Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPOCWR7)

• DOT Name: Retinoic acid-induced protein 3 (GPRC5A)
• Synonyms: G-protein coupled receptor family C group 5 member A; Phorbol ester induced gene 1; PEIG-1; Retinoic acid-induced gene 1 protein; RAIG-1
• Gene Name: GPRC5A
• Related Disease:
  Cutaneous melanoma
  Lung cancer
  Lung neoplasm
  Adenocarcinoma
  Benign prostatic hyperplasia
  Bladder cancer
  Carcinoma of esophagus
  Colitis
  Endometrial carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Matthew-Wood syndrome
  Nasopharyngeal carcinoma
  Neoplasm of esophagus
  Promyelocytic leukaemia
  Psoriasis
  Sarcoma
  Squamous cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Head-neck squamous cell carcinoma
  Prostate cancer
  Rheumatoid arthritis
  Small-cell lung cancer
  Diabetic kidney disease
  Type-1/2 diabetes
  Advanced cancer
  Chronic obstructive pulmonary disease
  Colon cancer
  Colon carcinoma
  Lung carcinoma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Pneumonia
  Pneumonitis
  Prostate carcinoma
• UniProt ID: RAI3_HUMAN
• Pfam ID: PF00003
• Sequence:
  MATTVPDGCRNGLKSKYYRLCDKAEAWGIVLETVATAGVVTSVAFMLTLPILVCKVQDSN
  RRKMLPTQFLFLLGVLGIFGLTFAFIIGLDGSTGPTRFFLFGILFSICFSCLLAHAVSLT
  KLVRGRKPLSLLVILGLAVGFSLVQDVIAIEYIVLTMNRTNVNVFSELSAPRRNEDFVLL
  LTYVLFLMALTFLMSSFTFCGSFTGWKRHGAHIYLTMLLSIAIWVAWITLLMLPDFDRRW
  DDTILSSALAANGWVFLLAYVSPEFWLLTKQRNPMDYPVEDAFCKPQLVKKSYGVENRAY
  SQEEITQGFEETGDTLYAPYSTHFQLQNQPPQKEFSIPRAHAWPSPYKDYEVKKEGS
• Function: Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling. May act as a lung tumor suppressor.
• Tissue Specificity: Expressed at high level in fetal and adult lung tissues but repressed in most human lung cancers . Constitutively expressed in fetal kidney and adult placenta, kidney, prostate, testis, ovary, small intestine, colon, stomach, and spinal cord at low to moderate levels. Not detectable in fetal heart, brain, and liver and adult heart, brain, liver, skeletal muscle, pancreas, spleen, thymus, and peripheral leukocytes. According to PubMed:10783259, expressed at low but detectable level in pancreas and heart.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cutaneous melanoma	DIS3MMH9	Definitive	Genetic Variation	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[2]
Lung neoplasm	DISVARNB	Definitive	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[8]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[6]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[10]
leukaemia	DISS7D1V	Strong	Posttranslational Modification	[11]
Leukemia	DISNAKFL	Strong	Posttranslational Modification	[11]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[12]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[13]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Posttranslational Modification	[14]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[6]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[15]
Psoriasis	DIS59VMN	Strong	Altered Expression	[16]
Sarcoma	DISZDG3U	Strong	Biomarker	[17]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[18]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	moderate	Biomarker	[19]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[19]
Carcinoma	DISH9F1N	moderate	Altered Expression	[20]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[21]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[22]
Prostate cancer	DISF190Y	moderate	Altered Expression	[23]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[24]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[25]
Diabetic kidney disease	DISJMWEY	Disputed	Biomarker	[26]
Type-1/2 diabetes	DISIUHAP	Disputed	Biomarker	[26]
Advanced cancer	DISAT1Z9	Limited	Posttranslational Modification	[6]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Altered Expression	[3]
Colon cancer	DISVC52G	Limited	Biomarker	[7]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[7]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[2]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[27]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[28]
Pancreatic cancer	DISJC981	Limited	Biomarker	[29]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[27]
Pneumonia	DIS8EF3M	Limited	Altered Expression	[3]
Pneumonitis	DIS88E0K	Limited	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Retinoic acid-induced protein 3 (GPRC5A) decreases the response to substance of Arsenic trioxide.	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Retinoic acid-induced protein 3 (GPRC5A).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Retinoic acid-induced protein 3 (GPRC5A).	[50]

25 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 Retinoic acid-induced protein 3 (GPRC5A).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[34]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[36]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[24]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[41]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Retinoic acid-induced protein 3 (GPRC5A).	[42]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[43]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[44]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[45]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[47]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[48]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[49]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[35]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Retinoic acid-induced protein 3 (GPRC5A).	[52]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[53]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Retinoic acid-induced protein 3 (GPRC5A).	[54]

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