Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXB6LIR)

• DOT Name: Rho family-interacting cell polarization regulator 2 (RIPOR2)
• Gene Name: RIPOR2
• Related Disease:
  Advanced cancer
  Neoplasm
  Pachyonychia congenita 3
  Rheumatoid arthritis
  Autosomal recessive nonsyndromic hearing loss 104
  Cardiovascular disease
  Limb-girdle muscular dystrophy
  Myopathy
  Nonsyndromic genetic hearing loss
  Sensorineural hearing loss disorder
  Hearing loss, autosomal recessive
  Asthma
  Hepatitis
• UniProt ID: RIPR2_HUMAN
• Pfam ID: PF15903
• Sequence:
  MLVGSQSFSPGGPNGIIRSQSFAGFSGLQERRSRCNSFIENSSALKKPQAKLKKMHNLGH
  KNNNPPKEPQPKRVEEVYRALKNGLDEYLEVHQTELDKLTAQLKDMKRNSRLGVLYDLDK
  QIKTIERYMRRLEFHISKVDELYEAYCIQRRLQDGASKMKQAFATSPASKAARESLTEIN
  RSFKEYTENMCTIEVELENLLGEFSIKMKGLAGFARLCPGDQYEIFMKYGRQRWKLKGKI
  EVNGKQSWDGEETVFLPLIVGFISIKVTELKGLATHILVGSVTCETKELFAARPQVVAVD
  INDLGTIKLNLEITWYPFDVEDMTASSGAGNKAAALQRRMSMYSQGTPETPTFKDHSFFR
  WLHPSPDKPRRLSVLSALQDTFFAKLHRSRSFSDLPSLRPSPKAVLELYSNLPDDIFENG
  KAAEEKMPLSLSFSDLPNGDCALTSHSTGSPSNSTNPEITITPAEFNLSSLASQNEGMDD
  TSSASSRNSLGEGQEPKSHLKEEDPEEPRKPASAPSEACRRQSSGAGAEHLFLENDVAEA
  LLQESEEASELKPVELDTSEGNITKQLVKRLTSAEVPMATDRLLSEGSVGGESEGCRSFL
  DGSLEDAFNGLLLALEPHKEQYKEFQDLNQEVMNLDDILKCKPAVSRSRSSSLSLTVESA
  LESFDFLNTSDFDEEEDGDEVCNVGGGADSVFSDTETEKHSYRSVHPEARGHLSEALTED
  TGVGTSVAGSPLPLTTGNESLDITIVRHLQYCTQLVQQIVFSSKTPFVARSLLEKLSRQI
  QVMEKLAAVSDENIGNISSVVEAIPEFHKKLSLLSFWTKCCSPVGVYHSPADRVMKQLEA
  SFARTVNKEYPGLADPVFRTLVSQILDRAEPLLSSSLSSEVVTVFQYYSYFTSHGVSDLE
  SYLSQLARQVSMVQTLQSLRDEKLLQTMSDLAPSNLLAQQEVLRTLALLLTREDNEVSEA
  VTLYLAAASKNQHFREKALLYYCEALTKTNLQLQKAACLALKILEATESIKMLVTLCQSD
  TEEIRNVASETLLSLGEDGRLAYEQLDKFPRDCVKVGGRHGTEVATAF
• Function: Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization. Inhibits chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration. Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion. Required for normal development of inner and outer hair cell stereocilia within the cochlea of the inner ear. Plays a role for maintaining the structural organization of the basal domain of stereocilia. Involved in mechanosensory hair cell function. Required for normal hearing ; [Isoform 2]: Acts as an inhibitor of the small GTPase RHOA. Plays a role in fetal mononuclear myoblast differentiation by promoting filopodia and myotube formation. Maintains naive T lymphocytes in a quiescent state.
• Tissue Specificity: Expressed in primary fetal mononuclear myoblast . Expressed strongly in naive T lymphocytes . Expressed weakly in activated T lymphocytes (at protein level) . Expressed in blood cells and adult tissues of hematopoietic origin, such as the secondary lymphoid organs . Expressed in cytotrophoblast .
• Reactome Pathway:
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Pachyonychia congenita 3	DISZLC6C	Strong	Altered Expression	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Autosomal recessive nonsyndromic hearing loss 104	DISUD6NH	Moderate	Autosomal recessive	[3]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[4]
Limb-girdle muscular dystrophy	DISI9Y1Z	moderate	Biomarker	[5]
Myopathy	DISOWG27	moderate	Altered Expression	[5]
Nonsyndromic genetic hearing loss	DISZX61P	Moderate	Autosomal recessive	[6]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Biomarker	[7]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[3]
Asthma	DISW9QNS	Limited	Genetic Variation	[8]
Hepatitis	DISXXX35	Limited	Biomarker	[9]

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 Rho family-interacting cell polarization regulator 2 (RIPOR2).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[15]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[16]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[19]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[20]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Rho family-interacting cell polarization regulator 2 (RIPOR2).	[25]

References

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• [17] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [18] 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.
• [19] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
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