Identification of genes involved in the regulation of TERT in hepatocellular carcinoma.Cancer Sci. 2019 Feb;110(2):550-560. doi: 10.1111/cas.13884. Epub 2019 Jan 4.
• [2] Dual HDAC and PI3K Inhibitor CUDC-907 Downregulates MYC and Suppresses Growth of MYC-dependent Cancers.Mol Cancer Ther. 2017 Feb;16(2):285-299. doi: 10.1158/1535-7163.MCT-16-0390. Epub 2016 Dec 15.
• [3] NUTM1 Gene Fusions Characterize a Subset of Undifferentiated Soft Tissue and Visceral Tumors.Am J Surg Pathol. 2018 May;42(5):636-645. doi: 10.1097/PAS.0000000000001021.
• [4] NUT carcinoma of the nasal cavity that responded to a chemotherapy regimen for Ewing's sarcoma family of tumors: a case report.BMC Cancer. 2018 Nov 19;18(1):1134. doi: 10.1186/s12885-018-5087-x.
• [5] Nuclear protein in testis midline carcinomas: a lethal and underrecognized entity.Arch Pathol Lab Med. 2011 Nov;135(11):1494-8. doi: 10.5858/arpa.2010-0389-CR.
• [6] Nuclear protein in testis midline carcinoma of larynx: An underdiagnosed entity.Head Neck. 2016 Aug;38(8):E2471-4. doi: 10.1002/hed.24418. Epub 2016 Mar 29.
• [7] Cytologic findings of NUT midline carcinoma in the hilum of the lung.Diagn Cytopathol. 2015 Sep;43(9):739-42. doi: 10.1002/dc.23291. Epub 2015 Jul 3.
• [8] Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro.J Med Genet. 2005 Jul;42(7):558-64. doi: 10.1136/jmg.2004.029686.
• [9] NSD3-NUT-expressing midline carcinoma of the lung: first characterization of primary cancer tissue.Pathol Res Pract. 2015 May;211(5):404-8. doi: 10.1016/j.prp.2014.10.013. Epub 2014 Nov 13.
• [10] NUT rearrangement is uncommon in human thymic epithelial tumors.J Thorac Oncol. 2012 Apr;7(4):744-50. doi: 10.1097/JTO.0b013e3182460f8f.
• [11] SMARCA4-deficient Thoracic Sarcomas: Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses.Am J Surg Pathol. 2019 Apr;43(4):455-465. doi: 10.1097/PAS.0000000000001188.
• [12] First evidence of treatment efficacy in metastatic carcinoma of the parotid gland with BRD4/NUT translocation.J Chemother. 2016 Jun;28(3):242-6. doi: 10.1179/1973947815Y.0000000046.
• [13] NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract.Am J Surg Pathol. 2008 Jun;32(6):828-34. doi: 10.1097/PAS.0b013e31815a3900.
• [14] Systemic therapy in non-conventional cancers of the larynx.Oral Oncol. 2018 Jul;82:61-68. doi: 10.1016/j.oraloncology.2018.05.005. Epub 2018 May 26.
• [15] Cryptic recurrent ACIN1-NUTM1 fusions in non-KMT2A-rearranged infant acute lymphoblastic leukemia.Genes Chromosomes Cancer. 2020 Feb;59(2):125-130. doi: 10.1002/gcc.22808. Epub 2019 Oct 4.
• [16] Targeting chromatin defects in selected solid tumors based on oncogene addiction, synthetic lethality and epigenetic antagonism.Ann Oncol. 2017 Feb 1;28(2):254-269. doi: 10.1093/annonc/mdw552.
• [17] Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2730-5. doi: 10.1073/pnas.1018872108. Epub 2011 Apr 11.