Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNWJ7EN)

• DOT Name: Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1)
• Synonyms: Ras-GRF1; Guanine nucleotide-releasing protein; GNRP; Ras-specific nucleotide exchange factor CDC25
• Gene Name: RASGRF1
• Related Disease:
  Acute myelogenous leukaemia
  Glioblastoma multiforme
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Asthma
  Astrocytoma
  Atherosclerosis
  Bipolar disorder
  Cardiovascular disease
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Epilepsy
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Matthew-Wood syndrome
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Osteosarcoma
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Rhabdomyosarcoma
  Schizophrenia
  Stomach cancer
  Systemic lupus erythematosus
  Triple negative breast cancer
  Aarskog-Scott syndrome, X-linked
  Adult lymphoma
  Amyotrophic lateral sclerosis
  Breast cancer
  Breast carcinoma
  Lymphoma
  Neuroblastoma
  Pediatric lymphoma
  Autoimmune disease
  Hermansky-Pudlak syndrome
  Myopia
  Non-small-cell lung cancer
  Refractive error
  Retinitis pigmentosa 3
• UniProt ID: RGRF1_HUMAN
• Pfam ID: PF00169 ; PF00617 ; PF00618 ; PF00621
• Sequence:
  MQKGIRLNDGHVASLGLLARKDGTRKGYLSKRSSDNTKWQTKWFALLQNLLFYFESDSSS
  RPSGLYLLEGCVCDRAPSPKPALSAKEPLEKQHYFTVNFSHENQKALELRTEDAKDCDEW
  VAAIAHASYRTLATEHEALMQKYLHLLQIVETEKTVAKQLRQQIEDGEIEIERLKAEITS
  LLKDNERIQSTQTVAPNDEDSDIKKIKKVQSFLRGWLCRRKWKTIIQDYIRSPHADSMRK
  RNQVVFSMLEAEAEYVQQLHILVNNFLRPLRMAASSKKPPITHDDVSSIFLNSETIMFLH
  QIFYQGLKARISSWPTLVLADLFDILLPMLNIYQEFVRNHQYSLQILAHCKQNRDFDKLL
  KHYEAKPDCEERTLETFLTYPMFQIPRYILTLHELLAHTPHEHVERNSLDYAKSKLEELS
  RIMHDEVSETENIRKNLAIERMIIEGCEILLDTSQTFVRQGSLIQVPMSEKGKITRGRLG
  SLSLKKEGERQCFLFSKHLIICTRGSGGKLHLTKNGVISLIDCTLLEEPESTEEEAKGSG
  QDIDHLDFKIGVEPKDSPPFTVILVASSRQEKAAWTSDISQCVDNIRCNGLMMNAFEENS
  KVTVPQMIKRTREGTREAEMSRSDASLYCDDVDIRFSKTMNSCKVLQIRYASVERLLERL
  TDLRFLSIDFLNTFLHSYRVFTTAIVVLDKLITIYKKPISAIPARWLRSLELLFASGQNN
  KLLYGEPPKSPRATRKFSSPPPLSITKTSSPSRRRKLSLNIPIITGGKALDLAALSCNSN
  GYTSMYSAMSPFSKATLDTSKLYVSSSFTNKIPDEGDTTPEKPEDPSALSKQSSEVSMRE
  ESDIDQNQSDDGDTETSPTKSPTTPKSVKNKNSSEFPLFSYNNGVVMTSCRELDNNRSAL
  SAASAFAIATAGANEGTPNKEKYRRMSLASAGFPPDQRNGDKEFVIRRAATNRVLNVLRH
  WVSKHSQDFETNDELKCKVIGFLEEVMHDPELLTQERKAAANIIRTLTQEDPGDNQITLE
  EITQMAEGVKAEPFENHSALEIAEQLTLLDHLVFKKIPYEEFFGQGWMKLEKNERTPYIM
  KTTKHFNDISNLIASEIIRNEDINARVSAIEKWVAVADICRCLHNYNAVLEITSSMNRSA
  IFRLKKTWLKVSKQTKALIDKLQKLVSSEGRFKNLREALKNCDPPCVPYLGMYLTDLAFI
  EEGTPNYTEDGLVNFSKMRMISHIIREIRQFQQTAYKIEHQAKVTQYLLDQSFVMDEESL
  YESSLRIEPKLPT
• Function: Promotes the exchange of Ras-bound GDP by GTP.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Focal adhesion (hsa04510)
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  Ras activation upon Ca2+ influx through NMDA receptor (R-HSA-442982)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Asthma	DISW9QNS	Strong	Biomarker	[6]
Astrocytoma	DISL3V18	Strong	Altered Expression	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Biomarker	[10]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[12]
Epilepsy	DISBB28L	Strong	Posttranslational Modification	[13]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[14]
Glioma	DIS5RPEH	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
leukaemia	DISS7D1V	Strong	Altered Expression	[17]
Leukemia	DISNAKFL	Strong	Altered Expression	[17]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[18]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[19]
Melanoma	DIS1RRCY	Strong	Biomarker	[20]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[23]
Pancreatic cancer	DISJC981	Strong	Biomarker	[24]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Rhabdomyosarcoma	DISNR7MS	Strong	Genetic Variation	[26]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[27]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[14]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[28]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[29]
Aarskog-Scott syndrome, X-linked	DISNHV62	moderate	Altered Expression	[30]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[31]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[32]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[33]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[33]
Lymphoma	DISN6V4S	moderate	Biomarker	[31]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[34]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[31]
Autoimmune disease	DISORMTM	Limited	Altered Expression	[35]
Hermansky-Pudlak syndrome	DISCY0HQ	Limited	Biomarker	[36]
Myopia	DISK5S60	Limited	Biomarker	[37]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[38]
Refractive error	DISWNEQ1	Limited	Genetic Variation	[39]
Retinitis pigmentosa 3	DIS4VBK1	Limited	Genetic Variation	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1).	[43]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras-specific guanine nucleotide-releasing factor 1 (RASGRF1).	[46]

References

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