Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9VFJEL)

• DOT Name: Rab effector Noc2 (RPH3AL)
• Synonyms: No C2 domains protein; Rabphilin-3A-like protein
• Gene Name: RPH3AL
• Related Disease:
  Autism
  Pseudotumor cerebri
  Breast cancer
  Colorectal neoplasm
  Epithelial ovarian cancer
  Medulloblastoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Thyroid gland follicular carcinoma
  Colorectal adenocarcinoma
  Colorectal carcinoma
• UniProt ID: RPH3L_HUMAN
• Pfam ID: PF02318
• Sequence:
  MADTIFGSGNDQWVCPNDRQLALRAKLQTGWSVHTYQTEKQRRKQHLSPAEVEAILQVIQ
  RAERLDVLEQQRIGRLVERLETMRRNVMGNGLSQCLLCGEVLGFLGSSSVFCKDCRKKVC
  TKCGIEASPGQKRPLWLCKICSEQREVWKRSGAWFYKGLPKYILPLKTPGRADDPHFRPL
  PTEPAEREPRSSETSRIYTWARGRVVSSDSDSDSDLSSSSLEDRLPSTGVRDRKGDKPWK
  ESGGSVEAPRMGFTHPPGHLSGCQSSLASGETGTGSADPPGGPRPGLTRRAPVKDTPGRA
  PAADAAPAGPSSCLG
• Function: Rab GTPase effector involved in the late steps of regulated exocytosis, both in endocrine and exocrine cells. Acts as a potential RAB3B effector protein in epithelial cells.
• Tissue Specificity: Moderate to high levels of expression in thyroid, ovary, stomach, heart, pancreas, skeletal muscle, kidney and liver. Also detected in epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Genetic Variation	[1]
Pseudotumor cerebri	DISLLY7S	Definitive	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Thyroid gland follicular carcinoma	DISFK2QT	Strong	Genetic Variation	[5]
Colorectal adenocarcinoma	DISPQOUB	Limited	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Rab effector Noc2 (RPH3AL).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rab effector Noc2 (RPH3AL).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rab effector Noc2 (RPH3AL).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Rab effector Noc2 (RPH3AL).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Rab effector Noc2 (RPH3AL).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Rab effector Noc2 (RPH3AL).	[8]

References

• [1] Individual common variants exert weak effects on the risk for autism spectrum disorders.Hum Mol Genet. 2012 Nov 1;21(21):4781-92. doi: 10.1093/hmg/dds301. Epub 2012 Jul 26.
• [2] Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension.J Neuroophthalmol. 2019 Mar;39(1):50-55. doi: 10.1097/WNO.0000000000000648.
• [3] Clinical Implications of Rabphillin-3A-Like Gene Alterations in Breast Cancer.PLoS One. 2015 Jun 12;10(6):e0129216. doi: 10.1371/journal.pone.0129216. eCollection 2015.
• [4] Mutations of rabphillin-3A-like gene in colorectal cancers.Oncol Rep. 2002 Nov-Dec;9(6):1189-92.
• [5] Cloning of a human ortholog (RPH3AL) of (RNO)Rph3al from a candidate 17p13.3 medulloblastoma tumor suppressor locus.Genomics. 1999 Jul 1;59(1):97-101. doi: 10.1006/geno.1999.5864.
• [6] Clinical significance of a novel single nucleotide polymorphism in the 5' untranslated region of the Rabphillin-3A-Like gene in colorectal adenocarcinoma.Front Biosci. 2008 Jan 1;13:1050-61. doi: 10.2741/2742.
• [7] Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of colorectal cancer.Clin Chim Acta. 2017 Dec;475:157-163. doi: 10.1016/j.cca.2017.10.022. Epub 2017 Oct 23.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.