Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY8CGA3)

• DOT Name: Ral GTPase-activating protein subunit beta (RALGAPB)
• Synonyms: p170
• Gene Name: RALGAPB
• Related Disease:
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chromosomal disorder
  Leukemia
  Metabolic disorder
  Myelodysplastic syndrome
  Neoplasm
  Osteosarcoma
  Plasma cell myeloma
  Renal cell carcinoma
  Retinoblastoma
  Small-cell lung cancer
  Acute myelogenous leukaemia
  Tuberous sclerosis
  Acute leukaemia
  Acute lymphocytic leukaemia
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Childhood acute lymphoblastic leukemia
  Chronic myelogenous leukaemia
  Complex neurodevelopmental disorder
  Cryohydrocytosis
• UniProt ID: RLGPB_HUMAN
• Pfam ID: PF20412
• Sequence:
  MYSEWRSLHLVIQNDQGHTSVLHSYPESVGREVANAVVRPLGQVLGTPSVAGSENLLKTD
  KEVKWTMEVICYGLTLPLDGETVKYCVDVYTDWIMALVLPKDSIPLPVIKEPNQYVQTIL
  KHLQNLFVPRQEQGSSQIRLCLQVLRAIQKLARESSLMARETWEVLLLFLLQINDILLAP
  PTVQGGIAENLAEKLIGVLFEVWLLACTRCFPTPPYWKTAKEMVANWRHHPAVVEQWSKV
  ICALTSRLLRFTYGPSFPAFKVPDEDASLIPPEMDNECVAQTWFRFLHMLSNPVDLSNPA
  IISSTPKFQEQFLNVSGMPQELNQYPCLKHLPQIFFRAMRGISCLVDAFLGISRPRSDSA
  PPTPVNRLSMPQSAAVSTTPPHNRRHRAVTVNKATMKTSTVSTAHASKVQHQTSSTSPLS
  SPNQTSSEPRPLPAPRRPKVNSILNLFGSWLFDAAFVHCKLHNGINRDSSMTAITTQASM
  EFRRKGSQMSTDTMVSNPMFDASEFPDNYEAGRAEACGTLCRIFCSKKTGEEILPAYLSR
  FYMLLIQGLQINDYVCHPVLASVILNSPPLFCCDLKGIDVVVPYFISALETILPDRELSK
  FKSYVNPTELRRSSINILLSLLPLPHHFGTVKSEVVLEGKFSNDDSSSYDKPITFLSLKL
  RLVNILIGALQTETDPNNTQMILGAMLNIVQDSALLEAIGCQMEMGGGENNLKSHSRTNS
  GISSASGGSTEPTTPDSERPAQALLRDYALNTDSAAGLLIRSIHLVTQRLNSQWRQDMSI
  SLAALELLSGLAKVKVMVDSGDRKRAISSVCTYIVYQCSRPAPLHSRDLHSMIVAAFQCL
  CVWLTEHPDMLDEKDCLKEVLEIVELGISGSKSKNNEQEVKYKGDKEPNPASMRVKDAAE
  ATLTCIMQLLGAFPSPSGPASPCSLVNETTLIKYSRLPTINKHSFRYFVLDNSVILAMLE
  QPLGNEQNDFFPSVTVLVRGMSGRLAWAQQLCLLPRGAKANQKLFVPEPRPVPKNDVGFK
  YSVKHRPFPEEVDKIPFVKADLSIPDLHEIVTEELEERHEKLRSGMAQQIAYEIHLEQQS
  EEELQKRSFPDPVTDCKPPPPAQEFQTARLFLSHFGFLSLEALKEPANSRLPPHLIALDS
  TIPGFFDDIGYLDLLPCRPFDTVFIFYMKPGQKTNQEILKNVESSRTVQPHFLEFLLSLG
  WSVDVGRHPGWTGHVSTSWSINCCDDGEGSQQEVISSEDIGASIFNGQKKVLYYADALTE
  IAFVVPSPVESLTDSLESNISDQDSDSNMDLMPGILKQPSLTLELFPNHTDNLNSSQRLS
  PSSRMRKLPQGRPVPPLGPETRVSVVWVERYDDIENFPLSELMTEISTGVETTANSSTSL
  RSTTLEKEVPVIFIHPLNTGLFRIKIQGATGKFNMVIPLVDGMIVSRRALGFLVRQTVIN
  ICRRKRLESDSYSPPHVRRKQKITDIVNKYRNKQLEPEFYTSLFQEVGLKNCSS
• Function: Non-catalytic subunit of the heterodimeric RalGAP1 and RalGAP2 complexes which act as GTPase activators for the Ras-like small GTPases RALA and RALB.
• Tissue Specificity: Highly expressed in brain, mostly in amygdala.
• KEGG Pathway: Ras sig.ling pathway (hsa04014)
• Reactome Pathway: Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[6]
Leukemia	DISNAKFL	Strong	Genetic Variation	[7]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[8]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[12]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[13]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[14]
Acute myelogenous leukaemia	DISCSPTN	moderate	Biomarker	[15]
Tuberous sclerosis	DISEMUGZ	moderate	Biomarker	[16]
Acute leukaemia	DISDQFDI	Limited	Altered Expression	[17]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[18]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Limited	Altered Expression	[19]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Altered Expression	[18]
Chronic myelogenous leukaemia	DIS0301E	Limited	Altered Expression	[19]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[20]
Cryohydrocytosis	DISMQHL3	Limited	Genetic Variation	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[24]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[25]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ral GTPase-activating protein subunit beta (RALGAPB).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ral GTPase-activating protein subunit beta (RALGAPB).	[31]

References

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• [12] Expression of resistance factors (P-glycoprotein, glutathione S-transferase-pi, and topoisomerase II) and their interrelationship to proto-oncogene products in renal cell carcinomas.Cancer. 1993 Jun 15;71(12):3981-7. doi: 10.1002/1097-0142(19930615)71:12<3981::aid-cncr2820711231>3.0.co;2-a.
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• [16] Adipocytes contain a novel complex similar to the tuberous sclerosis complex.Cell Signal. 2006 Oct;18(10):1626-32. doi: 10.1016/j.cellsig.2006.01.002. Epub 2006 Feb 21.
• [17] P-glycoprotein (P-170) expression in acute leukemias.Hematology. 2006 Feb;11(1):35-41. doi: 10.1080/10245330400026204.
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• [19] The role of the MDR-1/P-170 mechanism in the development of multidrug resistance in chronic myeloid leukemia.Leukemia. 1990 Oct;4(10):695-9.
• [20] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
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