Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT72R16T)

DOT Name Complement factor H-related protein 1 (CFHR1)
Synonyms FHR-1; H factor-like protein 1; FHL-1; H-factor-like 1; H36
Gene Name CFHR1
Related Disease
IgA nephropathy ( )
3-hydroxyacyl-CoA dehydrogenase deficiency ( )
Advanced cancer ( )
Autosomal dominant polycystic kidney disease ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Hemolytic-uremic syndrome ( )
Hepatocellular carcinoma ( )
Liver cirrhosis ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lupus ( )
Neoplasm ( )
Neuromyelitis optica ( )
Non-immunoglobulin-mediated membranoproliferative glomerulonephritis ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Pneumonia ( )
Pneumonitis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Pulmonary fibrosis ( )
Systemic lupus erythematosus ( )
Thrombotic microangiopathy ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Age-related macular degeneration ( )
Breast cancer ( )
Breast carcinoma ( )
Chronic obstructive pulmonary disease ( )
Colon adenocarcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal adenocarcinoma ( )
Graft-versus-host disease ( )
High blood pressure ( )
Dense deposit disease ( )
Neural tube defect ( )
Thrombotic thrombocytopenic purpura ( )
Acute myelogenous leukaemia ( )
Age related macular degeneration 1 ( )
Chronic renal failure ( )
End-stage renal disease ( )
Follicular lymphoma ( )
Hemolytic uremic syndrome, atypical, susceptibility to, 1 ( )
Meningococcal disease ( )
Nephropathy ( )
UniProt ID
FHR1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3ZD2; 4MUC
Pfam ID
PF00084
Sequence
MWLLVSVILISRISSVGGEATFCDFPKINHGILYDEEKYKPFSQVPTGEVFYYSCEYNFV
SPSKSFWTRITCTEEGWSPTPKCLRLCFFPFVENGHSESSGQTHLEGDTVQIICNTGYRL
QNNENNISCVERGWSTPPKCRSTDTSCVNPPTVQNAHILSRQMSKYPSGERVRYECRSPY
EMFGDEEVMCLNGNWTEPPQCKDSTGKCGPPPPIDNGDITSFPLSVYAPASSVEYQCQNL
YQLEGNKRITCRNGQWSEPPKCLHPCVISREIMENYNIALRWTAKQKLYLRTGESAEFVC
KRGYRLSSRSHTLRTTCWDGKLEYPTCAKR
Function
Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH. Can associate with lipoproteins and may play a role in lipid metabolism.
Tissue Specificity Expressed by the liver and secreted in plasma.
KEGG Pathway
Complement and coagulation cascades (hsa04610 )
Reactome Pathway
Regulation of Complement cascade (R-HSA-977606 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
IgA nephropathy DISZ8MTK Definitive Biomarker [1]
3-hydroxyacyl-CoA dehydrogenase deficiency DISBJ31P Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Autosomal dominant polycystic kidney disease DISBHWUI Strong Genetic Variation [1]
Bladder cancer DISUHNM0 Strong Biomarker [4]
Bone osteosarcoma DIST1004 Strong Biomarker [5]
Hemolytic-uremic syndrome DISSCBGW Strong Genetic Variation [6]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [3]
Liver cirrhosis DIS4G1GX Strong Altered Expression [3]
Lung adenocarcinoma DISD51WR Strong Biomarker [7]
Lung cancer DISCM4YA Strong Biomarker [7]
Lupus DISOKJWA Strong Genetic Variation [8]
Neoplasm DISZKGEW Strong Genetic Variation [9]
Neuromyelitis optica DISBFGKL Strong Biomarker [10]
Non-immunoglobulin-mediated membranoproliferative glomerulonephritis DISLMV1J Strong Genetic Variation [11]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [12]
Osteosarcoma DISLQ7E2 Strong Biomarker [5]
Pneumonia DIS8EF3M Strong Biomarker [13]
Pneumonitis DIS88E0K Strong Biomarker [13]
Prostate cancer DISF190Y Strong Biomarker [14]
Prostate carcinoma DISMJPLE Strong Biomarker [14]
Pulmonary fibrosis DISQKVLA Strong Biomarker [15]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [8]
Thrombotic microangiopathy DISLZ0VW Strong Genetic Variation [16]
Urinary bladder cancer DISDV4T7 Strong Biomarker [4]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [4]
Age-related macular degeneration DIS0XS2C moderate Genetic Variation [17]
Breast cancer DIS7DPX1 moderate Biomarker [14]
Breast carcinoma DIS2UE88 moderate Biomarker [14]
Chronic obstructive pulmonary disease DISQCIRF moderate Altered Expression [18]
Colon adenocarcinoma DISDRE0J moderate Biomarker [14]
Colon cancer DISVC52G moderate Biomarker [14]
Colon carcinoma DISJYKUO moderate Biomarker [14]
Colorectal adenocarcinoma DISPQOUB moderate Biomarker [14]
Graft-versus-host disease DIS0QADF moderate Biomarker [19]
High blood pressure DISY2OHH moderate Genetic Variation [20]
Dense deposit disease DISLWJSE Supportive Autosomal recessive [21]
Neural tube defect DIS5J95E Disputed Genetic Variation [22]
Thrombotic thrombocytopenic purpura DIS3LDOU Disputed Biomarker [23]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [24]
Age related macular degeneration 1 DISJSM4U Limited Unknown [25]
Chronic renal failure DISGG7K6 Limited Genetic Variation [26]
End-stage renal disease DISXA7GG Limited Genetic Variation [26]
Follicular lymphoma DISVEUR6 Limited Biomarker [27]
Hemolytic uremic syndrome, atypical, susceptibility to, 1 DIS5NG8S Limited Unknown [28]
Meningococcal disease DISGDM2Z Limited Genetic Variation [29]
Nephropathy DISXWP4P Limited Biomarker [30]
------------------------------------------------------------------------------------
⏷ 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 Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Complement factor H-related protein 1 (CFHR1). [31]
------------------------------------------------------------------------------------
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Complement factor H-related protein 1 (CFHR1). [32]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Complement factor H-related protein 1 (CFHR1). [33]
Progesterone DMUY35B Approved Progesterone increases the expression of Complement factor H-related protein 1 (CFHR1). [34]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Complement factor H-related protein 1 (CFHR1). [35]
------------------------------------------------------------------------------------

References

1 Elevated factor H-related protein 1 and factor H pathogenic variants decrease complement regulation inIgA nephropathy.Kidney Int. 2017 Oct;92(4):953-963. doi: 10.1016/j.kint.2017.03.041. Epub 2017 Jun 19.
2 Indications of underdiagnosis of atypical haemolytic uraemic syndrome in a cohort referred to the Coagulation Unit in Malmo, Sweden, for analysis of ADAMTS13 2007-2012.Nephrology (Carlton). 2017 Jul;22(7):555-561. doi: 10.1111/nep.12818.
3 Downregulated expression of CFHL1 is associated with unfavorable prognosis in postoperative patients with hepatocellular carcinoma.Exp Ther Med. 2019 May;17(5):4073-4079. doi: 10.3892/etm.2019.7455. Epub 2019 Mar 29.
4 Electrochemical ELISA-based platform for bladder cancer protein biomarker detection in urine.Biosens Bioelectron. 2018 Oct 15;117:620-627. doi: 10.1016/j.bios.2018.07.003. Epub 2018 Jul 3.
5 Construction of a novel oncolytic adenoviral vector and its biological characteristics.Oncol Rep. 2013 Feb;29(2):798-804. doi: 10.3892/or.2012.2140. Epub 2012 Nov 15.
6 Atypical presentation of atypical haemolytic uraemic syndrome.BMJ Case Rep. 2018 Feb 11;2018:bcr2017222560. doi: 10.1136/bcr-2017-222560.
7 CFHR1 is a potentially downregulated gene in lung adenocarcinoma.Mol Med Rep. 2019 Oct;20(4):3642-3648. doi: 10.3892/mmr.2019.10644. Epub 2019 Sep 3.
8 Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review.Clin Rheumatol. 2017 Dec;36(12):2859-2867. doi: 10.1007/s10067-017-3823-2. Epub 2017 Sep 13.
9 CDK1 inhibition sensitizes normal cells to DNA damage in a cell cycle dependent manner.Cell Cycle. 2018;17(12):1513-1523. doi: 10.1080/15384101.2018.1491236. Epub 2018 Jul 25.
10 CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders.J Immunol. 2016 Nov 1;197(9):3471-3480. doi: 10.4049/jimmunol.1600135. Epub 2016 Sep 26.
11 A novel CFHR1-CFHR5 hybrid leads to a familial dominant C3 glomerulopathy.Kidney Int. 2017 Oct;92(4):876-887. doi: 10.1016/j.kint.2017.04.025. Epub 2017 Jul 18.
12 Hepatocyte growth factor produced in lung fibroblasts enhances non-small cell lung cancer cell survival and tumor progression.Respir Res. 2017 Jun 15;18(1):118. doi: 10.1186/s12931-017-0604-z.
13 Specific regulation of PRMT1 expression by PIAS1 and RKIP in BEAS-2B epithelia cells and HFL-1 fibroblasts in lung inflammation.Sci Rep. 2016 Feb 25;6:21810. doi: 10.1038/srep21810.
14 Design and synthesis of substituted dihydropyrimidinone derivatives as cytotoxic and tubulin polymerization inhibitors.Bioorg Chem. 2019 Dec;93:103317. doi: 10.1016/j.bioorg.2019.103317. Epub 2019 Sep 26.
15 Triptolide protects against TGF-1-induced pulmonary fibrosis by regulating FAK/calpain signaling.Exp Ther Med. 2019 Dec;18(6):4781-4789. doi: 10.3892/etm.2019.8127. Epub 2019 Oct 25.
16 A Heterozygous CFHR3-CFHR1 Gene Deletion in a Pediatric Patient With Transplant-associated Thrombotic Microangiopathy Who was Treated With Eculizumab.J Pediatr Hematol Oncol. 2018 Nov;40(8):e544-e546. doi: 10.1097/MPH.0000000000000986.
17 miRNAs, single nucleotide polymorphisms (SNPs) and age-related macular degeneration (AMD).Clin Chem Lab Med. 2017 May 1;55(5):763-775. doi: 10.1515/cclm-2016-0898.
18 miR-483-5p plays a protective role in chronic obstructive pulmonary disease.Int J Mol Med. 2017 Jul;40(1):193-200. doi: 10.3892/ijmm.2017.2996. Epub 2017 May 18.
19 Copy number polymorphisms in new HapMap III and Singapore populations.J Hum Genet. 2011 Aug;56(8):552-60. doi: 10.1038/jhg.2011.54. Epub 2011 Jun 16.
20 Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure and hypertension in Chinese population.PLoS One. 2012;7(7):e42010. doi: 10.1371/journal.pone.0042010. Epub 2012 Jul 25.
21 C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. J Clin Invest. 2013 Jun;123(6):2434-46. doi: 10.1172/JCI68280.
22 The C677T polymorphism of the methylenetetrahydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations.Ann Genet. 2000 Apr-Jun;43(2):89-92. doi: 10.1016/s0003-3995(00)90012-1.
23 Autoimmune forms of thrombotic microangiopathy and membranoproliferative glomerulonephritis: Indications for a disease spectrum and common pathogenic principles.Mol Immunol. 2009 Sep;46(14):2801-7. doi: 10.1016/j.molimm.2009.05.018. Epub 2009 Jul 28.
24 Coculture of native human acute myelogenous leukemia blasts with fibroblasts and osteoblasts results in an increase of vascular endothelial growth factor levels.Eur J Haematol. 2005 Jan;74(1):24-34. doi: 10.1111/j.1600-0609.2004.00333.x.
25 Complement factor H related proteins (CFHRs). Mol Immunol. 2013 Dec 15;56(3):170-80. doi: 10.1016/j.molimm.2013.06.001. Epub 2013 Jul 3.
26 The autoimmune disease DEAP-hemolytic uremic syndrome.Semin Thromb Hemost. 2010 Sep;36(6):625-32. doi: 10.1055/s-0030-1262884. Epub 2010 Sep 23.
27 Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma.Am J Hematol. 2012 Sep;87(9):880-5. doi: 10.1002/ajh.23273. Epub 2012 Jun 20.
28 Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome. Blood. 2009 Nov 5;114(19):4261-71. doi: 10.1182/blood-2009-05-223834. Epub 2009 Sep 10.
29 Complement factor H, FHR-3 and FHR-1 variants associate in an extended haplotype conferring increased risk of atypical hemolytic uremic syndrome.Mol Immunol. 2015 Oct;67(2 Pt B):276-86. doi: 10.1016/j.molimm.2015.06.021. Epub 2015 Jul 7.
30 The clinical significance of plasma CFHR 1-5 in lupus nephropathy.Immunobiology. 2019 May;224(3):339-346. doi: 10.1016/j.imbio.2019.03.005. Epub 2019 Apr 3.
31 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.
32 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.
33 Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
34 Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
35 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.