Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4DQ8F2)

• DOT Name: Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1)
• Synonyms: RAB3 GTPase-activating protein 130 kDa subunit; Rab3-GAP p130; Rab3-GAP
• Gene Name: RAB3GAP1
• Related Disease:
  Advanced cancer
  Retinoblastoma
  Warburg micro syndrome
  Warburg micro syndrome 1
  Alzheimer disease
  Breast carcinoma
  Carcinoma
  Cardiomyopathy
  Colorectal carcinoma
  Hepatocellular carcinoma
  Herpes simplex infection
  Hypogonadism
  Intellectual disability
  Keratoconus
  Lung adenocarcinoma
  Multiple sclerosis
  Neoplasm
  Non-insulin dependent diabetes
  Peripheral neuropathy
  Precancerous condition
  Schizophrenia
  Small-cell lung cancer
  Squamous cell carcinoma
  Acute myelogenous leukaemia
  Cataract
  Martsolf syndrome
  Obsolete cataract-intellectual disability-hypogonadism syndrome
  Prostate cancer
  Prostate carcinoma
  Axonal neuropathy
  Epithelial ovarian cancer
  Melanoma
  Nervous system disease
  Ovarian cancer
• UniProt ID: RB3GP_HUMAN
• Pfam ID: PF19533 ; PF13890
• Sequence:
  MAADSEPESEVFEITDFTTASEWERFISKVEEVLNDWKLIGNSLGKPLEKGIFTSGTWEE
  KSDEISFADFKFSVTHHYLVQESTDKEGKDELLEDVVPQSMQDLLGMNNDFPPRAHCLVR
  WYGLREFVVIAPAAHSDAVLSESKCNLLLSSVSIALGNTGCQVPLFVQIHHKWRRMYVGE
  CQGPGVRTDFEMVHLRKVPNQYTHLSGLLDIFKSKIGCPLTPLPPVSIAIRFTYVLQDWQ
  QYFWPQQPPDIDALVGGEVGGLEFGKLPFGACEDPISELHLATTWPHLTEGIIVDNDVYS
  DLDPIQAPHWSVRVRKAENPQCLLGDFVTEFFKICRRKESTDEILGRSAFEEEGKETADI
  THALSKLTEPASVPIHKLSVSNMVHTAKKKIRKHRGVEESPLNNDVLNTILLFLFPDAVS
  EKPLDGTTSTDNNNPPSESEDYNLYNQFKSAPSDSLTYKLALCLCMINFYHGGLKGVAHL
  WQEFVLEMRFRWENNFLIPGLASGPPDLRCCLLHQKLQMLNCCIERKKARDEGKKTSASD
  VTNIYPGDAGKAGDQLVPDNLKETDKEKGEVGKSWDSWSDSEEEFFECLSDTEELKGNGQ
  ESGKKGGPKEMANLRPEGRLYQHGKLTLLHNGEPLYIPVTQEPAPMTEDLLEEQSEVLAK
  LGTSAEGAHLRARMQSACLLSDMESFKAANPGCSLEDFVRWYSPRDYIEEEVIDEKGNVV
  LKGELSARMKIPSNMWVEAWETAKPIPARRQRRLFDDTREAEKVLHYLAIQKPADLARHL
  LPCVIHAAVLKVKEEESLENISSVKKIIKQIISHSSKVLHFPNPEDKKLEEIIHQITNVE
  ALIARARSLKAKFGTEKCEQEEEKEDLERFVSCLLEQPEVLVTGAGRGHAGRIIHKLFVN
  AQRAAAMTPPEEELKRMGSPEERRQNSVSDFPPPAGREFILRTTVPRPAPYSKALPQRMY
  SVLTKEDFRLAGAFSSDTSFF
• Function: Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and guanine nucleotide exchange factor (GEF) activity towards RAB18. As part of the Rab3GAP complex, acts as a GAP for Rab3 proteins by converting active RAB3-GTP to the inactive form RAB3-GDP. Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones. The Rab3GAP complex, acts as a GEF for RAB18 by promoting the conversion of inactive RAB18-GDP to the active form RAB18-GTP. Required for recruiting and activating RAB18 at the endoplasmic reticulum (ER) membrane where it maintains proper ER structure. Required for normal eye and brain development. May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Retinoblastoma	DISVPNPB	Definitive	Altered Expression	[2]
Warburg micro syndrome	DISSEZ2V	Definitive	Autosomal recessive	[3]
Warburg micro syndrome 1	DIS90EI2	Definitive	Autosomal recessive	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[11]
Hypogonadism	DISICMNI	Strong	Biomarker	[12]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[13]
Keratoconus	DISOONXH	Strong	Genetic Variation	[14]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[15]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[18]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[8]
Precancerous condition	DISV06FL	Strong	Altered Expression	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[7]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[21]
Cataract	DISUD7SL	moderate	Genetic Variation	[22]
Martsolf syndrome	DISF77WN	moderate	GermlineCausalMutation	[23]
Obsolete cataract-intellectual disability-hypogonadism syndrome	DISBWVTW	Supportive	Autosomal recessive	[23]
Prostate cancer	DISF190Y	Disputed	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Disputed	Biomarker	[24]
Axonal neuropathy	DIS5S2BC	Limited	Genetic Variation	[25]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[26]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[27]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[18]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[26]

8 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 Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[31]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[32]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[34]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[35]

1 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 Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1).	[33]

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