Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMUZ0HX)

• DOT Name: RANBP2-like and GRIP domain-containing protein 2 (RGPD2)
• Synonyms: Ran-binding protein 2-like 2; RanBP2-like 2; RanBP2L2
• Gene Name: RGPD2
• Related Disease:
  Female hypogonadism
  Acute leukaemia
  Atrial fibrillation
  Childhood myelodysplastic syndrome
  Chronic myelomonocytic leukemia
  Colorectal carcinoma
  Endometriosis
  Haematological malignancy
  leukaemia
  Melanoma
  Myelodysplastic syndrome
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Triple-A syndrome
  Advanced cancer
  Acute myelogenous leukaemia
  Leukemia
  Nervous system disease
• UniProt ID: RGPD2_HUMAN
• Pfam ID: PF01465 ; PF16704 ; PF00638
• Sequence:
  MRRSKAYGERYLASVQGSAPSPGKKLRGFYFAKLYYEAKEYDLAKKYVCTYLSVQERDPR
  AHRFLGLLYELEENTEKAVECYRRSLELNPPQKDLVLKIAELLCKNDVTDGRAKYWVERA
  AKLFPGSPAIYKLKEHLLDCEGEDGWNKLFDWIQSELYVRPDDVHMNIRLVELYRSNKRL
  KDAVARCHEAERNIALRSSLEWNSCVVQTLKEYLESLQCLESDKSDWRATNTDLLLAYAN
  LMLLTLSTRDVQESRELLESFDSALQSAKSSLGGNDELSATFLEMKGHFYMHAGSLLLKM
  GQHGNNVQWQALSELAALCYVIAFQVPRPKIKLIKGEAGQNLLEMMACDRLSQSGHMLLN
  LSRGKQDFLKEVVETFANKSGQSVLYNALFSSQSSKDTSFLGSDDIGNIDVQEPELEDLA
  RYDVGAIQAHNGSLQHLTWLGLQWNSLPALPGIRKWLKQLFHHLPQETSRLETNAPESIC
  ILDLEVFLLGVVYTSHLQLKEKCNSHHSSYQPLCLPLPVCKRLCTERQKSWWDAVCTLIH
  RKAVPGNSAELRLVVQHEINTLRAQEKHGLQPALLVHWAKCLQKMGRGLNSSYDQQEYIG
  RSVHYWKKVLPLLKIIKKNSIPEPIDPLFKHFHSVDIQASEIVEYEEDAHITFAILDAVH
  GNIEDAVTAFESIKSVVSYWNLALIFHRKAEDIENDAVFPEEQEECKNYLRKTRDYLIKI
  IDDSDSNLSVVKKLPVPLESVKEMLKSVMQELEDYSEGGPLYKNGSLRNADSEIKHSTPS
  PTKYSLSPSKSYKYSPKTPPRWAEDQNSLRKMICQEVKAITKLNSSKSASRHRWPTENYG
  PDSVPDGYQGSQTFHGAPLTVATTGPSVYYSQSPAYNSQYLLRPAANVTPTKGSSNTEFK
  STKEGFSIAVSADGFKFGISEPGNQEKKSEKPLENDTGFQAQDISGQKNGRGVIFGQTSS
  TFTFADVAKSTSGEGFQFGKKDPNFKGFSGAGEKLFSSQCGKMANKANTSGDFEKDDDAC
  KTEDSDDIHFEPVVQMPEKVELVTGEEGEKVLYSQGVKLFRFDAEISQWKERGLGNLKIL
  KNEVNGKPRMLMRRDQVLKVCANHWITTTMNLKPLSGSDRAWMWLASDFSDGDAKLERLA
  AQFKTPELAEEFKQKFEECQRLLLDIPLQTPHKLVDTGRAAKLIQRAEEMKSGLKDFKTF
  LTNDQTKVTEEENKGSGTGAAGASDTTIKPNPENTGPTLEWDNYDLREDALDDNVSSSSV
  HDSPLASSPVRKNIFRFDESTTGFNFSFKSALSLSKSPAKLNQSGTSVGTDEESDVTQEE
  ERDGQYFEPVVPLPDLVEVSSGEENEQVVFSHMAELYRYDKDVGQWKERGIGDIKILQNY
  DNKQVRIVMRRDQVLKLCANHRITPDMSLQNMKGTERVWVWTACDFADGERKVEHLAVRF
  KLQDVADSFKKIFDEAKTAQEKDSLITPHVSRSSTPRESPCGKIAVAVLEETTRERTDVI
  QGDDVADAASEVEVSSTSETTTKAVVSPPKFVFGSESVKRIFSSEKSNPFAFGNSSATGS
  LFGFSFNAPLKSNDSETSSVAQSGSESKVEPKKCELSKNSDIEQSSDSKVKNLSASFPME
  ESSINYTFKTPEKEPPLWHAEFTKEELVQKLSSTTKSADQLNGLLRETEATSAVLMEQIK
  LLKSEIRRLERNQEESAANVEHLKNVLLQFIFLKPGSERESLLPVINTMLQLSPEEKGKL
  AAVAQGLQETSIPKKK

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Female hypogonadism	DISWASB4	Definitive	Biomarker	[1]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[2]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[3]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Genetic Variation	[4]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Endometriosis	DISX1AG8	Strong	Biomarker	[7]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[8]
leukaemia	DISS7D1V	Strong	Genetic Variation	[9]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[10]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[12]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[13]
Triple-A syndrome	DISCOH2J	Strong	Biomarker	[14]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[15]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[16]
Leukemia	DISNAKFL	Limited	Genetic Variation	[17]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[18]

1 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 RANBP2-like and GRIP domain-containing protein 2 (RGPD2).	[19]

References

• [1] A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis. J Clin Invest. 2015 Nov 2;125(11):4295-304. doi: 10.1172/JCI83553. Epub 2015 Oct 20.
• [2] Critical role of retinoid/rexinoid signaling in mediating transformation and therapeutic response of NUP98-RARG leukemia.Leukemia. 2015 May;29(5):1153-62. doi: 10.1038/leu.2014.334. Epub 2014 Dec 16.
• [3] Lamin A mutation impairs interaction with nucleoporin NUP155 and disrupts nucleocytoplasmic transport in atrial fibrillation.Hum Mutat. 2019 Mar;40(3):310-325. doi: 10.1002/humu.23691. Epub 2018 Dec 8.
• [4] Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell proliferation.Cancer Res. 2006 Dec 15;66(24):11781-91. doi: 10.1158/0008-5472.CAN-06-0706.
• [5] NUP98-HBO1-fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis.Blood Adv. 2019 Apr 9;3(7):1047-1060. doi: 10.1182/bloodadvances.2018025007.
• [6] Linking Nucleoporins, Mitosis, and Colon Cancer.Cell Chem Biol. 2016 May 19;23(5):537-539. doi: 10.1016/j.chembiol.2016.05.004.
• [7] Functional polymorphism within NUP210 encoding for nucleoporin GP210 is associated with the risk of endometriosis.Fertil Steril. 2019 Aug;112(2):343-352.e1. doi: 10.1016/j.fertnstert.2019.04.011. Epub 2019 Jun 27.
• [8] NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis.Cancer Cell. 2016 Dec 12;30(6):863-878. doi: 10.1016/j.ccell.2016.10.019. Epub 2016 Nov 23.
• [9] Candidate genes for expansion and transformation of hematopoietic stem cells by NUP98-HOX fusion genes.PLoS One. 2007 Aug 22;2(8):e768. doi: 10.1371/journal.pone.0000768.
• [10] Analysis of Mucosal Melanoma Whole-Genome Landscapes Reveals Clinically Relevant Genomic Aberrations.Clin Cancer Res. 2019 Jun 15;25(12):3548-3560. doi: 10.1158/1078-0432.CCR-18-3442. Epub 2019 Feb 19.
• [11] Loss of p53 accelerates the complications of myelodysplastic syndrome in a NUP98-HOXD13-driven mouse model.Blood. 2012 Oct 11;120(15):3089-97. doi: 10.1182/blood-2012-01-405332. Epub 2012 Aug 27.
• [12] Targeting Nucleoporin POM121-Importin Axis in Prostate Cancer.Cell Chem Biol. 2018 Sep 20;25(9):1056-1058. doi: 10.1016/j.chembiol.2018.09.003.
• [13] Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma.Am J Pathol. 2018 Oct;188(10):2328-2338. doi: 10.1016/j.ajpath.2018.06.013. Epub 2018 Jul 21.
• [14] Loss of the nucleoporin Aladin in central nervous system and fibroblasts of Allgrove Syndrome.Hum Mol Genet. 2019 Dec 1;28(23):3921-3927. doi: 10.1093/hmg/ddz236.
• [15] Importin- and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function.J Cell Sci. 2017 Aug 1;130(15):2564-2578. doi: 10.1242/jcs.197905. Epub 2017 Jun 9.
• [16] Transforming activities of the NUP98-KMT2A fusion gene associated with myelodysplasia and acute myeloid leukemia.Haematologica. 2020 Jul;105(7):1857-1867. doi: 10.3324/haematol.2019.219188. Epub 2019 Sep 26.
• [17] Nuclear pore proteins and cancer.Semin Cell Dev Biol. 2009 Jul;20(5):620-30. doi: 10.1016/j.semcdb.2009.03.003. Epub 2009 Mar 18.
• [18] Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes.Dis Model Mech. 2017 May 1;10(5):559-579. doi: 10.1242/dmm.027730. Epub 2017 Jan 18.
• [19] 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.