F11 (REGN-7508 Biosimilar) Recombinant Monoclonal Antibody

1. Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. PMID: 27723456
2. The aim of the current study was to analyze, for the first time in the Portuguese population, five well known and replicated venous thromboembolism - associated single nucleotide polymorphisms in genes ABO (rs2519093 and rs8176719), F11 (rs2036914 and rs2289252) and FGG (rs2066865), and to determine its possible association with risk for venous thromboembolism. PMID: 29995659
3. Data indicate four new factor XI (FXI) gene defects potentially causing a functional deficiency and the duplication of 1653 bp involving exons 8 and 9. PMID: 28960694
4. In this prospective cohort of elderly adults, there was no statistically significant association of higher FXI levels with incident coronary heart disease and stroke. PMID: 28009647
5. High molecular weight kininogen has an inhibitory effect on nucleic acid-supported fXI activation and may function as a negative regulator of fXI activation. PMID: 28124063
6. FXI has a role in promoting a vascular coagulation-inflammatory circuit in arterial hypertension PMID: 28148841
7. thrombin activatable fibrinolysis inhibitor pathway impairment, largely caused by a hitherto unknown TAFIa resistance, appears to be one main cause of decreased fibrinolytic resistance in FXI deficiency PMID: 27094709
8. factor XI has a role in procoagulant microparticle-promoted coagulation in human endotoxemia PMID: 26857798
9. Three loci showed robust, replicating association with circulating FXI levels: KNG1 (rs710446, P-value = 2.07 x 10-302), F11 (rs4253417, P-value = 2.86 x 10-193), and a novel association in GCKR (rs780094, P-value = 3.56 x10-09), here for the first time implicated in FXI regulation. The two first SNPs (rs710446 and rs4253417) also associated with partial thromboplastin time PMID: 28053049
10. The rs710446 and five low-frequency variant sets in KNG1 with FXI level variation of Factor XI were significant after multiple testing correction and permutation. PMID: 28445521
11. Exploring the global landscape of genetic variation in coagulation factor XI deficiency PMID: 28615222
12. Structures of FXI in complex with the laminin-derived peptide EFPDFP and a DFP peptide from the random screen demonstrated binding in the same pocket, although in a slightly different conformation, thus revealing some flexibility in the molecular interactions of the FXI apple 2 domain. PMID: 27006387
13. inhibition of FXI and FXII distinctly alter the biophysical properties of fibrin. PMID: 27933406
14. Data show that among the studied polymorphisms, only coagulation factor XI (F11) single nucleotide polymorphism rs2289252 was significantly associated with venous thrombosis (VT) and the F11 rs2289252-A allele was associated with a 1.6-fold increased risk of VT PMID: 27414984
15. Thus in conclusion, the bleeding manifestations in FXI deficiency are varied and unpredictable; neither correlates with FXI levels nor with the mutations. Comprehensive analysis of all the factors including both plasma and platelet FXI, global hemostatic factors like thrombin generation potential may indicate a potential laboratory indicator for FXI deficiency related bleeding manifestations. PMID: 27710856
16. Fasudil reduced LPS-mediated TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of fasudil in the treatment of CAPD patients. PMID: 27756191
17. rs2289252 and rs2036914 polymorphisms have important role in development of venous thromboembolism in the white race PMID: 28353616
18. High activity of factor XI indicates a risk of occurrence of deep vein thrombosis in post-trauma patients with fractures. F11 rs2089252 and rs2036914 (single nucleotide polymorphisms) are associated with activity of factors XI in such patients despite prophylaxis. PMID: 27627722
19. this study confirms the significant associations between polymorphism of 25264C.T in FXI and its activity and the risk of deep vein thrombosis after artificial joint replacement surgery PMID: 26934731
20. F11 genetic variants are associated with the risk of incident venous thrombosis among women PMID: 26631918
21. This study characterized FXI deficiency mutation spectrum in Chinese population with a high frequency of the W228*, G400V, Q263* and c.1136-4delGTTG mutations, which is distinct from that of other populations including Korean, Jewish or European populations. PMID: 27067486
22. factor XI is localized to GPIb in membrane rafts and that this association is important for promoting the activation of factor XI by thrombin on the platelet surface PMID: 12517745
23. higher basal factor XI concentration in the general population is not a risk marker for stroke or coronary heart disease PMID: 26386215
24. Factor XI and factor XII activities were significantly higher in patients with slow coronary flow than in controls, and could be associated with enhanced procoagulant state present in these patients. PMID: 24509324
25. FXI-thrombin axis contributes to distal platelet activation and procoagulant microaggregate formation in the blood flow downstream of the site of thrombus formation. PMID: 26769048
26. F11 gene variant rs2289252 contributes to inherited forms of deep vein thrombosis incidence in Latvian population. PMID: 25091233
27. These studies enhance understanding on the first allosteric inhibitor of FXIa and highlight its value as a promising anticoagulant. PMID: 25935648
28. ROTEM assays failed to distinguish bleeding from non-bleeding patients but could do so between different FXI activity levels and genotypes. PMID: 26160656
29. increased activity of FXI may be a potential risk factor for miscarriage; high activity of FXI diagnosed in women with history of miscarriage is not probably caused by the presence of SNPs rs2289252 and rs2036914 PMID: 25517908
30. Data indicate that the mean factor XI (FXI) was not significantly different in laboratories using the same method on both exercises, suggesting good intralaboratory precision over time. PMID: 25976967
31. Identification of a novel c.290G>A mutation in the F11 gene that is associated with mild Factor XI deficiency in a Dutch Caucasian family. PMID: 25618263
32. In whites, the FXI variant was associated with both factor XI concentration and venous thromboembolism (VTE) incidence (1.15-fold greater incidence of VTE per risk allele), whereas In African-Americans, these associations were absent. PMID: 26260105
33. Mass spectrometry analyses of FXI revealed full occupation of two of the three heavy-chain glycosites and almost full-site occupancy of the light chain. Analysis of FXI glycopeptides by LC-MS/MS enabled site-specific glycan profiling and occupancy. PMID: 25092234
34. This study presents the first application of a new thrombin generation based factor XIa assay. PMID: 25288467
35. study determined the molecular basis of FXI deficiency in 6 unrelated severely deficient patients in China; reported 8 mutations in FXI gene leading to FXI deficiency; functional consequences of a novel mutation leading to FXI deficiency have been elucidated PMID: 25681615
36. FXI expression is directly regulated by a specific miRNA, miR-181a-5p, in the human liver PMID: 25379760
37. FXI may have a role in risk of ischemic stroke, but not myocardial infarct; FXII and prekallikrein may not have a role in either PMID: 24977287
38. We suggested that the minor allele of rs3756008 in the promoter of FXI gene could reduce its expression in kidney. PMID: 24420855
39. at variance with other populations, no single major founder effect is present in Italian patients with FXI deficiency. PMID: 24112640
40. Genetic variants of coagulation factor XI show association with ischemic stroke up to 70 years of age. PMID: 24086496
41. Identification of a novel candidate F11 gene mutation associated with a cross-reacting material positive plasma FXI deficiency. PMID: 23571684
42. Studies indicate that in the past two decades, more than 220 mutations in the factor XI (FXI) gene have been reported in patients with FXI deficiency, of which 7 showed a founder effect. PMID: 23929304
43. a novel mutations in family with inherited factor XI deficiency PMID: 23494098
44. Propose that long polyphosphates promote FXII-mediated blood coagulation bypassing FXI. PMID: 23659638
45. The rather rare type I mutation in the FXI gene is a third founder mutation in Ashkenazi Jews with factor XI deficiency. PMID: 23332144
46. For activation by thrombin, or during autoactivation, the data support a cis-activation mechanism in which the activating protease binds to and activates the same fXI subunit. PMID: 23515926
47. F11 gene mutational screening revealed 11 different DNA variations, 3 of which had not yet been described PMID: 23305485
48. Factor XI is a substrate for oxidoreductases: enhanced activation of reduced FXI is found in antiphospholipid syndrome thrombosis. PMID: 22704541
49. A novel amino acid substitution in the serine protease catalytic domain (Ile463Ser) appears to be responsible for the congenital factor XI deficiency in a Swiss family. PMID: 22322133
50. The F11 rs2289252 polymorphism is associated with FXI activity levels and APTT ratio in women with thrombosis. PMID: 22633531

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HGNC: 3529

OMIM: 264900

KEGG: hsa:2160

STRING: 9606.ENSP00000384957

UniGene: Hs.1430