Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6C00Z1)

DOT Name Four and a half LIM domains protein 5 (FHL5)
Synonyms FHL-5; Activator of cAMP-responsive element modulator in testis; Activator of CREM in testis
Gene Name FHL5
Related Disease
Adult glioblastoma ( )
Prostate carcinoma ( )
Tuberculosis ( )
Adenocarcinoma ( )
Adenoma ( )
Alzheimer disease ( )
Atrial fibrillation ( )
Breast cancer ( )
Breast carcinoma ( )
Cerebrovascular disease ( )
Clear cell renal carcinoma ( )
Dementia ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Glioblastoma multiforme ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Hereditary hemophagocytic lymphohistiocytosis ( )
Insomnia ( )
Malaria ( )
Multiple sclerosis ( )
Myocardial infarction ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Pertussis ( )
Prostate cancer ( )
Psychotic disorder ( )
Renal cell carcinoma ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
Systemic sclerosis ( )
Type-1/2 diabetes ( )
Coronary heart disease ( )
Hepatocellular carcinoma ( )
Intestinal disorder ( )
Type-1 diabetes ( )
Advanced cancer ( )
Aplasia cutis congenita ( )
Asthma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Chronic obstructive pulmonary disease ( )
Corpus callosum, agenesis of ( )
Liver cancer ( )
Mental disorder ( )
Non-insulin dependent diabetes ( )
UniProt ID
FHL5_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1X68
Pfam ID
PF00412
Sequence
MTTAHFYCQYCTASLLGKKYVLKDDSPYCVTCYDRVFSNYCEECKKPIESDSKDLCYKDR
HWHEGCFKCTKCNHSLVEKPFAAKDERLLCTECYSNECSSKCFHCKRTIMPGSRKMEFKG
NYWHETCFVCENCRQPIGTKPLISKESGNYCVPCFEKEFAHYCNFCKKVITSGGITFCDQ
LWHKECFLCSGCRKDLCEEQFMSRDDYPFCVDCYNHLYANKCVACSKPISGLTGAKFICF
QDSQWHSECFNCGKCSVSLVGKGFLTQNKEIFCQKCGSGMDTDI
Function May be involved in the regulation of spermatogenesis. Stimulates CREM transcriptional activity in a phosphorylation-independent manner.
Tissue Specificity Testis-specific (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Definitive Biomarker [1]
Prostate carcinoma DISMJPLE Definitive Biomarker [2]
Tuberculosis DIS2YIMD Definitive Genetic Variation [3]
Adenocarcinoma DIS3IHTY Strong Biomarker [2]
Adenoma DIS78ZEV Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Atrial fibrillation DIS15W6U Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Genetic Variation [7]
Breast carcinoma DIS2UE88 Strong Genetic Variation [7]
Cerebrovascular disease DISAB237 Strong Genetic Variation [8]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [9]
Dementia DISXL1WY Strong Altered Expression [10]
Epithelial ovarian cancer DIS56MH2 Strong Genetic Variation [11]
Esophageal squamous cell carcinoma DIS5N2GV Strong Genetic Variation [12]
Glioblastoma multiforme DISK8246 Strong Biomarker [1]
Glioma DIS5RPEH Strong Genetic Variation [13]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [14]
Hereditary hemophagocytic lymphohistiocytosis DISQP21Z Strong Genetic Variation [15]
Insomnia DIS0AFR7 Strong Biomarker [16]
Malaria DISQ9Y50 Strong Biomarker [17]
Multiple sclerosis DISB2WZI Strong Biomarker [18]
Myocardial infarction DIS655KI Strong Genetic Variation [19]
Neoplasm DISZKGEW Strong Altered Expression [20]
Ovarian cancer DISZJHAP Strong Genetic Variation [11]
Ovarian neoplasm DISEAFTY Strong Genetic Variation [11]
Parkinson disease DISQVHKL Strong Biomarker [21]
Pertussis DISQZUE7 Strong Biomarker [22]
Prostate cancer DISF190Y Strong Biomarker [2]
Psychotic disorder DIS4UQOT Strong Biomarker [23]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [9]
Rheumatoid arthritis DISTSB4J Strong Biomarker [24]
Schizophrenia DISSRV2N Strong Genetic Variation [25]
Systemic sclerosis DISF44L6 Strong Altered Expression [26]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [27]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [28]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [29]
Intestinal disorder DISGPMUQ moderate Biomarker [30]
Type-1 diabetes DIS7HLUB moderate Genetic Variation [31]
Advanced cancer DISAT1Z9 Limited Biomarker [9]
Aplasia cutis congenita DISMDAYM Limited Biomarker [32]
Asthma DISW9QNS Limited Biomarker [33]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Biomarker [29]
Chronic obstructive pulmonary disease DISQCIRF Limited Genetic Variation [34]
Corpus callosum, agenesis of DISO9P40 Limited Biomarker [32]
Liver cancer DISDE4BI Limited Biomarker [29]
Mental disorder DIS3J5R8 Limited Biomarker [23]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [35]
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⏷ Show the Full List of 47 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
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Four and a half LIM domains protein 5 (FHL5). [36]
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2 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 decreases the methylation of Four and a half LIM domains protein 5 (FHL5). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Four and a half LIM domains protein 5 (FHL5). [38]
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References

1 Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial.Lancet Oncol. 2017 Oct;18(10):1373-1385. doi: 10.1016/S1470-2045(17)30517-X. Epub 2017 Aug 23.
2 Early Response Monitoring Following Radiation Therapy by Using [(18)F]FDG and [(11)C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration.Molecules. 2017 Nov 10;22(11):1946. doi: 10.3390/molecules22111946.
3 Mutations in lysX as the new and reliable markers for tuberculosis Beijing and modern Beijing strains.Tuberculosis (Edinb). 2016 Mar;97:33-7. doi: 10.1016/j.tube.2015.12.006. Epub 2015 Dec 29.
4 Expression of cAMP-responsive element binding protein and inducible cAMP early repressor in hyperfunctioning thyroid adenomas.Eur J Endocrinol. 2002 Jun;146(6):759-66. doi: 10.1530/eje.0.1460759.
5 Inflammatory markers in Alzheimer's disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies.J Neurol Neurosurg Psychiatry. 2019 May;90(5):590-598. doi: 10.1136/jnnp-2018-319148. Epub 2019 Jan 10.
6 Paroxysmal Atrial Fibrillation in the Course of Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis.Biomed Res Int. 2017;2017:5049802. doi: 10.1155/2017/5049802. Epub 2017 Feb 9.
7 Association of vitamin D receptor gene polymorphisms with breast cancer risk in an Egyptian population.Tumour Biol. 2017 Oct;39(10):1010428317727738. doi: 10.1177/1010428317727738.
8 alpha-1-Antichymotrypsin gene A1252G variant (ACT Isehara-1) is associated with a lacunar type of ischemic cerebrovascular disease.J Hum Genet. 2001;46(1):45-7. doi: 10.1007/s100380170125.
9 Dual-Tracer PET/CT Differentiates 2 Types of Primary Cancers and Metastases in a Patient With Crossed Fused Renal Ectopia.Clin Nucl Med. 2019 Feb;44(2):157-158. doi: 10.1097/RLU.0000000000002390.
10 Alpha1-antichymotrypsin, an inflammatory protein overexpressed in Alzheimer's disease brain, induces tau phosphorylation in neurons.Brain. 2006 Nov;129(Pt 11):3020-34. doi: 10.1093/brain/awl255. Epub 2006 Sep 20.
11 Breast and ovarian cancer referrals to the ACT Genetic Service: are we meeting guidelines?.Intern Med J. 2017 Mar;47(3):311-317. doi: 10.1111/imj.13357.
12 Association between the genetic variations within TBX21 gene promoter and the clinicopathological characteristics of esophageal squamous cell carcinoma in a high-risk Chinese population.Tumour Biol. 2015 May;36(5):3985-93. doi: 10.1007/s13277-015-3042-x. Epub 2015 Jan 11.
13 Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population.Int J Cancer. 2011 Jan 1;128(1):166-75. doi: 10.1002/ijc.25306.
14 Ionizing radiation and TNF-alpha and stimulated expression of alpha1-antichymotrypsin gene in human squamous carcinoma cells.Acta Oncol. 1998;37(5):475-8. doi: 10.1080/028418698430430.
15 Familial hemophagocytic lymphohistiocytosis type 5 in a Chinese Tibetan patient caused by a novel compound heterozygous mutation in STXBP2.Medicine (Baltimore). 2019 Oct;98(43):e17674. doi: 10.1097/MD.0000000000017674.
16 Clinical pharmacology of the dual orexin receptor antagonist ACT-541468 in elderly subjects: Exploration of pharmacokinetics, pharmacodynamics and tolerability following single-dose morning and repeated-dose evening administration.J Psychopharmacol. 2020 Mar;34(3):326-335. doi: 10.1177/0269881119882854. Epub 2019 Oct 23.
17 Mass drug administration can be a valuable addition to the malaria elimination toolbox.Malar J. 2019 Aug 22;18(1):281. doi: 10.1186/s12936-019-2906-8.
18 Using mixed methods case-series evaluation in the development of a guided self-management hybrid CBT and ACT intervention for multiple sclerosis pain.Disabil Rehabil. 2017 Sep;39(18):1785-1798. doi: 10.1080/09638288.2016.1209580. Epub 2016 Aug 24.
19 Effects of l-arginine supplementation associated with continuous or interval aerobic training on chronic heart failure rats.Metabolism. 2017 Nov;76:1-10. doi: 10.1016/j.metabol.2017.06.009. Epub 2017 Jul 5.
20 Bispecific Antibodies Enable Synthetic Agonistic Receptor-Transduced T Cells for Tumor Immunotherapy.Clin Cancer Res. 2019 Oct 1;25(19):5890-5900. doi: 10.1158/1078-0432.CCR-18-3927. Epub 2019 Jul 8.
21 Genetic study of apolipoprotein E gene, alpha-1 antichymotrypsin gene in sporadic Parkinson disease.Am J Med Genet. 2002 May 8;114(4):446-9. doi: 10.1002/ajmg.10249.
22 Membrane Permeabilization by Pore-Forming RTX Toxins: What Kind of Lesions Do These Toxins Form?.Toxins (Basel). 2019 Jun 18;11(6):354. doi: 10.3390/toxins11060354.
23 Outcomes of clients in need of intensive team care in Flexible Assertive Community Treatment in Sweden.Nord J Psychiatry. 2018 Apr;72(3):226-231. doi: 10.1080/08039488.2018.1430168. Epub 2018 Jan 26.
24 Efficacy of tocilizumab monotherapy after response to combined tocilizumab and methotrexate in patients with rheumatoid arthritis: the randomised JUST-ACT study.Clin Exp Rheumatol. 2019 May-Jun;37(3):437-444. Epub 2018 Sep 17.
25 Association of CCL11 promoter polymorphisms with schizophrenia in a Korean population.Gene. 2018 May 20;656:80-85. doi: 10.1016/j.gene.2018.02.053. Epub 2018 Feb 22.
26 Effects of selexipag and its active metabolite in contrasting the profibrotic myofibroblast activity in cultured scleroderma skin fibroblasts.Arthritis Res Ther. 2018 May 2;20(1):77. doi: 10.1186/s13075-018-1577-0.
27 Development of gene therapy with a cyclic adenosine monophosphate response element decoy oligodeoxynucleotide to prevent vascular intimal hyperplasia.J Vasc Surg. 2020 Jan;71(1):229-241. doi: 10.1016/j.jvs.2019.02.042. Epub 2019 Jun 14.
28 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
29 Alpha1-ACT Functions as a Tumour Suppressor in Hepatocellular Carcinoma by Inhibiting the PI3K/AKT/mTOR Signalling Pathway via Activation of PTEN.Cell Physiol Biochem. 2017;41(6):2289-2306. doi: 10.1159/000475648. Epub 2017 Apr 26.
30 Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations.JCI Insight. 2017 Jul 20;2(14):e94564. doi: 10.1172/jci.insight.94564. eCollection 2017 Jul 20.
31 No abnormalities of reg1 alpha and reg1 beta gene associated with diabetes mellitus.Diabetes Res Clin Pract. 2002 Feb;55(2):105-11. doi: 10.1016/s0168-8227(01)00321-7.
32 Adrenocortical carcinoma -- improving patient care by establishing new structures.Exp Clin Endocrinol Diabetes. 2006 Feb;114(2):45-51. doi: 10.1055/s-2006-923808.
33 A Pragmatic Trial of Symptom-Based Inhaled Corticosteroid Use in African-American Children with Mild Asthma.J Allergy Clin Immunol Pract. 2020 Jan;8(1):176-185.e2. doi: 10.1016/j.jaip.2019.06.030. Epub 2019 Jul 30.
34 COPD patients prescribed inhaled corticosteroid in general practice: Based on disease characteristics according to guidelines?.Chron Respir Dis. 2019 Jan-Dec;16:1479973119867949. doi: 10.1177/1479973119867949.
35 Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene.Diabetes. 1998 Apr;47(4):598-605. doi: 10.2337/diabetes.47.4.598.
36 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
37 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.
38 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.