Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCTFGW6)

• DOT Name: Regulator of G-protein signaling 22 (RGS22)
• Synonyms: RGS22
• Gene Name: RGS22
• Related Disease:
  Advanced cancer
  Carcinoma of esophagus
  Chromosomal disorder
  Esophageal cancer
  Metastatic malignant neoplasm
  Neoplasm
  Neoplasm of esophagus
  Asthma
  Basal cell carcinoma
  Basal cell neoplasm
  Hepatocellular carcinoma
• UniProt ID: RGS22_HUMAN
• Pfam ID: PF00615
• Sequence:
  MPEKRLTAEPPTITEEEFEDSLATDDFLVDYFNEFLSLPTFSEAIRFNADYGVFEVANDA
  PQFLEKQLKKILQNQQPRNPIYDVVRKGKNEVKPVQMNAPDEDETINVNYNIMCLSREEG
  IKWIKKERLPAFLESDCYFEYRLAKLVSQVRWSKSGMNFTVGSNFSPWIVKKPPSLPPPA
  TEEDNLVIMKKFYVSLGEASYTQTKDWFALAKQSQQTVSTFSLPCCVPYNKLKSPAISSV
  SENFIFDDGVHPRTKKDPSKTNKLISEFEEEEGEEEEVSVSLQDTPSQALLRVYLEKKQD
  VDESLTMHFSTCEEFLSSYIYFILRGAIQQIVGKPVGETPDYINFNNITKVSFDDCFESI
  HGKNFLSELVQTTKERSEEIEQTSLSSKNESAGPESRADWCISHRTYDIGNRKEFERFKK
  FIKGTLGERYWWLWMDIERLKVLKDPGRHQRHLEKMKKCYLVSNGDYYLSAEILSKFKLL
  DGSQWNEEHLRNIQSEVLKPLLLYWAPRFCVTHSASTKYASAELKFWHLRQAKPRKDIDP
  FPQMATLLPLRPKSCIPQIPEIQKEEFSLSQPPKSPNKSPEVKTATQKPWKRELLYPGSS
  KDDVIEKGSKYMSESSKVIHLTSFTDISECLKPQLDRRYAYTEEPRVKTVSDVGALGGSD
  MENLLQSLYVENRAGFFFTKFCEHSGNKLWKNSVYFWFDLQAYHQLFYQETLQPFKVCKQ
  AQYLFATYVAPSATLDIGLQQEKKKEIYMKIQPPFEDLFDTAEEYILLLLLEPWTKMVKS
  DQIAYKKVELVEETRQLDSTYFRKLQALHKETFSKKAEDTTCEIGTGILSLSNVSKRTEY
  WDNVPAEYKHFKFSDLLNNKLEFEHFRQFLETHSSSMDLMCWTDIEQFRRITYRDRNQRK
  AKSIYIKNKYLNKKYFFGPNSPASLYQQNQVMHLSGGWGKILHEQLDAPVLVEIQKHVQN
  RLENVWLPLFLASEQFAARQKIKVQMKDIAEELLLQKAEKKIGVWKPVESKWISSSCKII
  AFRKALLNPVTSRQFQRFVALKGDLLENGLLFWQEVQKYKDLCHSHCDESVIQKKITTII
  NCFINSSIPPALQIDIPVEQAQKIIEHRKELGPYVFREAQMTIFGVLFKFWPQFCEFRKN
  LTDENIMSVLERRQEYNKQKKKLAVLEDEKSGKDGIKQYANTSVPAIKTALLSDSFLGLQ
  PYGRQPTWCYSKYIEALEQERILLKIQEELEKKLFAGLQPLTNFKASSSTMSLKKNMSAH
  SSQK
• Function: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.
• Tissue Specificity: Testis-specific. Expressed in Leydig cells and spermatogenic cells from the spermatogonia to spermatid stages (at protein level).
• Reactome Pathway: G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[1]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[1]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[1]
Asthma	DISW9QNS	moderate	Genetic Variation	[2]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[3]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Regulator of G-protein signaling 22 (RGS22).	[5]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Regulator of G-protein signaling 22 (RGS22).	[6]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Regulator of G-protein signaling 22 (RGS22).	[7]

References

• [1] RGS22, a novel cancer/testis antigen, inhibits epithelial cell invasion and metastasis.Clin Exp Metastasis. 2011 Aug;28(6):541-9. doi: 10.1007/s10585-011-9390-z. Epub 2011 May 1.
• [2] Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.Nat Genet. 2011 Jul 31;43(9):887-92. doi: 10.1038/ng.888.
• [3] Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
• [4] miR-1260b promotes cell migration and invasion of hepatocellular carcinoma by targeting the regulator of G-protein signaling 22.Biotechnol Lett. 2018 Jan;40(1):57-62. doi: 10.1007/s10529-017-2455-6. Epub 2017 Oct 16.
• [5] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [6] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [7] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.