Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKJXG52)

DOT Name	Growth arrest-specific protein 1 (GAS1)
Synonyms	GAS-1
Gene Name	GAS1
Related Disease	Nephropathy ( ) Adult glioblastoma ( ) Alobar holoprosencephaly ( ) Bladder cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Clear cell renal carcinoma ( ) Cleft palate ( ) Colorectal carcinoma ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Hereditary sensory and autonomic neuropathy type 1 ( ) Intervertebral disc degeneration ( ) Isolated cleft palate ( ) Lobar holoprosencephaly ( ) Melanoma ( ) Neoplasm ( ) Stomach cancer ( ) Thyroid gland papillary carcinoma ( ) Triple negative breast cancer ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Basal cell nevus syndrome ( ) Bone osteosarcoma ( ) Neuroblastoma ( ) Osteosarcoma ( ) Rabies ( ) Holoprosencephaly ( ) OPTN-related open angle glaucoma ( ) Type-1/2 diabetes ( )
UniProt ID	GAS1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7RHQ
Pfam ID	PF02351
Sequence	MVAALLGGGGEARGGTVPGAWLCLMALLQLLGSAPRGSGLAHGRRLICWQALLQCQGEPE CSYAYNQYAEACAPVLAQHGGGDAPGAAAAAFPASAASFSSRWRCPSHCISALIQLNHTR RGPALEDCDCAQDENCKSTKRAIEPCLPRTSGGGAGGPGAGGVMGCTEARRRCDRDSRCN LALSRYLTYCGKVFNGLRCTDECRTVIEDMLAMPKAALLNDCVCDGLERPICESVKENMA RLCFGAELGNGPGSSGSDGGLDDYYDEDYDDEQRTGGAGGEQPLDDDDGVPHPPRPGSGA AASGGRGDLPYGPGRRSSGGGGRLAPRGAWTPLASILLLLLGPLF
Function	Specific growth arrest protein involved in growth suppression. Blocks entry to S phase. Prevents cycling of normal and transformed cells. Binds 20(S)-hydroxycholesterol (20(S)-OHC).
KEGG Pathway	Hedgehog sig.ling pathway (hsa04340 )
Reactome Pathway	Activation of SMO (R-HSA-5635838 ) Ligand-receptor interactions (R-HSA-5632681 )

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alobar holoprosencephaly	DISON1K9	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Cleft palate	DIS6G5TF	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[9]
Hereditary sensory and autonomic neuropathy type 1	DISLSPO4	Strong	Biomarker	[10]
Intervertebral disc degeneration	DISG3AIM	Strong	Biomarker	[11]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[3]
Lobar holoprosencephaly	DISVK1YW	Strong	Biomarker	[3]
Melanoma	DIS1RRCY	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[8]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[14]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[15]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[4]
Basal cell nevus syndrome	DIST8BC2	moderate	Biomarker	[16]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[17]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[18]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[17]
Rabies	DISSC4V5	Disputed	Biomarker	[19]
Holoprosencephaly	DISR35EC	Limited	Autosomal dominant	[20]
OPTN-related open angle glaucoma	DISDR98A	Limited	Genetic Variation	[21]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[22]
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⏷ Show the Full List of 31 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Growth arrest-specific protein 1 (GAS1) affects the response to substance of Cisplatin.	[44]
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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 Growth arrest-specific protein 1 (GAS1).	[23]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Growth arrest-specific protein 1 (GAS1).	[27]
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19 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 Growth arrest-specific protein 1 (GAS1).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Growth arrest-specific protein 1 (GAS1).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Growth arrest-specific protein 1 (GAS1).	[26]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Growth arrest-specific protein 1 (GAS1).	[28]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Growth arrest-specific protein 1 (GAS1).	[29]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Growth arrest-specific protein 1 (GAS1).	[30]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Growth arrest-specific protein 1 (GAS1).	[31]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Growth arrest-specific protein 1 (GAS1).	[32]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Growth arrest-specific protein 1 (GAS1).	[33]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Growth arrest-specific protein 1 (GAS1).	[34]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Growth arrest-specific protein 1 (GAS1).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Growth arrest-specific protein 1 (GAS1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Growth arrest-specific protein 1 (GAS1).	[37]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Growth arrest-specific protein 1 (GAS1).	[38]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Growth arrest-specific protein 1 (GAS1).	[39]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Growth arrest-specific protein 1 (GAS1).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Growth arrest-specific protein 1 (GAS1).	[41]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Growth arrest-specific protein 1 (GAS1).	[42]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Growth arrest-specific protein 1 (GAS1).	[43]
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⏷ Show the Full List of 19 Drug(s)

References

1	Inhibiting cytosolic translation and autophagy improves health in mitochondrial disease.Hum Mol Genet. 2015 Sep 1;24(17):4829-47. doi: 10.1093/hmg/ddv207. Epub 2015 Jun 3.
2	Microglia induces Gas1 expression in human brain tumor-initiating cells to reduce tumorigenecity.Sci Rep. 2018 Oct 16;8(1):15286. doi: 10.1038/s41598-018-33306-0.
3	Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog.J Clin Invest. 2007 Jun;117(6):1575-84. doi: 10.1172/JCI32032. Epub 2007 May 24.
4	Evidence for two tumor suppressor loci associated with proximal chromosome 9p to q and distal chromosome 9q in bladder cancer and the initial screening for GAS1 and PTC mutations.Cancer Res. 1996 Nov 1;56(21):5039-43.
5	Hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells.Exp Mol Med. 2005 Aug 31;37(4):353-64. doi: 10.1038/emm.2005.45.
6	Downregulation of OCLN and GAS1 in clear cell renal cell carcinoma.Oncol Rep. 2017 Mar;37(3):1487-1496. doi: 10.3892/or.2017.5414. Epub 2017 Jan 31.
7	Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma.Mol Cancer Res. 2016 Sep;14(9):830-40. doi: 10.1158/1541-7786.MCR-16-0032. Epub 2016 Jul 11.
8	Growth arrest-specific gene 1 is downregulated and inhibits tumor growth in gastric cancer.FEBS J. 2012 Oct;279(19):3652-3664. doi: 10.1111/j.1742-4658.2012.08726.x. Epub 2012 Aug 31.
9	Neural stem cells producing an inducible and soluble form of Gas1 target and inhibit intracranial glioma growth.Cytotherapy. 2014 Jul;16(7):1011-23. doi: 10.1016/j.jcyt.2013.12.004. Epub 2014 Feb 12.
10	Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1-->q22.3: exclusion of GAS1 and XPA.Cytogenet Cell Genet. 1997;78(2):140-4. doi: 10.1159/000134649.
11	MiR-184 Regulates Proliferation in Nucleus Pulposus Cells by Targeting GAS1.World Neurosurg. 2017 Jan;97:710-715.e1. doi: 10.1016/j.wneu.2016.01.024. Epub 2016 Jan 22.
12	A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene.Genes Dev. 2008 Nov 1;22(21):2932-40. doi: 10.1101/gad.1714608.
13	Additive effects of the combined expression of soluble forms of GAS1 and PTEN inhibiting glioblastoma growth.Gene Ther. 2018 Sep;25(6):439-449. doi: 10.1038/s41434-018-0020-0. Epub 2018 Jun 25.
14	MiR-34a targets GAS1 to promote cell proliferation and inhibit apoptosis in papillary thyroid carcinoma via PI3K/Akt/Bad pathway.Biochem Biophys Res Commun. 2013 Nov 29;441(4):958-63. doi: 10.1016/j.bbrc.2013.11.010. Epub 2013 Nov 9.
15	A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model.Exp Cell Res. 2014 Oct 1;327(2):307-17. doi: 10.1016/j.yexcr.2014.06.016. Epub 2014 Jun 30.
16	The human growth-arrest-specific gene GAS1 maps outside the candidate region of the gene for nevoid basal cell carcinoma syndrome.Cytogenet Cell Genet. 1995;68(1-2):119-21. doi: 10.1159/000133904.
17	WT1 is involved in the Akt-JNK pathway dependent autophagy through directly regulating Gas1 expression in human osteosarcoma cells.Biochem Biophys Res Commun. 2016 Sep 9;478(1):74-80. doi: 10.1016/j.bbrc.2016.07.090. Epub 2016 Jul 21.
18	Gas1 is induced during and participates in excitotoxic neuronal death.Mol Cell Neurosci. 2002 Mar;19(3):417-29. doi: 10.1006/mcne.2001.1092.
19	Immunogenicity and relative attenuation of different vaccinia-rabies virus recombinants.Arch Virol. 1996;141(6):1055-65. doi: 10.1007/BF01718609.
20	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
21	Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone.Invest Ophthalmol Vis Sci. 2008 May;49(5):1886-97. doi: 10.1167/iovs.07-0414.
22	Gas1 expression in parietal cells of Bowman's capsule in experimental diabetic nephropathy.Histochem Cell Biol. 2017 Jul;148(1):33-47. doi: 10.1007/s00418-017-1550-z. Epub 2017 Mar 18.
23	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
24	Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
25	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
26	Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles. Fertil Steril. 2008 Dec;90(6):2152-64.
27	Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
28	Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
29	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
30	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
31	Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
32	Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
33	Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
34	Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
35	Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
36	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.
37	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
38	The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
39	Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
40	Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
41	Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
42	Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
43	Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.
44	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.