Gene Symbol: LFNG
Description: LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
Alias: SCDO3, beta-1,3-N-acetylglucosaminyltransferase lunatic fringe
Species: human
Products:     LFNG

Top Publications

  1. Kadur Lakshminarasimha Murthy P, Srinivasan T, Bochter M, Xi R, Varanko A, Tung K, et al. Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis. elife. 2018;7: pubmed publisher
    ..Expressed by various secretory cells in the upper crypt and villus, LFNG promotes DLL surface expression and suppresses the secretory lineage ...
  2. Otomo N, Mizumoto S, Lu H, Takeda K, Campos Xavier B, Mittaz Crettol L, et al. Identification of novel LFNG mutations in spondylocostal dysostosis. J Hum Genet. 2019;64:261-264 pubmed publisher
    ..Seven disease genes have been reported as causal genes for SCDO: DLL3, MESP2, TBX6, HES7, RIPPLY2, DMRT2, and LFNG. Here we report a Japanese SCDO case with multiple severe vertebral anomalies from cervical to sacral spine...
  3. Zhang S, Chung W, Wu G, Egan S, Miele L, Xu K. Manic fringe promotes a claudin-low breast cancer phenotype through notch-mediated PIK3CG induction. Cancer Res. 2015;75:1936-43 pubmed publisher
    ..Mfng deletion in the Lfng(flox/flox);MMTV-Cre mouse model, in which one-third of mammary tumors resemble human CLBC, caused a tumor subtype ..
  4. Matsuda M, Koga M, Woltjen K, Nishida E, Ebisuya M. Synthetic lateral inhibition governs cell-type bifurcation with robust ratios. Nat Commun. 2015;6:6195 pubmed publisher
    ..inhibition circuit comprises transcriptional repression of Delta and intracellular feedback of Lunatic fringe (Lfng). The Lfng-feedback subcircuit, even alone, causes the autonomous cell-type bifurcation...
  5. Ferjentsik Z, Hayashi S, Dale J, Bessho Y, Herreman A, De Strooper B, et al. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009;5:e1000662 pubmed publisher
    ..by analysing embryos carrying a mutation in different components of the Notch pathway, such as Lunatic fringe (Lfng), Hes7, Rbpj, and presenilin1/presenilin2 (Psen1/Psen2), and by pharmacological blocking of the Notch pathway...
  6. Serth K, Schuster Gossler K, Kremmer E, Hansen B, Marohn Köhn B, Gossler A. O-fucosylation of DLL3 is required for its function during somitogenesis. PLoS ONE. 2015;10:e0123776 pubmed publisher
    ..somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling...
  7. Hayashi S, Shimoda T, Nakajima M, Tsukada Y, Sakumura Y, Dale J, et al. Sprouty4, an FGF inhibitor, displays cyclic gene expression under the control of the notch segmentation clock in the mouse PSM. PLoS ONE. 2009;4:e5603 pubmed publisher
  8. Bone R, Bailey C, Wiedermann G, Ferjentsik Z, Appleton P, Murray P, et al. Spatiotemporal oscillations of Notch1, Dll1 and NICD are coordinated across the mouse PSM. Development. 2014;141:4806-16 pubmed publisher
    ..of Dll1 and Notch1, and show they are highly correlated with the expression patterns of two known clock components [Lfng mRNA and the activated form of the Notch receptor (cleaved Notch intracellular domain, NICD)]...
  9. Willet C, Makara M, Reppas G, Tsoukalas G, Malik R, Haase B, et al. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs. PLoS ONE. 2015;10:e0117055 pubmed publisher
    ..Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect...

More Information


  1. Achilleos A, Huffman N, Marcinkiewicyz E, Seidah N, Chen Q, Dallas S, et al. MBTPS1/SKI-1/S1P proprotein convertase is required for ECM signaling and axial elongation during somitogenesis and vertebral development†. Hum Mol Genet. 2015;24:2884-98 pubmed publisher
    ..to (i) maintain the Fgf8 'wavefront' in the presomitic mesoderm that underpins axial elongation, (ii) sustain the Lfng oscillatory 'clock' activity that governs the periodicity of somite formation and (iii) preserve the composition ..
  2. McInerney Leo A, Sparrow D, Harris J, Gardiner B, Marshall M, O Reilly V, et al. Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects. Hum Mol Genet. 2015;24:1234-42 pubmed publisher
    ..in several genes involved in the Notch pathway are associated with SDV, with both autosomal recessive (MESP2, DLL3, LFNG, HES7) and autosomal dominant (TBX6) inheritance...
  3. Song Y, Kumar V, Wei H, Qiu J, Stanley P. Lunatic, Manic, and Radical Fringe Each Promote T and B Cell Development. J Immunol. 2016;196:232-43 pubmed publisher
    Lunatic, Manic, and Radical Fringe (LFNG, MFNG, and RFNG) are N-acetylglucosaminyltransferases that modify Notch receptors and regulate Notch signaling...
  4. Schmitz Rohmer D, Probst S, Yang Z, Laurent F, Stadler M, Zuniga A, et al. NDR Kinases Are Essential for Somitogenesis and Cardiac Looping during Mouse Embryonic Development. PLoS ONE. 2015;10:e0136566 pubmed publisher
    ..Ndr1/2-double null embryos show defects in somitogenesis and cardiac looping, which reveals their essential functions and shows that the NDR kinases are critically required during the early phase of organogenesis. ..
  5. Derada Troletti C, Lopes Pinheiro M, Charabati M, Gowing E, Van het Hof B, van der Pol S, et al. Notch signaling is impaired during inflammation in a Lunatic Fringe-dependent manner. Brain Behav Immun. 2018;69:48-56 pubmed publisher
    ..we provide evidence that inflammation reduced the expression of the glycosyltransferase Lunatic Fringe (LFNG), a known positive regulator of Notch glycosylation and signaling, thereby leading to disrupted barrier function of ..
  6. Warrier S, Nuwayhid S, Sabatino J, Sugrue K, Zohn I. Supt20 is required for development of the axial skeleton. Dev Biol. 2017;421:245-257 pubmed publisher
    ..While cycling of Notch target genes in the posterior presomitic mesoderm (PSM) appeared normal, expression of Lfng was reduced...
  7. Wahi K, Friesen S, Coppola V, Cole S. Putative binding sites for mir-125 family miRNAs in the mouse Lfng 3'UTR affect transcript expression in the segmentation clock, but mir-125a-5p is dispensable for normal somitogenesis. Dev Dyn. 2017;246:740-748 pubmed publisher
    In vertebrate embryos, a "segmentation clock" times somitogenesis. Clock-linked genes, including Lunatic fringe (Lfng), exhibit cyclic expression in the presomitic mesoderm (PSM), with a period matching the rate of somite formation...
  8. Onai T, Aramaki T, Inomata H, Hirai T, Kuratani S. On the origin of vertebrate somites. Zoological Lett. 2015;1:33 pubmed publisher
    ..boundary is determined by Notch signalling and the antagonistic relationship of the downstream targets of Notch, Lfng, and Delta1 in the anterior PSM...
  9. Wang H, Jiang Z, Zhang J, Xie Z, Wang Y, Yang G. Enhanced osteogenic differentiation of rat bone marrow mesenchymal stem cells on titanium substrates by inhibiting Notch3. Arch Oral Biol. 2017;80:34-40 pubmed publisher
    ..which included up-regulated genes (Notch2, Dll1, Dll3, Ncstn, Ncor2, and Hes5) and down-regulated genes (Notch3, Lfng, Mfng, Jag2 and Maml2)...
  10. Williams D, Shifley E, Braunreiter K, Cole S. Disruption of somitogenesis by a novel dominant allele of Lfng suggests important roles for protein processing and secretion. Development. 2016;143:822-30 pubmed publisher
    ..In mice, lunatic fringe (Lfng) expression oscillates, and LFNG protein contributes to periodic repression of Notch signaling...
  11. Figueiredo M, Silva J, Santos A, Proa V, Alcobia I, Zilhão R, et al. Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation. Dev Biol. 2016;418:268-82 pubmed publisher
    ..When Hh signalling was abolished, we observed a reduction in the Gata3/Gcm2- and Lfng-expression domains at the median/anterior and median/posterior territories of the pouches, respectively...
  12. Casaca A, Nóvoa A, Mallo M. Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity. Development. 2016;143:437-48 pubmed publisher
    ..In particular, Hoxb6 can disturb somitogenesis and anterior-posterior somite patterning by dysregulation of Lfng expression...
  13. Semerci F, Choi W, Bajić A, Thakkar A, Encinas J, Depreux F, et al. Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance. elife. 2017;6: pubmed publisher
    ..Notch signaling plays a key role during this process. Here, we report that Lunatic fringe (Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs...
  14. Basch M, Brown R, Jen H, Semerci F, Depreux F, Edlund R, et al. Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates. elife. 2016;5: pubmed publisher
    ..We show that two Notch modifiers, Lfng and Mfng, are transiently expressed precisely at the neural boundary of the organ of Corti...
  15. Hahn K, Beres B, Rowton M, Skinner M, Chang Y, Rawls A, et al. A deficiency of lunatic fringe is associated with cystic dilation of the rete testis. Reproduction. 2009;137:79-93 pubmed publisher
    ..Further, the dye studies demonstrated that many lunatic fringe mutant males had partial blocks of the connection between the rete testis and the efferent ducts bilaterally. ..
  16. Raimo M, Orso F, Grassi E, Cimino D, Penna E, De Pittà C, et al. miR-146a Exerts Differential Effects on Melanoma Growth and Metastatization. Mol Cancer Res. 2016;14:548-62 pubmed publisher
    ..It was determined that miR-146a coordinated melanoma cell growth by its direct targets lunatic fringe (LFNG) and NUMB, which operate on the NOTCH/PTEN/Akt pathway; while inhibition of metastasis formation was linked to ..
  17. Lee J, Katzenmaier E, Kopitz J, Gebert J. Reconstitution of TGFBR2 in HCT116 colorectal cancer cells causes increased LFNG expression and enhanced N-acetyl-d-glucosamine incorporation into Notch1. Cell Signal. 2016;28:1105-13 pubmed publisher
    ..array of about 1000 human glycosylation-related genes, several candidates including HES1, PDGFB, JUNB and LFNG were found to be upregulated in a TGFBR2-dependent manner and subsequently validated by real-time RT-PCR analyses...
  18. Chung W, Zhang S, Challagundla L, Zhou Y, Xu K. Lunatic Fringe and p53 Cooperatively Suppress Mesenchymal Stem-Like Breast Cancer. Neoplasia. 2017;19:885-895 pubmed publisher
    ..We previously discovered that deletion of a Notch signaling modulator, Lunatic Fringe (Lfng), in the mouse mammary gland induced a subset of tumors resembling CLBC...
  19. Johnston S, Rauskolb C, Wilson R, Prabhakaran B, Irvine K, Vogt T. A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway. Development. 1997;124:2245-54 pubmed
    ..When misexpressed in the developing Drosophila wing imaginal disc the mouse Fringe genes exhibit conserved and differential effects on boundary determination. ..
  20. Zhang S, Chung W, Xu K. Lunatic Fringe is a potent tumor suppressor in Kras-initiated pancreatic cancer. Oncogene. 2016;35:2485-95 pubmed publisher
    ..Here we report differential regulation of Notch receptors by Lunatic Fringe (Lfng), which encodes an O-fucosylpeptide 3-β-N-acetylglucosaminyltransferase known to modify epidermal growth factor ..
  21. Moloney D, Panin V, Johnston S, Chen J, Shao L, Wilson R, et al. Fringe is a glycosyltransferase that modifies Notch. Nature. 2000;406:369-75 pubmed
  22. Zhang S, Chung W, Wu G, Egan S, Xu K. Tumor-suppressive activity of Lunatic Fringe in prostate through differential modulation of Notch receptor activation. Neoplasia. 2014;16:158-67 pubmed publisher
    ..Here, we report a critical role for Lunatic Fringe (Lfng), which encodes an O-fucosylpeptide 3-ß-N-acetylglucosaminyltransferase known to modify epidermal growth factor ..
  23. Xu K, Usary J, Kousis P, Prat A, Wang D, Adams J, et al. Lunatic fringe deficiency cooperates with the Met/Caveolin gene amplicon to induce basal-like breast cancer. Cancer Cell. 2012;21:626-41 pubmed publisher
    ..Here we show that deletion of Lfng, a sugar transferase that prevents Notch activation by Jagged ligands, enhances stem/progenitor cell proliferation...
  24. Del Castillo Velasco Herrera M, van der Weyden L, Nsengimana J, Speak A, Sjöberg M, Bishop D, et al. Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis. Mol Oncol. 2018;12:239-255 pubmed publisher
    ..By comparing expression data between species, we identified lunatic fringe (LFNG), among 28 genes whose expression level is predictive of poor prognosis and whose altered expression is associated ..
  25. Dunwoodie S. Mutation of the fucose-specific beta1,3 N-acetylglucosaminyltransferase LFNG results in abnormal formation of the spine. Biochim Biophys Acta. 2009;1792:100-11 pubmed publisher
    ..and vertebral column development in humans; of particular interest here is mutation of the LUNATIC FRINGE (LFNG) gene, which causes SCD type 3...
  26. Moran J, Johnston S, Rauskolb C, Bhalerao J, Bowcock A, Vogt T. Genomic structure, mapping, and expression analysis of the mammalian Lunatic, Manic, and Radical fringe genes. Mamm Genome. 1999;10:535-41 pubmed
    ..three members of the mammalian fringe gene family, Manic fringe (Mfng), Radical fringe (Rfng), and Lunatic fringe (Lfng), were identified on the basis of their similarity to Drosophila fringe (fng) and their participation in the ..
  27. Sparrow D, Chapman G, Wouters M, Whittock N, Ellard S, Fatkin D, et al. Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype. Am J Hum Genet. 2006;78:28-37 pubmed
    ..Here, we have used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD...
  28. Egan S, Herbrick J, Tsui L, Cohen B, Flock G, Beatty B, et al. Mapping of the human Lunatic Fringe (LFNG) gene to 7p22 and Manic Fringe (MFNG) to 22q12. Genomics. 1998;54:576-7 pubmed
  29. Cole S, Levorse J, Tilghman S, Vogt T. Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis. Dev Cell. 2002;3:75-84 pubmed
    Somitogenesis requires a segmentation clock and Notch signaling. Lunatic fringe (Lfng) expression in the presomitic mesoderm (PSM) cycles in the posterior PSM, is refined in the segmenting somite to the rostral compartment, and is ..
  30. Yu A, Zambrano R, Cristian I, Price S, Bernhard B, Zucker M, et al. Variable developmental delays and characteristic facial features-A novel 7p22.3p22.2 microdeletion syndrome?. Am J Med Genet A. 2017;173:1593-1600 pubmed publisher
    ..47?Mb region of overlap which contained 7 OMIM genes: EIP3B, CHST12, LFNG, BRAT1, TTYH3, AMZ1, and GNA12. We propose that monosomy of this region represents a novel microdeletion syndrome...
  31. Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H. Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation. J Biol Chem. 2001;276:25753-8 pubmed
    ..Although both manic fringe (mFng) and lunatic fringe (lFng) decreased the binding of Jagged1 to Notch2 and not that of Delta1, the decrease by mFng was greater in degree than ..
  32. Reedijk M, Odorcic S, Zhang H, Chetty R, Tennert C, Dickson B, et al. Activation of Notch signaling in human colon adenocarcinoma. Int J Oncol. 2008;33:1223-9 pubmed
    ..In a small cohort of tumors, JAGGED ligands, NOTCH1, LFNG and HES1 were expressed at levels similar to, or higher than, levels observed in the crypt...
  33. Shao L, Moloney D, Haltiwanger R. Fringe modifies O-fucose on mouse Notch1 at epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region. J Biol Chem. 2003;278:7775-82 pubmed
    ..These findings provide insight into potential mechanisms by which Fringe action on Notch receptors may influence both the affinity of Notch-ligand binding and cell-autonomous inhibition of Notch signaling by ligand. ..