Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDSRUD5)

DOT Name Pterin-4-alpha-carbinolamine dehydratase (PCBD1)
Synonyms
PHS; EC 4.2.1.96; 4-alpha-hydroxy-tetrahydropterin dehydratase; Dimerization cofactor of hepatocyte nuclear factor 1-alpha; DCoH; Dimerization cofactor of HNF1; Phenylalanine hydroxylase-stimulating protein; Pterin carbinolamine dehydratase; PCD
Gene Name PCBD1
Related Disease
Pterin-4 alpha-carbinolamine dehydratase 1 deficiency ( )
Scleroderma ( )
Acute myocardial infarction ( )
Advanced cancer ( )
Cystic fibrosis ( )
Depression ( )
Familial primary hypomagnesemia ( )
Fleck corneal dystrophy ( )
Hydrocephalus ( )
Inflammatory bowel disease ( )
Lung adenocarcinoma ( )
Male infertility ( )
Maturity-onset diabetes of the young ( )
Mental disorder ( )
Non-insulin dependent diabetes ( )
Orofaciodigital syndrome ( )
Orofaciodigital syndrome I ( )
Pancreatic cancer ( )
Polydactyly ( )
Prostate cancer ( )
Prostate carcinoma ( )
Renal hypomagnesemia 2 ( )
Systemic sclerosis ( )
Urinary tract infection ( )
Castration-resistant prostate carcinoma ( )
Neoplasm ( )
Asthma ( )
Bronchiectasis ( )
Colon cancer ( )
Colon carcinoma ( )
Hepatitis C virus infection ( )
Nephropathy ( )
Phenylketonuria ( )
Type-1/2 diabetes ( )
Venous thromboembolism ( )
UniProt ID
PHS_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
4.2.1.96
Pfam ID
PF01329
Sequence
MAGKAHRLSAEERDQLLPNLRAVGWNELEGRDAIFKQFHFKDFNRAFGFMTRVALQAEKL
DHHPEWFNVYNKVHITLSTHECAGLSERDINLASFIEQVAVSMT
Function
Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity. Also acts as a coactivator for HNF1B-dependent transcription.
KEGG Pathway
Folate biosynthesis (hsa00790 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Phenylalanine metabolism (R-HSA-8964208 )
BioCyc Pathway
MetaCyc:HS09360-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Pterin-4 alpha-carbinolamine dehydratase 1 deficiency DISEK2IH Definitive Autosomal recessive [1]
Scleroderma DISVQ342 Definitive Biomarker [2]
Acute myocardial infarction DISE3HTG Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Genetic Variation [4]
Cystic fibrosis DIS2OK1Q Strong Biomarker [5]
Depression DIS3XJ69 Strong Biomarker [3]
Familial primary hypomagnesemia DIS6TTKI Strong Genetic Variation [6]
Fleck corneal dystrophy DISERQJ1 Strong Biomarker [7]
Hydrocephalus DISIZUF7 Strong Biomarker [8]
Inflammatory bowel disease DISGN23E Strong Biomarker [9]
Lung adenocarcinoma DISD51WR Strong Biomarker [10]
Male infertility DISY3YZZ Strong Biomarker [11]
Maturity-onset diabetes of the young DISG75M5 Strong Genetic Variation [6]
Mental disorder DIS3J5R8 Strong Genetic Variation [12]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [13]
Orofaciodigital syndrome DISSB296 Strong Genetic Variation [14]
Orofaciodigital syndrome I DIST27XL Strong Genetic Variation [14]
Pancreatic cancer DISJC981 Strong Biomarker [15]
Polydactyly DIS25BMZ Strong Genetic Variation [14]
Prostate cancer DISF190Y Strong Biomarker [16]
Prostate carcinoma DISMJPLE Strong Biomarker [16]
Renal hypomagnesemia 2 DISAK1QC Strong Genetic Variation [6]
Systemic sclerosis DISF44L6 Strong Biomarker [2]
Urinary tract infection DISMT6UV Strong Biomarker [17]
Castration-resistant prostate carcinoma DISVGAE6 moderate Biomarker [18]
Neoplasm DISZKGEW Disputed Biomarker [19]
Asthma DISW9QNS Limited Biomarker [20]
Bronchiectasis DIS5MYEE Limited Biomarker [21]
Colon cancer DISVC52G Limited Biomarker [22]
Colon carcinoma DISJYKUO Limited Biomarker [22]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [23]
Nephropathy DISXWP4P Limited Genetic Variation [13]
Phenylketonuria DISCU56J Limited Biomarker [24]
Type-1/2 diabetes DISIUHAP Limited Genetic Variation [25]
Venous thromboembolism DISUR7CR Limited Biomarker [26]
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⏷ Show the Full List of 35 Disease(s)
Molecular Interaction Atlas (MIA) 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
Arsenic trioxide DM61TA4 Approved Pterin-4-alpha-carbinolamine dehydratase (PCBD1) decreases the response to substance of Arsenic trioxide. [36]
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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 decreases the methylation of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [27]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [33]
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7 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 Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [28]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [29]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [30]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [31]
DTI-015 DMXZRW0 Approved DTI-015 decreases the expression of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [32]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [34]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Pterin-4-alpha-carbinolamine dehydratase (PCBD1). [35]
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⏷ Show the Full List of 7 Drug(s)

References

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2 Chromosome changes in lymphocytes of patients with scleroderma.Ann Genet. 1995;38(3):145-50.
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4 Predictors of post-cancer diagnosis resignation among Japanese cancer survivors.J Cancer Surviv. 2020 Apr;14(2):106-113. doi: 10.1007/s11764-019-00827-0. Epub 2019 Nov 13.
5 Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia.Respir Res. 2018 Jun 25;19(1):125. doi: 10.1186/s12931-018-0782-3.
6 Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol. 2014 Mar;25(3):574-86.
7 Age-Dependent Subchondral Bone Remodeling and Cartilage Repair in a Minipig Defect Model.Tissue Eng Part C Methods. 2017 Nov;23(11):745-753. doi: 10.1089/ten.TEC.2017.0109. Epub 2017 Oct 27.
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9 Resources used in the treatment of perianal Crohn's disease and the results in a real-life cohort.Gastroenterol Hepatol. 2018 Jun-Jul;41(6):353-361. doi: 10.1016/j.gastrohep.2018.04.006. Epub 2018 May 11.
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11 Sperm defects in primary ciliary dyskinesia and related causes of male infertility.Cell Mol Life Sci. 2020 Jun;77(11):2029-2048. doi: 10.1007/s00018-019-03389-7. Epub 2019 Nov 28.
12 Trajectories of grief: Comparing symptoms from the DSM-5 and ICD-11 diagnoses.Depress Anxiety. 2020 Jan;37(1):17-25. doi: 10.1002/da.22902. Epub 2019 Apr 22.
13 Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function.Hum Mutat. 2001 Oct;18(4):356-7. doi: 10.1002/humu.1201.
14 Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations.Hum Mutat. 2010 Oct;31(10):1142-54. doi: 10.1002/humu.21328.
15 Pancreatic Cancer Database: an integrative resource for pancreatic cancer.Cancer Biol Ther. 2014 Aug;15(8):963-7. doi: 10.4161/cbt.29188. Epub 2014 May 19.
16 High Norwegian prostate cancer mortality: evidence of over-reporting.Scand J Urol. 2018 Apr;52(2):122-128. doi: 10.1080/21681805.2017.1421260. Epub 2018 Jan 11.
17 Is there a conflict between general practitioners applying guidelines for antibiotic prescribing and including their patients' preferences?.Patient Prefer Adherence. 2017 Dec 21;12:9-19. doi: 10.2147/PPA.S147616. eCollection 2018.
18 Rare sugar D-allose induces programmed cell death in hormone refractory prostate cancer cells.Apoptosis. 2008 Sep;13(9):1121-34. doi: 10.1007/s10495-008-0232-7.
19 Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration.Acta Neuropathol. 2018 Apr;135(4):569-579. doi: 10.1007/s00401-017-1802-y. Epub 2018 Jan 3.
20 Ventilation Inhomogeneity and Bronchial Basement Membrane Changes in Chronic Neutrophilic Airway Inflammation.Chest. 2020 Apr;157(4):779-789. doi: 10.1016/j.chest.2019.10.023. Epub 2019 Nov 9.
21 Predicting factors for chronic colonization of Pseudomonas aeruginosa in bronchiectasis.Eur J Clin Microbiol Infect Dis. 2019 Dec;38(12):2299-2304. doi: 10.1007/s10096-019-03675-z. Epub 2019 Aug 31.
22 Expression of prostaglandin H synthase-2 in human brain tumors.Acta Neuropathol. 2001 Aug;102(2):181-7. doi: 10.1007/s004010100373.
23 Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard.Transpl Infect Dis. 2020 Feb;22(1):e13204. doi: 10.1111/tid.13204. Epub 2019 Nov 26.
24 Mutation spectrum of six genes in Chinese phenylketonuria patients obtained through next-generation sequencing.PLoS One. 2014 Apr 4;9(4):e94100. doi: 10.1371/journal.pone.0094100. eCollection 2014.
25 Recessive mutations in PCBD1 cause a new type of early-onset diabetes.Diabetes. 2014 Oct;63(10):3557-64. doi: 10.2337/db13-1784. Epub 2014 May 21.
26 Clinical and laboratory characteristics of children with venous thromboembolism and protein C-deficiency: an observational Israeli-German cohort study.Br J Haematol. 2014 Nov;167(3):385-93. doi: 10.1111/bjh.13039. Epub 2014 Jul 18.
27 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.
28 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
29 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
30 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
31 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
32 Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
33 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.
34 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
35 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
36 The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.