Details of Drug Off-Target (DOT)

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

• DOT Name: GTP-binding protein Rit1 (RIT1)
• Synonyms: EC 3.6.5.2; Ras-like protein expressed in many tissues; Ras-like without CAAX protein 1
• Gene Name: RIT1
• Related Disease:
  Chronic obstructive pulmonary disease
  Noonan syndrome
  Noonan syndrome 8
  Pneumonia
  Aarskog-Scott syndrome, X-linked
  Bladder cancer
  Carcinoma of esophagus
  Cockayne syndrome
  Cornelia de Lange syndrome
  Dubowitz syndrome
  Endometrial cancer
  Endometrial carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Hydrops fetalis
  Hypertrophic cardiomyopathy
  Melanocytic nevus
  Neoplasm
  Neoplasm of esophagus
  Prader-Willi syndrome
  Prostate cancer
  Prostate carcinoma
  Ptosis
  Robinow syndrome
  Seckel syndrome
  Silver-Russell syndrome
  Transitional cell carcinoma
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Crohn disease
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Melanoma
  Carcinoma of liver and intrahepatic biliary tract
  Cardiomyopathy
  Liver cancer
  Adult lymphoma
  Advanced cancer
  Anxiety
  Anxiety disorder
  Clear cell renal carcinoma
  Cutaneous melanoma
  Inflammatory bowel disease
  Lymphoma
  Lymphoma, non-Hodgkin, familial
  Non-hodgkin lymphoma
  Pediatric lymphoma
  Renal cell carcinoma
• UniProt ID: RIT1_HUMAN
• PDB ID: 4KLZ
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MDSGTRPVGSCCSSPAGLSREYKLVMLGAGGVGKSAMTMQFISHRFPEDHDPTIEDAYKI
  RIRIDDEPANLDILDTAGQAEFTAMRDQYMRAGEGFIICYSITDRRSFHEVREFKQLIYR
  VRRTDDTPVVLVGNKSDLKQLRQVTKEEGLALAREFSCPFFETSAAYRYYIDDVFHALVR
  EIRRKEKEAVLAMEKKSKPKNSVWKRLKSPFRKKKDSVT
• Function: Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation.
• Tissue Specificity: Expressed in many tissues.
• Reactome Pathway: Signalling to p38 via RIT and RIN (R-HSA-187706)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Definitive	Genetic Variation	[1]
Noonan syndrome	DIS7Q7DN	Definitive	Autosomal dominant	[2]
Noonan syndrome 8	DISSZJ2I	Definitive	Autosomal dominant	[3]
Pneumonia	DIS8EF3M	Definitive	Genetic Variation	[1]
Aarskog-Scott syndrome, X-linked	DISNHV62	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[6]
Cockayne syndrome	DISW6GL2	Strong	Biomarker	[4]
Cornelia de Lange syndrome	DISEQSXO	Strong	Biomarker	[4]
Dubowitz syndrome	DISRMNLQ	Strong	Biomarker	[4]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[7]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[7]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Hydrops fetalis	DISD9BBF	Strong	Genetic Variation	[9]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[4]
Melanocytic nevus	DISYS32D	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[6]
Prader-Willi syndrome	DISYWMLU	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[12]
Ptosis	DISJZNIY	Strong	Genetic Variation	[13]
Robinow syndrome	DISK1CNU	Strong	Biomarker	[4]
Seckel syndrome	DISEVUBA	Strong	Biomarker	[4]
Silver-Russell syndrome	DISSVJ1D	Strong	Biomarker	[4]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[5]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[11]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[14]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	moderate	Genetic Variation	[16]
Melanoma	DIS1RRCY	moderate	Altered Expression	[17]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Disputed	Biomarker	[15]
Cardiomyopathy	DISUPZRG	Disputed	Genetic Variation	[18]
Liver cancer	DISDE4BI	Disputed	Biomarker	[15]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[19]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[20]
Anxiety	DISIJDBA	Limited	Genetic Variation	[21]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[21]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[22]
Cutaneous melanoma	DIS3MMH9	Limited	Altered Expression	[10]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[23]
Lymphoma	DISN6V4S	Limited	Altered Expression	[19]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Limited	Biomarker	[24]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Biomarker	[24]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[19]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	GTP-binding protein Rit1 (RIT1) affects the response to substance of Fluorouracil.	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of GTP-binding protein Rit1 (RIT1).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of GTP-binding protein Rit1 (RIT1).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of GTP-binding protein Rit1 (RIT1).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GTP-binding protein Rit1 (RIT1).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GTP-binding protein Rit1 (RIT1).	[29]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of GTP-binding protein Rit1 (RIT1).	[30]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of GTP-binding protein Rit1 (RIT1).	[31]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of GTP-binding protein Rit1 (RIT1).	[32]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of GTP-binding protein Rit1 (RIT1).	[29]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of GTP-binding protein Rit1 (RIT1).	[33]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of GTP-binding protein Rit1 (RIT1).	[29]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of GTP-binding protein Rit1 (RIT1).	[29]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of GTP-binding protein Rit1 (RIT1).	[29]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of GTP-binding protein Rit1 (RIT1).	[34]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of GTP-binding protein Rit1 (RIT1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of GTP-binding protein Rit1 (RIT1).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of GTP-binding protein Rit1 (RIT1).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of GTP-binding protein Rit1 (RIT1).	[38]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of GTP-binding protein Rit1 (RIT1).	[39]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of GTP-binding protein Rit1 (RIT1).	[40]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE	DM2D4KY	Investigative	N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of GTP-binding protein Rit1 (RIT1).	[41]

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