Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT53VS75)

• DOT Name: Rap guanine nucleotide exchange factor 5 (RAPGEF5)
• Synonyms: Guanine nucleotide exchange factor for Rap1; M-Ras-regulated Rap GEF; MR-GEF; Related to Epac; Repac
• Gene Name: RAPGEF5
• Related Disease:
  Chronic renal failure
  End-stage renal disease
  Nervous system disease
  Arteriosclerosis
  Atrial fibrillation
  Bipolar disorder
  Breast carcinoma
  Cardiac arrest
  Cardiovascular disease
  Cervical Intraepithelial neoplasia
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Cytomegalovirus infection
  Dementia
  Essential hypertension
  Hepatitis C virus infection
  HIV infectious disease
  Hyperglycemia
  Hyperlipidemia
  IgA nephropathy
  Kidney failure
  Liver cirrhosis
  Major depressive disorder
  Melanoma
  Mental disorder
  Neoplasm
  Nephropathy
  Non-insulin dependent diabetes
  Renal agenesis, unilateral
  Renal cell carcinoma
  Sickle-cell anaemia
  Systemic lupus erythematosus
  Thyroid gland papillary carcinoma
  Type-1 diabetes
  X-linked dominant hypophosphatemic rickets
  Glaucoma/ocular hypertension
  Plasma cell myeloma
  Type-1/2 diabetes
  Dysuria
  Hepatitis B virus infection
  Lupus nephritis
  Myocardial infarction
  Obesity
  Osteoporosis
  Stroke
• UniProt ID: RPGF5_HUMAN
• PDB ID: 1WGY
• Pfam ID: PF00617 ; PF00618
• Sequence:
  MGSSRLRVFDPHLERKDSAAALSDRELPLPTFDVPYFKYIDEEDEDDEWSSRSQSSTEDD
  SVDSLLSDRYVVVSGTPEKILEHLLNDLHLEEVQDKETETLLDDFLLTYTVFMTTDDLCQ
  ALLRHYSAKKYQGKEENSDVPRRKRKVLHLVSQWIALYKDWLPEDEHSKMFLKTIYRNVL
  DDVYEYPILEKELKEFQKILGMHRRHTVDEYSPQKKNKALFHQFSLKENWLQHRGTVTET
  EEIFCHVYITEHSYVSVKAKVSSIAQEILKVVAEKIQYAEEDLALVAITFSGEKHELQPN
  DLVISKSLEASGRIYVYRKDLADTLNPFAENEESQQRSMRILGMNTWDLALELMNFDWSL
  FNSIHEQELIYFTFSRQGSGEHTANLSLLLQRCNEVQLWVATEILLCSQLGKRVQLVKKF
  IKIAAHCKAQRNLNSFFAIVMGLNTASVSRLSQTWEKIPGKFKKLFSELESLTDPSLNHK
  AYRDAFKKMKPPKIPFMPLLLKDVTFIHEGNKTFLDNLVNFEKLHMIADTVRTLRHCRTN
  QFGDLSPKEHQELKSYVNHLYVIDSQQALFELSHRIEPRV
• Function: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation.
• Tissue Specificity: Widely expressed with highest levels in brain.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
End-stage renal disease	DISXA7GG	Definitive	Genetic Variation	[1]
Nervous system disease	DISJ7GGT	Definitive	Genetic Variation	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[7]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[8]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[12]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[13]
Dementia	DISXL1WY	Strong	Biomarker	[14]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[16]
HIV infectious disease	DISO97HC	Strong	Biomarker	[17]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[18]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[19]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[20]
Kidney failure	DISOVQ9P	Strong	Biomarker	[21]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[22]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[23]
Melanoma	DIS1RRCY	Strong	Biomarker	[24]
Mental disorder	DIS3J5R8	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[25]
Nephropathy	DISXWP4P	Strong	Biomarker	[26]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[27]
Renal agenesis, unilateral	DIS53ZJ8	Strong	Biomarker	[28]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[10]
Sickle-cell anaemia	DIS5YNZB	Strong	Biomarker	[29]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[30]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Genetic Variation	[31]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[32]
X-linked dominant hypophosphatemic rickets	DISU3OP6	Strong	Biomarker	[33]
Glaucoma/ocular hypertension	DISLBXBY	moderate	Genetic Variation	[34]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[35]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[36]
Dysuria	DIS7ZXDJ	Limited	Biomarker	[37]
Hepatitis B virus infection	DISLQ2XY	Limited	Biomarker	[38]
Lupus nephritis	DISCVGPZ	Limited	Biomarker	[39]
Myocardial infarction	DIS655KI	Limited	Biomarker	[40]
Obesity	DIS47Y1K	Limited	Biomarker	[27]
Osteoporosis	DISF2JE0	Limited	Biomarker	[41]
Stroke	DISX6UHX	Limited	Genetic Variation	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Rap guanine nucleotide exchange factor 5 (RAPGEF5) affects the response to substance of Methamphetamine.	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[43]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[44]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[45]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[46]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[47]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[49]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[50]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[51]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[52]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[53]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[54]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[54]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[44]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[55]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Rap guanine nucleotide exchange factor 5 (RAPGEF5).	[56]

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