Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMQXW7S)

• DOT Name: Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1)
• Synonyms: RAPH1; Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 18 protein; Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 9 protein; Lamellipodin; Proline-rich EVH1 ligand 2; PREL-2; Protein RMO1
• Gene Name: RAPH1
• Related Disease:
  Autoimmune disease
  B-cell lymphoma
  Bone osteosarcoma
  Breast adenocarcinoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chronic kidney disease
  Colon carcinoma
  Epstein barr virus infection
  Hepatocellular carcinoma
  Immunodeficiency
  Inflammatory bowel disease
  Intestinal obstruction
  Invasive breast carcinoma
  Late-onset Parkinson disease
  Lymphoma, non-Hodgkin, familial
  Major depressive disorder
  Mycosis fungoides
  Neoplasm
  Non-hodgkin lymphoma
  Osteoarthritis
  Osteosarcoma
  Parkinson disease
  Plasma cell myeloma
  Rheumatoid arthritis
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  T-cell lymphoma
  Advanced cancer
  Hairy cell leukaemia
  Lymphoma
  Mantle cell lymphoma
  Anxiety
  Anxiety disorder
  Classic Hodgkin lymphoma
  Familial adenomatous polyposis
  Idiopathic thrombocytopenic purpura
  Immune system disorder
  Lymphoplasmacytic lymphoma
  Lymphoproliferative syndrome
  Rectal adenocarcinoma
  Rectal carcinoma
  Waldenstrom macroglobulinemia
• UniProt ID: RAPH1_HUMAN
• PDB ID: 4GMV; 4GN1
• Pfam ID: PF00169 ; PF00788
• Sequence:
  MEQLSDEEIDHGAEEDSDKEDQDLDKMFGAWLGELDKLTQSLDSDKPMEPVKRSPLRQET
  NMANFSYRFSIYNLNEALNQGETVDLDALMADLCSIEQELSSIGSGNSKRQITETKATQK
  LPVSRHTLKHGTLKGLSSSSNRIAKPSHASYSLDDVTAQLEQASLSMDEAAQQSVLEDTK
  PLVTNQHRRTASAGTVSDAEVHSISNSSHSSITSAASSMDSLDIDKVTRPQELDLTHQGQ
  PITEEEQAAKLKAEKIRVALEKIKEAQVKKLVIRVHMSDDSSKTMMVDERQTVRQVLDNL
  MDKSHCGYSLDWSLVETVSELQMERIFEDHENLVENLLNWTRDSQNKLIFMERIEKYALF
  KNPQNYLLGKKETAEMADRNKEVLLEECFCGSSVTVPEIEGVLWLKDDGKKSWKKRYFLL
  RASGIYYVPKGKAKVSRDLVCFLQLDHVNVYYGQDYRNKYKAPTDYCLVLKHPQIQKKSQ
  YIKYLCCDDVRTLHQWVNGIRIAKYGKQLYMNYQEALKRTESAYDWTSLSSSSIKSGSSS
  SSIPESQSNHSNQSDSGVSDTQPAGHVRSQSIVSSVFSEAWKRGTQLEESSKARMESMNR
  PYTSLVPPLSPQPKIVTPYTASQPSPPLPPPPPPPPPPPPPPPPPPPPLPSQSAPSAGSA
  APMFVKYSTITRLQNASQHSGALFKPPTPPVMQSQSVKPQILVPPNGVVPPPPPPPPPPT
  PGSAMAQLKPAPCAPSLPQFSAPPPPLKIHQVQHITQVAPPTPPPPPPIPAPLPPQAPPK
  PLVTIPAPTSTKTVAPVVTQAAPPTPTPPVPPAKKQPAFPASYIPPSPPTPPVPVPPPTL
  PKQQSFCAKPPPSPLSPVPSVVKQIASQFPPPPTPPAMESQPLKPVPANVAPQSPPAVKA
  KPKWQPSSIPVPSPDFPPPPPESSLVFPPPPPSPVPAPPPPPPPTASPTPDKSGSPGKKT
  SKTSSPGGKKPPPTPQRNSSIKSSSGAEHPEPKRPSVDSLVSKFTPPAESGSPSKETLPP
  PAAPPKPGKLNLSGVNLPGVLQQGCVSAKAPVLSGRGKDSVVEFPSPPSDSDFPPPPPET
  ELPLPPIEIPAVFSGNTSPKVAVVNPQPQQWSKMSVKKAPPPTRPKRNDSTRLTQAEISE
  QPTMATVVPQVPTSPKSSLSVQPGFLADLNRTLQRKSITRHGSLSSRMSRAEPTATMDDM
  ALPPPPPELLSDQQKAGYGGSHISGYATLRRGPPPAPPKRDQNTKLSRDW
• Function: Mediator of localized membrane signals. Implicated in the regulation of lamellipodial dynamics. Negatively regulates cell adhesion.
• Tissue Specificity: Isoform RMO1-RAPH1 is ubiquitously expressed with highest levels in brain, heart, ovary and developing embryo. Isoform RMO1 is widely expressed with highest levels in liver. Low expression in B-cells.

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[3]
Breast adenocarcinoma	DISMPHJ0	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Chronic kidney disease	DISW82R7	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Epstein barr virus infection	DISOO0WT	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
Immunodeficiency	DIS093I0	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[10]
Intestinal obstruction	DISE52WH	Strong	Biomarker	[2]
Invasive breast carcinoma	DISANYTW	Strong	Altered Expression	[5]
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[11]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[12]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[13]
Mycosis fungoides	DIS62RB8	Strong	Genetic Variation	[14]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[15]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[12]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[16]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[3]
Parkinson disease	DISQVHKL	Strong	Biomarker	[11]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[17]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[18]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[19]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[14]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[20]
Hairy cell leukaemia	DISTD2E5	moderate	Biomarker	[18]
Lymphoma	DISN6V4S	moderate	Altered Expression	[21]
Mantle cell lymphoma	DISFREOV	moderate	Biomarker	[18]
Anxiety	DISIJDBA	Limited	Biomarker	[22]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[22]
Classic Hodgkin lymphoma	DISV1LU6	Limited	Biomarker	[23]
Familial adenomatous polyposis	DISW53RE	Limited	Genetic Variation	[24]
Idiopathic thrombocytopenic purpura	DISFKGJU	Limited	Biomarker	[25]
Immune system disorder	DISAEGPH	Limited	Biomarker	[25]
Lymphoplasmacytic lymphoma	DISMSQ11	Limited	Biomarker	[26]
Lymphoproliferative syndrome	DISMVL8O	Limited	Biomarker	[25]
Rectal adenocarcinoma	DIS8R9VO	Limited	Biomarker	[27]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[27]
Waldenstrom macroglobulinemia	DIS9O23I	Limited	Biomarker	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[32]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[34]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[35]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[35]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[36]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[37]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[38]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[39]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[41]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[42]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[43]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1).	[43]

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