Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXT8A5C)

DOT Name Pituitary-specific positive transcription factor 1 (POU1F1)
Synonyms PIT-1; Growth hormone factor 1; GHF-1
Gene Name POU1F1
Related Disease
Acute myelogenous leukaemia ( )
Chronic kidney disease ( )
Obsessive compulsive disorder ( )
Pituitary hormone deficiency, combined, 1 ( )
Tourette syndrome ( )
Acromegaly ( )
Adenoma ( )
Anemia ( )
Autoimmune disease ( )
Autoimmune polyendocrinopathy ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Colonic neoplasm ( )
Congenital hypothyroidism ( )
Congenital isolated adrenocorticotropic hormone deficiency ( )
Cushing disease ( )
Hyperglycemia ( )
Hypogonadism ( )
Osteoarthritis ( )
Osteosarcoma ( )
Pituitary gland disorder ( )
Pituitary tumor ( )
Precocious puberty ( )
Severe combined immunodeficiency ( )
Adult glioblastoma ( )
Advanced cancer ( )
Anaplastic astrocytoma ( )
Breast adenocarcinoma ( )
Glioblastoma multiforme ( )
Influenza ( )
Panhypopituitarism ( )
Septooptic dysplasia ( )
Werner syndrome ( )
Combined pituitary hormone deficiencies, genetic form ( )
Hypothyroidism due to deficient transcription factors involved in pituitary development or function ( )
Isolated growth hormone deficiency type II ( )
Breast neoplasm ( )
Hypopituitarism ( )
Hypothyroidism ( )
Intellectual disability ( )
Mesothelioma ( )
Pituitary adenoma ( )
Pituitary dwarfism ( )
Type-1/2 diabetes ( )
UniProt ID
PIT1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5WC9
Pfam ID
PF00046 ; PF00157
Sequence
MSCQAFTSADTFIPLNSDASATLPLIMHHSAAECLPVSNHATNVMSTATGLHYSVPSCHY
GNQPSTYGVMAGSLTPCLYKFPDHTLSHGFPPIHQPLLAEDPTAADFKQELRRKSKLVEE
PIDMDSPEIRELEKFANEFKVRRIKLGYTQTNVGEALAAVHGSEFSQTTICRFENLQLSF
KNACKLKAILSKWLEEAEQVGALYNEKVGANERKRKRRTTISIAAKDALERHFGEQNKPS
SQEIMRMAEELNLEKEVVRVWFCNRRQREKRVKTSLNQSLFSISKEHLECR
Function
Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT-3'. Activates growth hormone and prolactin genes.
KEGG Pathway
Growth hormone synthesis, secretion and action (hsa04935 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Definitive Genetic Variation [1]
Chronic kidney disease DISW82R7 Definitive Biomarker [2]
Obsessive compulsive disorder DIS1ZMM2 Definitive Genetic Variation [3]
Pituitary hormone deficiency, combined, 1 DISVFM4T Definitive Semidominant [4]
Tourette syndrome DISX9D54 Definitive Genetic Variation [3]
Acromegaly DISCC73U Strong Biomarker [5]
Adenoma DIS78ZEV Strong Altered Expression [6]
Anemia DISTVL0C Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Biomarker [8]
Autoimmune polyendocrinopathy DISOLDB2 Strong Biomarker [9]
Bone osteosarcoma DIST1004 Strong Altered Expression [10]
Breast cancer DIS7DPX1 Strong Biomarker [11]
Breast carcinoma DIS2UE88 Strong Biomarker [11]
Carcinoma DISH9F1N Strong Altered Expression [12]
Colonic neoplasm DISSZ04P Strong Biomarker [13]
Congenital hypothyroidism DISL5XVU Strong Biomarker [14]
Congenital isolated adrenocorticotropic hormone deficiency DISYMJJV Strong Genetic Variation [15]
Cushing disease DISOG6P2 Strong Biomarker [16]
Hyperglycemia DIS0BZB5 Strong Altered Expression [17]
Hypogonadism DISICMNI Strong Biomarker [18]
Osteoarthritis DIS05URM Strong Altered Expression [19]
Osteosarcoma DISLQ7E2 Strong Altered Expression [10]
Pituitary gland disorder DIS7XB48 Strong Biomarker [20]
Pituitary tumor DISN67JD Strong Altered Expression [21]
Precocious puberty DISYI2XZ Strong Genetic Variation [22]
Severe combined immunodeficiency DIS6MF4Q Strong Altered Expression [23]
Adult glioblastoma DISVP4LU moderate Altered Expression [24]
Advanced cancer DISAT1Z9 moderate Biomarker [24]
Anaplastic astrocytoma DISSBE0K moderate Altered Expression [24]
Breast adenocarcinoma DISMPHJ0 moderate Altered Expression [23]
Glioblastoma multiforme DISK8246 moderate Altered Expression [24]
Influenza DIS3PNU3 moderate Biomarker [25]
Panhypopituitarism DISAKJ4T moderate Genetic Variation [22]
Septooptic dysplasia DISXYR1H moderate Genetic Variation [26]
Werner syndrome DISZY45W moderate Altered Expression [27]
Combined pituitary hormone deficiencies, genetic form DISW6YL6 Supportive Autosomal dominant [26]
Hypothyroidism due to deficient transcription factors involved in pituitary development or function DISCAAEX Supportive Autosomal dominant [28]
Isolated growth hormone deficiency type II DISH3EO5 Supportive Autosomal dominant [29]
Breast neoplasm DISNGJLM Limited Biomarker [30]
Hypopituitarism DIS1QT3G Limited Genetic Variation [31]
Hypothyroidism DISR0H6D Limited Genetic Variation [31]
Intellectual disability DISMBNXP Limited Biomarker [32]
Mesothelioma DISKWK9M Limited Altered Expression [33]
Pituitary adenoma DISJ5R1X Limited Biomarker [34]
Pituitary dwarfism DISI019B Limited Genetic Variation [29]
Type-1/2 diabetes DISIUHAP Limited Altered Expression [35]
------------------------------------------------------------------------------------
⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Manganese DMKT129 Investigative Manganese increases the expression of Pituitary-specific positive transcription factor 1 (POU1F1). [36]
------------------------------------------------------------------------------------

References

1 POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15).Mol Cancer. 2013 Jan 18;12:5. doi: 10.1186/1476-4598-12-5.
2 Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2.Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2625-32. doi: 10.1161/ATVBAHA.113.302249. Epub 2013 Aug 22.
3 Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.Am J Psychiatry. 2015 Jan;172(1):82-93. doi: 10.1176/appi.ajp.2014.13101306. Epub 2014 Oct 31.
4 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
5 Unmasking a new prognostic marker and therapeutic target from the GDNF-RET/PIT1/p14ARF/p53 pathway in acromegaly.EBioMedicine. 2019 May;43:537-552. doi: 10.1016/j.ebiom.2019.04.007. Epub 2019 Apr 8.
6 Confirmation of a new therapeutic option for aggressive or dopamine agonist-resistant prolactin pituitary neuroendocrine tumors.Eur J Endocrinol. 2019 Aug;181(2):C1-C3. doi: 10.1530/EJE-19-0359.
7 Mice lacking the sodium-dependent phosphate import protein, PiT1 (SLC20A1), have a severe defect in terminal erythroid differentiation and early B cell development.Exp Hematol. 2013 May;41(5):432-43.e7. doi: 10.1016/j.exphem.2013.01.004. Epub 2013 Jan 30.
8 Autoimmune Pituitary Disease: New Concepts With Clinical Implications.Endocr Rev. 2020 Apr 1;41(2):bnz003. doi: 10.1210/endrev/bnz003.
9 Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.Pediatr Endocrinol Rev. 2015 Mar;12(3):290-6.
10 Efficient tumor transduction and antitumor efficacy in experimental human osteosarcoma using retroviral replicating vectors.Cancer Gene Ther. 2019 Feb;26(1-2):41-47. doi: 10.1038/s41417-018-0037-y. Epub 2018 Jul 25.
11 POU1F1 transcription factor promotes breast cancer metastasis via recruitment and polarization of macrophages.J Pathol. 2019 Nov;249(3):381-394. doi: 10.1002/path.5324. Epub 2019 Aug 27.
12 Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation.Eur J Endocrinol. 2005 Aug;153(2):335-44. doi: 10.1530/eje.1.01962.
13 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.
14 Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter?.Clin Endocrinol (Oxf). 2005 Aug;63(2):121-30. doi: 10.1111/j.1365-2265.2005.02289.x.
15 Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency.J Clin Endocrinol Metab. 2005 Aug;90(8):4762-70. doi: 10.1210/jc.2005-0570. Epub 2005 May 31.
16 Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing's disease: a case report.BMC Endocr Disord. 2017 Sep 2;17(1):54. doi: 10.1186/s12902-017-0203-5.
17 Combined effects of hyperphosphatemia and hyperglycemia on the calcification of cultured human aortic smooth muscle cells.Exp Ther Med. 2019 Jan;17(1):863-868. doi: 10.3892/etm.2018.7024. Epub 2018 Nov 28.
18 Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.J Clin Endocrinol Metab. 1999 Jan;84(1):50-7. doi: 10.1210/jcem.84.1.5366.
19 1,25-Dihydroxyvitamin D(3) and extracellular inorganic phosphate activate mitogen-activated protein kinase pathway through fibroblast growth factor 23 contributing to hypertrophy and mineralization in osteoarthritic chondrocytes.Exp Biol Med (Maywood). 2012 Mar;237(3):241-53. doi: 10.1258/ebm.2011.011301. Epub 2012 Mar 5.
20 Pituitary Stalk Interruption Syndrome: From Clinical Findings to Pathogenesis.J Neuroendocrinol. 2017 Jan;29(1). doi: 10.1111/jne.12451.
21 Pituitary-specific repression of placental members of the human growth hormone gene family. A possible mechanism for locus regulation.J Biol Chem. 1993 Apr 25;268(12):8473-9.
22 Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: case report and review of possible mechanisms.Hormones (Athens). 2018 Dec;17(4):581-588. doi: 10.1007/s42000-018-0079-4. Epub 2018 Nov 20.
23 Cancer progression by breast tumors with Pit-1-overexpression is blocked by inhibition of metalloproteinase (MMP)-13.Breast Cancer Res. 2014 Dec 20;16(6):505. doi: 10.1186/s13058-014-0505-8.
24 Gefitinib inhibits sodium phosphate co-transporter III isoform 1 in a model of human malignant glioma.Anticancer Res. 2014 Nov;34(11):6527-35.
25 Transgenic mouse model for conditional expression of influenza hemagglutinin-tagged human SLC20A1/PIT1.PLoS One. 2019 Oct 15;14(10):e0223052. doi: 10.1371/journal.pone.0223052. eCollection 2019.
26 Mutation analysis of POUF-1, PROP-1 and HESX-1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo-optic dysplasia. Clin Endocrinol (Oxf). 2005 Feb;62(2):163-8. doi: 10.1111/j.1365-2265.2004.02189.x.
27 Clinical outcome and mechanism of soft tissue calcification in Werner syndrome.Rejuvenation Res. 2008 Aug;11(4):809-19. doi: 10.1089/rej.2007.0649.
28 Congenital hypothyroidism. Orphanet J Rare Dis. 2010 Jun 10;5:17. doi: 10.1186/1750-1172-5-17.
29 Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD. Hum Mol Genet. 2016 Feb 1;25(3):472-83. doi: 10.1093/hmg/ddv486. Epub 2015 Nov 26.
30 Breast cancer metastasis to liver and lung is facilitated by Pit-1-CXCL12-CXCR4 axis.Oncogene. 2018 Mar;37(11):1430-1444. doi: 10.1038/s41388-017-0036-8. Epub 2018 Jan 11.
31 Congenital hypopituitarism due to POU1F1 gene mutation.J Formos Med Assoc. 2011 Jan;110(1):58-61. doi: 10.1016/S0929-6646(11)60009-0.
32 Positive association between POU1F1 and mental retardation in young females in the Chinese Han population.Hum Mol Genet. 2006 Apr 1;15(7):1237-43. doi: 10.1093/hmg/ddl039. Epub 2006 Feb 27.
33 Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus.Cancer Gene Ther. 2013 Dec;20(12):671-7. doi: 10.1038/cgt.2013.67. Epub 2013 Nov 8.
34 Utility of Pit-1 Immunostaining in Distinguishing Pituitary Adenomas of Primitive Differentiation from Null Cell Adenomas.Endocr Pathol. 2017 Dec;28(4):287-292. doi: 10.1007/s12022-017-9503-6.
35 Increased PIT1 and PIT2 Expression in Streptozotocin (STZ)-induced Diabetic Mice Contributes to Uptake of iAs(V).Biomed Environ Sci. 2017 Nov;30(11):792-801. doi: 10.3967/bes2017.107.
36 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.