Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8GF6N8)

DOT Name Homeobox protein prophet of Pit-1 (PROP1)
Synonyms PROP-1; Pituitary-specific homeodomain factor
Gene Name PROP1
Related Disease
Pituitary hormone deficiency, combined, 2 ( )
Rheumatoid arthritis ( )
Adenoma ( )
Adrenocortical insufficiency ( )
Adrenogenital syndrome ( )
Alpha-1 antitrypsin deficiency ( )
Brain neoplasm ( )
Colonic neoplasm ( )
Congenital adrenal hyperplasia ( )
Glioblastoma multiforme ( )
Glioma ( )
Growth delay due to insulin-like growth factor type 1 deficiency ( )
Hyperlipidemia ( )
Hypogonadism ( )
Hypothyroidism ( )
Kallmann syndrome ( )
Klinefelter syndrome ( )
Laron syndrome ( )
Meningioma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoporosis ( )
Parkinson disease ( )
Pituitary dwarfism ( )
Pituitary hormone deficiency, combined, 1 ( )
Septooptic dysplasia ( )
Wilson disease ( )
X-linked adrenal hypoplasia congenita ( )
Addison disease ( )
Congenital isolated adrenocorticotropic hormone deficiency ( )
Hypogonadotropic hypogonadism ( )
Hypopituitarism ( )
Combined pituitary hormone deficiencies, genetic form ( )
Hypothyroidism due to deficient transcription factors involved in pituitary development or function ( )
Panhypopituitarism ( )
Endocrine disease ( )
Inflammation ( )
UniProt ID
PROP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00046
Sequence
MEAERRRQAEKPKKGRVGSNLLPERHPATGTPTTTVDSSAPPCRRLPGAGGGRSRFSPQG
GQRGRPHSRRRHRTTFSPVQLEQLESAFGRNQYPDIWARESLARDTGLSEARIQVWFQNR
RAKQRKQERSLLQPLAHLSPAAFSSFLPESTACPYSYAAPPPPVTCFPHPYSHALPSQPS
TGGAFALSHQSEDWYPTLHPAPAGHLPCPPPPPMLPLSLEPSKSWN
Function Possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.
Tissue Specificity Expressed specifically in embryonic pituitary.

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Pituitary hormone deficiency, combined, 2 DISQK4G0 Definitive Autosomal recessive [1]
Rheumatoid arthritis DISTSB4J Definitive Altered Expression [2]
Adenoma DIS78ZEV Strong Altered Expression [3]
Adrenocortical insufficiency DISZ0CPT Strong Genetic Variation [4]
Adrenogenital syndrome DIS2N76U Strong Genetic Variation [5]
Alpha-1 antitrypsin deficiency DISQKEHW Strong Genetic Variation [5]
Brain neoplasm DISY3EKS Strong Biomarker [6]
Colonic neoplasm DISSZ04P Strong Altered Expression [7]
Congenital adrenal hyperplasia DISG873W Strong Genetic Variation [5]
Glioblastoma multiforme DISK8246 Strong Altered Expression [6]
Glioma DIS5RPEH Strong Genetic Variation [8]
Growth delay due to insulin-like growth factor type 1 deficiency DISHA2HH Strong Genetic Variation [9]
Hyperlipidemia DIS61J3S Strong Genetic Variation [10]
Hypogonadism DISICMNI Strong Genetic Variation [11]
Hypothyroidism DISR0H6D Strong Genetic Variation [12]
Kallmann syndrome DISO3HDG Strong Genetic Variation [13]
Klinefelter syndrome DISOUI7W Strong Genetic Variation [14]
Laron syndrome DISW9H7W Strong Genetic Variation [9]
Meningioma DISPT4TG Strong Altered Expression [6]
Neoplasm DISZKGEW Strong Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [16]
Obesity DIS47Y1K Strong Biomarker [17]
Osteoporosis DISF2JE0 Strong Genetic Variation [10]
Parkinson disease DISQVHKL Strong Altered Expression [18]
Pituitary dwarfism DISI019B Strong Biomarker [19]
Pituitary hormone deficiency, combined, 1 DISVFM4T Strong GermlineCausalMutation [20]
Septooptic dysplasia DISXYR1H Strong Genetic Variation [21]
Wilson disease DISVS9H7 Strong Genetic Variation [5]
X-linked adrenal hypoplasia congenita DISNMXY8 Strong Biomarker [17]
Addison disease DIS7HNOH moderate Genetic Variation [22]
Congenital isolated adrenocorticotropic hormone deficiency DISYMJJV moderate Genetic Variation [23]
Hypogonadotropic hypogonadism DIS8JSKR moderate Genetic Variation [14]
Hypopituitarism DIS1QT3G moderate Biomarker [24]
Combined pituitary hormone deficiencies, genetic form DISW6YL6 Supportive Autosomal dominant [20]
Hypothyroidism due to deficient transcription factors involved in pituitary development or function DISCAAEX Supportive Autosomal dominant [25]
Panhypopituitarism DISAKJ4T Supportive Autosomal recessive [26]
Endocrine disease DISRGY2N Limited Genetic Variation [27]
Inflammation DISJUQ5T Limited Biomarker [28]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Homeobox protein prophet of Pit-1 (PROP1). [29]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Homeobox protein prophet of Pit-1 (PROP1). [30]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Homeobox protein prophet of Pit-1 (PROP1). [31]
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References

1 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.
2 Retinoic acid signalling is a candidate regulator of the expression of pituitary-specific transcription factor Prop1 in the developing rodent pituitary.J Neuroendocrinol. 2018 Mar;30(3):e12570. doi: 10.1111/jne.12570.
3 PROP1 overexpression in corticotrophinomas: evidence for the role of PROP1 in the maintenance of cells committed to corticotrophic differentiation.Clinics (Sao Paulo). 2013 Jun;68(6):887-91. doi: 10.6061/clinics/2013(06)26.
4 PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis. J Clin Endocrinol Metab. 2004 Oct;89(10):5256-65. doi: 10.1210/jc.2004-0661.
5 Exome-based search for recurrent disease-causing alleles in Russian population.Eur J Med Genet. 2019 Jul;62(7):103656. doi: 10.1016/j.ejmg.2019.04.013. Epub 2019 Apr 24.
6 Prop-1 gene expression in human pituitary tumors.J Clin Endocrinol Metab. 1999 Jul;84(7):2581-4. doi: 10.1210/jcem.84.7.5974.
7 Growth hormone is permissive for neoplastic colon growth.Proc Natl Acad Sci U S A. 2016 Jun 7;113(23):E3250-9. doi: 10.1073/pnas.1600561113. Epub 2016 May 25.
8 Suprasellar mass mimicking a hypothalamic glioma in a patient with a complete PROP1 deletion.Eur J Med Genet. 2013 Aug;56(8):445-51. doi: 10.1016/j.ejmg.2013.06.006. Epub 2013 Jul 3.
9 Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?.Mech Ageing Dev. 2005 Feb;126(2):305-7. doi: 10.1016/j.mad.2004.08.022.
10 PROP-1 gene mutations in a 63-year-old woman presenting with osteoporosis and hyperlipidaemia.Hormones (Athens). 2013 Jan-Mar;12(1):128-34. doi: 10.1007/BF03401294.
11 An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain.J Clin Endocrinol Metab. 2005 Aug;90(8):4880-7. doi: 10.1210/jc.2005-0119. Epub 2005 Jun 7.
12 Hypopituitarism oddities: congenital causes.Horm Res. 2007;68 Suppl 5:138-44. doi: 10.1159/000110610. Epub 2007 Dec 10.
13 Mutations of the GnRH receptor gene: a new cause of autosomal-recessive hypogonadotropic hypogonadism.Arch Med Res. 1999 Nov-Dec;30(6):481-5. doi: 10.1016/s0188-4409(99)00072-7.
14 The genetic basis of female reproductive disorders: etiology and clinical testing.Mol Cell Endocrinol. 2013 May 6;370(1-2):138-48. doi: 10.1016/j.mce.2013.02.016. Epub 2013 Mar 14.
15 A small molecule, (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol suppresses tumor growth via inhibition of IkappaB kinase in colorectal cancer in vivo and in vitro.Oncotarget. 2017 Aug 24;8(53):91258-91269. doi: 10.18632/oncotarget.20440. eCollection 2017 Oct 31.
16 MMPP Attenuates Non-Small Cell Lung Cancer Growth by Inhibiting the STAT3 DNA-Binding Activity via Direct Binding to the STAT3 DNA-Binding Domain.Theranostics. 2017 Oct 16;7(18):4632-4642. doi: 10.7150/thno.18630. eCollection 2017.
17 Hypogonadotropic hypogonadism.Semin Reprod Med. 2002 Nov;20(4):327-38. doi: 10.1055/s-2002-36707.
18 A Novel Small Molecule Supports the Survival of Cultured Dopamine Neurons and May Restore the Dopaminergic Innervation of the Brain in the MPTP Mouse Model of Parkinson's Disease.ACS Chem Neurosci. 2019 Oct 16;10(10):4337-4349. doi: 10.1021/acschemneuro.9b00396. Epub 2019 Sep 11.
19 Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism.Clin Endocrinol (Oxf). 2015 Jun;82(6):876-84. doi: 10.1111/cen.12706. Epub 2015 Feb 6.
20 Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet. 1998 Feb;18(2):147-9. doi: 10.1038/ng0298-147.
21 Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency.Horm Res Paediatr. 2015;84(3):153-8. doi: 10.1159/000433468. Epub 2015 Jun 24.
22 Central hypocortisolism as part of combined pituitary hormone deficiency due to mutations of PROP-1 gene.Eur J Endocrinol. 2000 Sep;143(3):347-52. doi: 10.1530/eje.0.1430347.
23 Long-term follow-up of combined pituitary hormone deficiency in two siblings with a Prophet of Pit-1 gene mutation.Gynecol Endocrinol. 2006 Dec;22(12):704-9. doi: 10.1080/09513590601030290.
24 Therapy-Induced Growth and Sexual Maturation in a Developmentally Infantile Adult Patient with a PROP1 Mutation.Front Endocrinol (Lausanne). 2017 Nov 13;8:309. doi: 10.3389/fendo.2017.00309. eCollection 2017.
25 Congenital hypothyroidism. Orphanet J Rare Dis. 2010 Jun 10;5:17. doi: 10.1186/1750-1172-5-17.
26 Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
27 Persistent Prop1 expression delays gonadotrope differentiation and enhances pituitary tumor susceptibility.Hum Mol Genet. 2001 May 15;10(11):1141-53. doi: 10.1093/hmg/10.11.1141.
28 (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) Phenol Ameliorates MPTP-Induced Dopaminergic Neurodegeneration by Inhibiting the STAT3 Pathway.Int J Mol Sci. 2019 May 29;20(11):2632. doi: 10.3390/ijms20112632.
29 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
30 Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells. Br J Pharmacol. 2013 May;169(1):167-78.
31 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.