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Gene Review

NF1  -  neurofibromin 1

Homo sapiens

Synonyms: NFNS, Neurofibromatosis-related protein NF-1, Neurofibromin, VRNF, WSS
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Disease relevance of NF1


Psychiatry related information on NF1


High impact information on NF1


Chemical compound and disease context of NF1


Biological context of NF1

  • Numerous point mutations found in NF1 patients or derived from genetic screening protocols can be analysed on the basis of the three-dimensional structural model, which also allows identification of the site where structural changes in a differentially spliced isoform are to be expected [19].
  • Missense mutations found in NF1 patients map to NF1GRD, underscoring its importance for pathogenesis [19].
  • To elucidate the extent of microheterogeneity at the deletion boundaries, we used single-copy DNA fragments from the extreme ends of the deleted segment to perform FISH on metaphase chromosomes from eight patients with NF1 who had large deletions [20].
  • The analysis of neurofibromin transcripts from different neurofibromatosis type 1 (NF1) patients revealed the skipping of exons containing PTCs [21].
  • Finally, adenovirus-mediated transfection of HepG2 cells revealed induction of editing of apoB RNA, along with preferential editing of NF1 transcripts containing exon 23A [14].

Anatomical context of NF1


Associations of NF1 with chemical compounds


Physical interactions of NF1


Enzymatic interactions of NF1


Regulatory relationships of NF1

  • In addition, the exogenous expression of the NF1-GTPase-activating protein-related domain suppressed the NF1 siRNA-induced phenotypes [24].
  • There may be a neurofibromin-induced and p21ras-mediated differentiation pathway of neuronal stem cells that is blocked in PNET [36].
  • The GTPase of wild-type ras p21 was stimulated by NF1 GRD, but oncogenic mutants of ras p21 (Asp-12 and Val-12) were unaffected, and the GTPase of an effector mutant (Ala-38) was only weakly stimulated [1].
  • CONCLUSIONS: These results depict an early fetal period when the NF1 tumor suppressor is abundantly expressed in epidermis and associated with cytokeratin filaments [37].
  • We now describe a sequence upstream of and partially overlapping the NF1 site that activates the MBP promoter in oligodendrocytes, but not in Cos-7 cells [38].

Other interactions of NF1

  • When expressed in non-mammalian systems, the region of the NF1 gene homologous to p120GAP produces a protein with GAP-like activity [3].
  • We mapped the MenX locus to the distal part of rat chromosome 4, excluding the homologs of the genes responsible for the MEN syndromes (RET and MEN1) and syndromes with an endocrine tumor component (VHL and NF1) [39].
  • Taken together, the data support the hypothesis that C-->U RNA editing of the NF1 transcript occurs both in a subset of PNSTs and in an alternatively spliced form containing a downstream exon, presumably an optimal configuration for enzymatic deamination by apobec-1 [14].
  • Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras [22].
  • These results point to kinesin-1 as a common denominator between NF1 and NF2 [17].

Analytical, diagnostic and therapeutic context of NF1


  1. The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Martin, G.A., Viskochil, D., Bollag, G., McCabe, P.C., Crosier, W.J., Haubruck, H., Conroy, L., Clark, R., O'Connell, P., Cawthon, R.M. Cell (1990) [Pubmed]
  2. Somatic mutations in the neurofibromatosis 1 gene in human tumors. Li, Y., Bollag, G., Clark, R., Stevens, J., Conroy, L., Fults, D., Ward, K., Friedman, E., Samowitz, W., Robertson, M. Cell (1992) [Pubmed]
  3. Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Basu, T.N., Gutmann, D.H., Fletcher, J.A., Glover, T.W., Collins, F.S., Downward, J. Nature (1992) [Pubmed]
  4. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Astuti, D., Latif, F., Dallol, A., Dahia, P.L., Douglas, F., George, E., Sköldberg, F., Husebye, E.S., Eng, C., Maher, E.R. Am. J. Hum. Genet. (2001) [Pubmed]
  5. Selective disactivation of neurofibromin GAP activity in neurofibromatosis type 1. Klose, A., Ahmadian, M.R., Schuelke, M., Scheffzek, K., Hoffmeyer, S., Gewies, A., Schmitz, F., Kaufmann, D., Peters, H., Wittinghofer, A., Nürnberg, P. Hum. Mol. Genet. (1998) [Pubmed]
  6. Tuberous sclerosis complex and neurofibromatosis type 1: the two most common neurocutaneous diseases. Kandt, R.S. Neurologic clinics. (2003) [Pubmed]
  7. A common set of at least 11 functional genes is lost in the majority of NF1 patients with gross deletions. Jenne, D.E., Tinschert, S., Stegmann, E., Reimann, H., Nürnberg, P., Horn, D., Naumann, I., Buske, A., Thiel, G. Genomics (2000) [Pubmed]
  8. Serotonin transporter gene polymorphism and psychiatric disorders in NF1 patients. Bellivier, F., Laplanche, J.L., Fournier, G., Wolkenstein, P. Am. J. Med. Genet. (2001) [Pubmed]
  9. Treatment of ADHD in neurofibromatosis type 1. Mautner, V.F., Kluwe, L., Thakker, S.D., Leark, R.A. Developmental medicine and child neurology. (2002) [Pubmed]
  10. Psychological disturbance and sleep disorders in children with neurofibromatosis type 1. Johnson, H., Wiggs, L., Stores, G., Huson, S.M. Developmental medicine and child neurology. (2005) [Pubmed]
  11. Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion. Raedt, T.D., Stephens, M., Heyns, I., Brems, H., Thijs, D., Messiaen, L., Stephens, K., Lazaro, C., Wimmer, K., Kehrer-Sawatzki, H., Vidaud, D., Kluwe, L., Marynen, P., Legius, E. Nat. Genet. (2006) [Pubmed]
  12. Mitotic recombination effects homozygosity for NF1 germline mutations in neurofibromas. Serra, E., Rosenbaum, T., Nadal, M., Winner, U., Ars, E., Estivill, X., Lázaro, C. Nat. Genet. (2001) [Pubmed]
  13. NF1 tumor suppressor gene function: narrowing the GAP. Cichowski, K., Jacks, T. Cell (2001) [Pubmed]
  14. C-->U editing of neurofibromatosis 1 mRNA occurs in tumors that express both the type II transcript and apobec-1, the catalytic subunit of the apolipoprotein B mRNA-editing enzyme. Mukhopadhyay, D., Anant, S., Lee, R.M., Kennedy, S., Viskochil, D., Davidson, N.O. Am. J. Hum. Genet. (2002) [Pubmed]
  15. Signal therapy of human pancreatic cancer and NF1-deficient breast cancer xenograft in mice by a combination of PP1 and GL-2003, anti-PAK1 drugs (Tyr-kinase inhibitors). Hirokawa, Y., Levitzki, A., Lessene, G., Baell, J., Xiao, Y., Zhu, H., Maruta, H. Cancer Lett. (2007) [Pubmed]
  16. Pheochromocytoma in von Hippel-Lindau disease and neurofibromatosis type 1. Opocher, G., Conton, P., Schiavi, F., Macino, B., Mantero, F. Fam. Cancer (2005) [Pubmed]
  17. The motor protein kinesin-1 links neurofibromin and merlin in a common cellular pathway of neurofibromatosis. Hakimi, M.A., Speicher, D.W., Shiekhattar, R. J. Biol. Chem. (2002) [Pubmed]
  18. Neurofibromin-deficient Schwann cells have increased lysophosphatidic acid dependent survival and migration-implications for increased neurofibroma formation during pregnancy. Nebesio, T.D., Ming, W., Chen, S., Clegg, T., Yuan, J., Yang, Y., Estwick, S.A., Li, Y., Li, X., Hingtgen, C.M., Yang, F.C. Glia (2007) [Pubmed]
  19. Structural analysis of the GAP-related domain from neurofibromin and its implications. Scheffzek, K., Ahmadian, M.R., Wiesmüller, L., Kabsch, W., Stege, P., Schmitz, F., Wittinghofer, A. EMBO J. (1998) [Pubmed]
  20. Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions. Jenne, D.E., Tinschert, S., Reimann, H., Lasinger, W., Thiel, G., Hameister, H., Kehrer-Sawatzki, H. Am. J. Hum. Genet. (2001) [Pubmed]
  21. Nearby stop codons in exons of the neurofibromatosis type 1 gene are disparate splice effectors. Hoffmeyer, S., Nürnberg, P., Ritter, H., Fahsold, R., Leistner, W., Kaufmann, D., Krone, W. Am. J. Hum. Genet. (1998) [Pubmed]
  22. Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras. Kalra, R., Paderanga, D.C., Olson, K., Shannon, K.M. Blood (1994) [Pubmed]
  23. RNA processing and clinical variability in neurofibromatosis type I (NF1). Skuse, G.R., Cappione, A.J. Hum. Mol. Genet. (1997) [Pubmed]
  24. The neurofibromatosis type 1 gene product neurofibromin enhances cell motility by regulating actin filament dynamics via the Rho-ROCK-LIMK2-cofilin pathway. Ozawa, T., Araki, N., Yunoue, S., Tokuo, H., Feng, L., Patrakitkomjorn, S., Hara, T., Ichikawa, Y., Matsumoto, K., Fujii, K., Saya, H. J. Biol. Chem. (2005) [Pubmed]
  25. The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann cells and is a mitogen for neurofibroma-derived cells. Mashour, G.A., Ratner, N., Khan, G.A., Wang, H.L., Martuza, R.L., Kurtz, A. Oncogene (2001) [Pubmed]
  26. Genomic characterization of the Neurofibromatosis Type 1 gene of Fugu rubripes. Kehrer-Sawatzki, H., Maier, C., Moschgath, E., Elgar, G., Krone, W. Gene (1998) [Pubmed]
  27. The importance of two conserved arginine residues for catalysis by the ras GTPase-activating protein, neurofibromin. Sermon, B.A., Lowe, P.N., Strom, M., Eccleston, J.F. J. Biol. Chem. (1998) [Pubmed]
  28. Phosphorylation of neurofibromin by PKC is a possible molecular switch in EGF receptor signaling in neural cells. Mangoura, D., Sun, Y., Li, C., Singh, D., Gutmann, D.H., Flores, A., Ahmed, M., Vallianatos, G. Oncogene (2006) [Pubmed]
  29. NF1 inactivation in adult acute myelogenous leukemia. Parkin, B., Ouillette, P., Wang, Y., Liu, Y., Wright, W., Roulston, D., Purkayastha, A., Dressel, A., Karp, J., Bockenstedt, P., Al-Zoubi, A., Talpaz, M., Kujawski, L., Liu, Y., Shedden, K., Shakhan, S., Li, C., Erba, H., Malek, S.N. Clin. Cancer Res. (2010) [Pubmed]
  30. Parallels between tuberous sclerosis complex and neurofibromatosis 1: common threads in the same tapestry. Gutmann, D.H. Seminars in pediatric neurology. (1998) [Pubmed]
  31. Bipartite interaction between neurofibromatosis type I protein (neurofibromin) and syndecan transmembrane heparan sulfate proteoglycans. Hsueh, Y.P., Roberts, A.M., Volta, M., Sheng, M., Roberts, R.G. J. Neurosci. (2001) [Pubmed]
  32. Transcription of the promoter of the rat NF-1 gene depends on the integrity of an Sp1 recognition site. Ammendola, R., Gounari, F., Piaggio, G., De Simone, V., Cortese, R. Mol. Cell. Biol. (1990) [Pubmed]
  33. Transcription of the rat p53 gene is mediated by factor binding to two recognition motifs of NF1-like protein. Lee, M., Song, H., Park, S., Park, J. Biol. Chem. (1998) [Pubmed]
  34. Repression of the human adenine nucleotide translocase-2 gene in growth-arrested human diploid cells: the role of nuclear factor-1. Luciakova, K., Barath, P., Poliakova, D., Persson, A., Nelson, B.D. J. Biol. Chem. (2003) [Pubmed]
  35. Schwann cell lines derived from malignant peripheral nerve sheath tumors respond abnormally to platelet-derived growth factor-BB. Dang, I., DeVries, G.H. J. Neurosci. Res. (2005) [Pubmed]
  36. Analysis of the GAP-related domain of the neurofibromatosis type 1 (NF1) gene in childhood brain tumors. Scheurlen, W.G., Senf, L. Int. J. Cancer (1995) [Pubmed]
  37. Functional expression of NF1 tumor suppressor protein: association with keratin intermediate filaments during the early development of human epidermis. Malminen, M., Peltonen, S., Koivunen, J., Peltonen, J. BMC Dermatol. (2002) [Pubmed]
  38. MEBA derepresses the proximal myelin basic protein promoter in oligodendrocytes. Taveggia, C., Pizzagalli, A., Feltri, M.L., Grinspan, J.B., Kamholz, J., Wrabetz, L. J. Biol. Chem. (1998) [Pubmed]
  39. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Pellegata, N.S., Quintanilla-Martinez, L., Siggelkow, H., Samson, E., Bink, K., H??fler, H., Fend, F., Graw, J., Atkinson, M.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  40. Human breast cancer MDA-MB-231 cells fail to express the neurofibromin protein, lack its type I mRNA isoform and show accumulation of P-MAPK and activated Ras. Ogata, H., Sato, H., Takatsuka, J., De Luca, L.M. Cancer Lett. (2001) [Pubmed]
  41. Expression of neurofibromin, the neurofibromatosis 1 gene product: studies in human neuroblastoma cells and rat brain. Huynh, D.P., Lin, C.T., Pulst, S.M. Neurosci. Lett. (1992) [Pubmed]
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