Property Summary

NCBI Gene PubMed Count 68
PubMed Score 183.40
PubTator Score 125.75

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma -6.702 1.5e-08
group 3 medulloblastoma 2.300 2.1e-04
psoriasis 1.100 3.1e-03

Gene RIF (56)

PMID Text
26903544 a broad range of hitherto unrelated human red cell disorders are caused by variants in KLF1, a master regulator of erythropoiesis, which were previously considered to be extremely rare causes of human genetic disease [review]
26840243 results suggest that KLF1 directly regulates the beta-globin gene, but probably has less direct impact on expression of the gamma-globin gene in fetal erythroblasts
26303528 The study identified the DEK oncoprotein as a critical factor that interacts with an essential upstream enhancer element of the EKLF promoter and exerts a positive effect on EKLF levels.
26159733 erythrocyte lineage enforces exclusivity through upregulation of EKLF and its lineage-specific cytokine receptor (EpoR) while inhibiting both FLI-1 and the receptor TpoR (also known as MPL) for the opposing megakaryocyte lineage
26053062 a successful induction of gamma-globin includes a reduction in BCL11A, KLF1 and TAL1 expression.
25976964 Studies indicate that Kruppel-like factor 1 (KLF1) mutations have been associated with severe hematologic disorders.
25724378 Described is a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human.
25694242 KLF1 mutations are associated with increased hemoglobin F and A2 expression.
25690802 Here we describe a Japanese patient with mild beta-thalassemia with an intact beta-globin gene but a new missense mutation of c.947G > A or p.C316Y in the KLF1 gene which is strongly associated with the expression of the beta-globin gene.
25585695 A KLF1-targeted promoter-reporter assay showed that the two mutations reduce the expression of the HBB, BCL11A, and CD44 genes involved in erythropoiesis.
25583416 The patient with the p.F182L variant (KLF1: c.544T > C) had noticeably high Hb A2 levels (7.6%), consistent with the phenotypic effect of several previously characterized KLF1 mutations in the same exonic region.
25528728 These results indicate that KLF1 plays a role in facilitating and/or stabilizing GATA-1 and TAL1 occupancy in the erythroid genes, contributing to the generation of active chromatin structure such as histone acetylation and chromatin looping
25457384 SCF-mediated gamma-globin gene expression in adult human erythroid cells is associated with KLF1, BCL11A and SOX6 down-regulation.
24916507 expression of erythroid Kruppel-like factor (EKLF) precedes PlGF, and its enforced expression in erythroid progenitor cells induces PlGF mRNA
24857170 Molecular defect in the alpha-globin and beta-globin genes, and in the KLF1 gene were found in the borderline hemoglobin A2 Chinese individuals.
24829204 findings suggest that KLF1 mutations occur selectively in the presence of beta-thalassemia to increase the production of HbF, which in turn ameliorates the clinical severity of beta-thalassemia.
24711040 The frequency of rare Lu(a-b-) blood group in Shanghai was approximately 0.02%, and all the individuals had an In(Lu) phenotype. The molecular basis of such samples may be related to mutations in the EKLF/KLF1 gene.
24594363 In erythroid cells, pull down experiments identified the presence of a novel complex formed by HDAC5, GATA1, EKLF and pERK which was instead undetectable in cells of the megakaryocytic lineage.
24443441 Mutations in Kruppel-like factor 1 cause transfusion-dependent hemolytic anemia and persistence of embryonic globin gene expression.
24139988 Select activation-degradation regions like the ones found in EKLF and SREBP1a function in part through their ability to form noncovalent interactions with ubiquitin.
23806141 Data suggest that the Kruppel-like factor 1 (KLF) mutations could be one of the causes of hereditary persistence of fetal hemoglobin (HPFH) in regions where thalassemias are common.
23474875 KLF1 conscripts the adult-stage beta-globin gene to replace the gamma-globin gene within the active chromatin hub in a stage-specific manner.
23223429 Simvastatin and tBHQ suppress KLF1 and BCL11 gene expression and additively increase fetal hemoglobin in primary human erythroid cells.
23209159 Regulators, including BCL11A, MYB, and KLF1, hold great promise to develop targeted and more effective approaches for HbF induction
23161389 The 1st KLF1 gene promoter mutation (KLF1:g.-148G > A) associated with increased HbF resides in an Sp1 binding site & prevents Sp1 binding. It is involved in human fetal globin gene switching.
23125034 Data show that KLF1 haploinsufficiency is responsible for the In(Lu) blood type.
22965552 EKLF mRNA level was significantly decreased in the blood and bone marrow of 5q- syndrome and in all Diamond-Blackfan anemia patients.
22393050 Studies show that Ppm1b plays a multilayered role in regulating the availability and optimal activity of the EKLF protein in erythroid cells.
22102705 KLF1 mutations could make a significant contribution to Hb F variance in malarial regions where hemogobinopathies are common. A single altered KLF1 allele is sufficient to increase Hb F levels.
22093801 Mutated KLF1 results in delayed fetal hemoglobin switching in humans, confirming previous in vitro and animal studies and the crucial role of KLF1 in regulating globin gene expression.
21821711 Six different KLF1 mutations were identified in 52 of 145 subjects with borderline HBA2 and normal mean corpuscular volume and mean corpuscular hemoglobin.
21778342 E325K protein may therefore actively interfere with EKLF-dependent processes by destabilizing transcription complexes, providing a rational explanation for the severity of the disease phenotype.
21670263 solution structure of the EKLFTAD2/Tfb1PH complex indicates that EKLFTAD2 binds Tfb1PH in an extended conformation, which is in contrast to the alpha-helical conformation seen for p53TAD2 in complex with Tfb1PH
21610079 KLF1 and KLF2 positively regulate the embryonic and fetal beta-globin genes through direct promoter binding.
21273267 Data show that the association of KLF1 mutations with very high levels of zinc protoporphyrin.
21190291 KLF1 Directly Coordinates Almost All Aspects of Terminal Erythroid Differentiation.
21157349 KLF1, a vital erythroid transcription factor, activates BCL11A and assists in coordinating the switch from fetal to adult hemoglobin
21055716 the study of this disease-causing mutation in KLF1 provides further insights into the roles of this transcription factor during erythropoiesis in humans.
20686118 Overexpression of either KLF1 or LMO2 partially rescued the defect in erythropoiesis caused by c-myb silencing, whereas only KLF1 was also able to repress the megakaryocyte differentiation enhanced in Myb-silenced CD34+ cells.
20676099 Haploinsufficiency for KLF1 causes hereditary persistence of fetal hemoglobin.
20676097 KLF1 controls globin gene switching by directly activating beta-globin and indirectly repressing gamma-globin gene expression.
20642331 Results indicate that detailed analysis of the distribution of the HBB gene mutations is useful for genetic counseling in the region.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19850899 The effect of EKLF on megakaryocyte-erythroid progenitor lineage decision and commitment is cell autonomous in bone marrow reconstitution assays where stem cells lacking EKLF favor the megakaryocyte differentiation pathway.
19251649 EKLF directs different modes of tissue-specific transcriptional activation depending on the architecture of its target core promoter.
19220418 EKLF and the co-activator BRG1 are co-opted by short-chain fatty acid derivatives to activate the gamma globin genes
19097174 A higher expression of EKLF was found in secondary AML versus primary AML. Nevertheless, patients expressing EKLF had a longer overall survival and event free survival than those patients that did not express EKLF.
18523154 EKLF restricts megakaryocytic differentiation to the benefit of erythrocytic differentiation and suggest that this might be at least partially mediated by the inhibition of FLI-1 recruitment to megakaryocytic and Fli-1 gene promoters.
18487511 A search for mutations in erythroid transcription factors showed mutations in the promoter or coding sequence of EKLF in 21 of 24 persons with the In(Lu) phenotype.
18329016 These studies suggest there is an unexplored role for EKLF in the cytoplasm that is separate from its well-characterized nuclear function.
18195733 Sp1/Sp3, but not EKLF, is involved in the activation of the GATA-1 erythroid promoter, and that histones H3 and H4 are highly acetylated in this promoter region for an actively transcribed GATA-1
16858401 Our results further indicate that in hematopoietic progenitors, EKLF influences chromatin organization at the human beta-globin locus and is instrumental for human beta-gene potentiation
16184297 Erythroid Kruppel-like factor (EKLF; KLF1) is a transcription factor, originally identified in this laboratory, which plays a crucial role as a transcriptional activator at the adult beta-globin locus.
15937668 Observational study of gene-disease association. (HuGE Navigator)
14976188 bifunctional control of IL-12 p40 by EKLF and its modulation of NFkappaB support a potential function for this factor in orchestrating IL-12 p40 production in macrophages
11844803 nuclear localization determinants of EKLF depend on basic residues with the Kruppel zinc finter dna binding domains

AA Sequence

MATAETALPSISTLTALGPFPDTQDDFLKWWRSEEAQDMGPGPPDPTEPPLHVKSEDQPGEEEDDERGAD      1 - 70
ATWDLDLLLTNFSGPEPGGAPQTCALAPSEASGAQYPPPPETLGAYAGGPGLVAGLLGSEDHSGWVRPAL     71 - 140
RARAPDAFVGPALAPAPAPEPKALALQPVYPGPGAGSSGGYFPRTGLSVPAASGAPYGLLSGYPAMYPAP    141 - 210
QYQGHFQLFRGLQGPAPGPATSPSFLSCLGPGTVGTGLGGTAEDPGVIAETAPSKRGRRSWARKRQAAHT    211 - 280
CAHPGCGKSYTKSSHLKAHLRTHTGEKPYACTWEGCGWRFARSDELTRHYRKHTGQRPFRCQLCPRAFSR    281 - 350
SDHLALHMKRHL                                                              351 - 362
//

Text Mined References (70)

PMID Year Title
26903544 2016 Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants.
26840243 2016 Krüppel-Like Transcription Factor KLF1 Is Required for Optimal ?- and ?-Globin Expression in Human Fetal Erythroblasts.
26303528 2015 The DEK Oncoprotein Is a Critical Component of the EKLF/KLF1 Enhancer in Erythroid Cells.
26159733 2015 Robust hematopoietic progenitor cell commitment in the presence of a conflicting cue.
26053062 2015 Variation in Gamma-Globin Expression before and after Induction with Hydroxyurea Associated with BCL11A, KLF1 and TAL1.
25976964 2015 Krüppel-like factor 1: hematologic phenotypes associated with KLF1 gene mutations.
25724378 2015 KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.
25694242 2015 Krüppel-like factor 1 mutations and expression of hemoglobins F and A2 in homozygous hemoglobin E syndrome.
25690802 2015 A new Krüppel-like factor 1 mutation (c.947G?>?A or p.C316Y) in humans causes ?-thalassemia minor.
25585695 2015 Compound heterozygosity for KLF1 mutations is associated with microcytic hypochromic anemia and increased fetal hemoglobin.
25583416 2015 Mutation screening of the Krüppel-like factor 1 gene using single-strand conformational polymorphism in a cohort of Iranian ?-thalassemia patients.
25528728 2015 KLF1 stabilizes GATA-1 and TAL1 occupancy in the human ?-globin locus.
25457384 2015 SCF-mediated ?-globin gene expression in adult human erythroid cells is associated with KLF1, BCL11A and SOX6 down-regulation.
25187353 2014 Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.
24916507 2014 Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.
24857170 2014 Delineation of the molecular basis of borderline hemoglobin A2 in Chinese individuals.
24829204 2014 KLF1 mutations are relatively more common in a thalassemia endemic region and ameliorate the severity of ?-thalassemia.
24711040 2014 [Screening of rare blood group Lu(a-b-) phenotype and study of its molecular basis in ethnic Han Chinese from Shanghai region].
24594363 2014 Identification of NuRSERY, a new functional HDAC complex composed by HDAC5, GATA1, EKLF and pERK present in human erythroid cells.
24443441 2014 Mutations in Kruppel-like factor 1 cause transfusion-dependent hemolytic anemia and persistence of embryonic globin gene expression.
24139988 2013 Structural characterization of a noncovalent complex between ubiquitin and the transactivation domain of the erythroid-specific factor EKLF.
23806141 2013 KLF1 gene mutations in Chinese adults with increased fetal hemoglobin.
23474875 2013 Three fingers on the switch: Krüppel-like factor 1 regulation of ?-globin to ?-globin gene switching.
23223429 2013 Simvastatin and t-butylhydroquinone suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells.
23209159 2013 The switch from fetal to adult hemoglobin.
23161389 2013 Functional analysis of a novel KLF1 gene promoter variation associated with hereditary persistence of fetal hemoglobin.
23125034 2013 Molecular analysis of the rare in(Lu) blood type: toward decoding the phenotypic outcome of haploinsufficiency for the transcription factor KLF1.
22965552 2013 Transcription factors Fli1 and EKLF in the differentiation of megakaryocytic and erythroid progenitor in 5q- syndrome and in Diamond-Blackfan anemia.
22393050 2012 Functional interactions between erythroid Krüppel-like factor (EKLF/KLF1) and protein phosphatase PPM1B/PP2C?.
22102705 2012 Ten novel mutations in the erythroid transcription factor KLF1 gene associated with increased fetal hemoglobin levels in adults.
22093801 2012 Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation.
21821711 2011 KLF1 gene mutations cause borderline HbA(2).
21778342 2011 Mutations in the second zinc finger of human EKLF reduce promoter affinity but give rise to benign and disease phenotypes.
21670263 2011 Structural and functional characterization of an atypical activation domain in erythroid Kruppel-like factor (EKLF).
21610079 2011 Transcription factors KLF1 and KLF2 positively regulate embryonic and fetal beta-globin genes through direct promoter binding.
21539536 2011 Krüppel-like Factor 4 activates HBG gene expression in primary erythroid cells.
21273267 2011 Compound heterozygosity for KLF1 mutations associated with remarkable increase of fetal hemoglobin and red cell protoporphyrin.
21190291 2010 KLF1 directly coordinates almost all aspects of terminal erythroid differentiation.
21157349 2011 Update on fetal hemoglobin gene regulation in hemoglobinopathies.
21055716 2010 A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia.
20686118 2010 c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression.
20676099 2010 Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin.
20676097 2010 KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching.
20642331 2010 Region-specific genetic heterogeneity of HBB mutation distribution in South-Western Greece.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
19850899 2010 Megakaryocyte-erythroid lineage promiscuity in EKLF null mouse blood.
19251649 2009 Distinct modes of gene regulation by a cell-specific transcriptional activator.
19220418 2009 Erythroid Kruppel-like factor (EKLF) is recruited to the gamma-globin gene promoter as a co-activator and is required for gamma-globin gene induction by short-chain fatty acid derivatives.
19097174 2009 Clinical significance of Gata-1, Gata-2, EKLF, and c-MPL expression in acute myeloid leukemia.
18523154 2008 EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation.
18487511 2008 Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype.
18329016 2008 Non-random subcellular distribution of variant EKLF in erythroid cells.
18195733 2008 Involvement of Sp1/Sp3 in the activation of the GATA-1 erythroid promoter in K562 cells.
16858401 2006 Lineage-specific activators affect beta-globin locus chromatin in multipotent hematopoietic progenitors.
16184297 2005 Probing the onset and regulation of erythroid cell-specific gene expression.
15937668 2005 Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15057824 2004 The DNA sequence and biology of human chromosome 19.
14976188 2004 Activation and repression of interleukin-12 p40 transcription by erythroid Kruppel-like factor in macrophages.
12556498 2003 Functional cross-antagonism between transcription factors FLI-1 and EKLF.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12072445 2002 Krüppel-like zinc fingers bind to nuclear import proteins and are required for efficient nuclear localization of erythroid Krüppel-like factor.
11259590 2001 Site-specific acetylation by p300 or CREB binding protein regulates erythroid Krüppel-like factor transcriptional activity via its interaction with the SWI-SNF complex.
11018012 2000 Functional selectivity of recombinant mammalian SWI/SNF subunits.
9778250 1998 A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue-specific transcriptional regulation by EKLF in vitro.
9722526 1998 Regulation of erythroid Krüppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain.
9707565 1998 Acetylation and modulation of erythroid Krüppel-like factor (EKLF) activity by interaction with histone acetyltransferases.
9119377 1997 The human erythroid-specific transcription factor EKLF localizes to chromosome 19p13.12-p13.13.
8924208 1996 Isolation, genomic structure, and expression of human erythroid Krüppel-like factor (EKLF).
7753194 1995 Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene.