View source for Neurofibromin 1

{{BioPsy}}
{{PBB|geneid=4763}}
'''Neurofibromin 1''' also known as '''neurofibromatosis-related protein NF-1''' is a [[protein]] that in humans is encoded by the ''NF1'' [[gene]].<ref name="pmid1715669">{{cite journal | author = Skuse GR, Kosciolek BA, Rowley PT | title = The neurofibroma in von Recklinghausen neurofibromatosis has a unicellular origin | journal = Am. J. Hum. Genet. | volume = 49 | issue = 3 | pages = 600–7 | year = 1991 | month = September | pmid = 1715669 | pmc = 1683134 | doi = | url = | issn = }}</ref> Mutations in the NF1 gene are associated with [[neurofibromatosis type I]] (also known as von Recklinghausen disease) and [[Watson syndrome]].<ref name="pmid10625171">{{cite journal | author = Rasmussen SA, Friedman JM | title = NF1 gene and neurofibromatosis 1 | journal = Am. J. Epidemiol. | volume = 151 | issue = 1 | pages = 33–40 | year = 2000 | month = January | pmid = 10625171 | doi = 10.1093/oxfordjournals.aje.a010118| url = | issn = }}</ref>

==  Function ==

NF1 encodes the protein neurofibromin, which appears to be a negative regulator of the [[Ras_subfamily#Function|ras signal transduction pathway]].

NF1 is found within the mammalian postsynapse, where it is known to bind to the [[NMDA receptor]] complex. It has been found to lead to deficits in learning, and it is suspected that this is a result of its regulation of the [[Ras pathway]]. It is known to regulate the [[GTPase]] [[HRAS]], causing the hydrolyzation of GTP and thereby inactivating it.<ref name="Trovó-Marqui AB, Tajara EH 2006 1–13">{{cite journal  | author=Trovó-Marqui AB, Tajara EH |title=Neurofibromin: a general outlook |journal=Clin. Genet. |volume=70 |issue= 1 |pages= 1–13 |year= 2006 |pmid= 16813595 |doi= 10.1111/j.1399-0004.2006.00639.x }}</ref> Within the [[synapse]] HRAS is known to activate [[Src (gene)|Src]], which itself phosphorylates [[GRIN2A]], leading to its inclusion in the synaptic membrane.

NF1 is also known to interact with [[CASK]] through [[syndecan]], a protein which is involved in the KIF17/ABPA1/CASK/LIN7A complex, which is involved in trafficking [[GRIN2B]] to the synapse. This suggests that NF1 has a role in the transportation of the NMDA receptor subunits to the synapse and its membrane. NF1 is also believed to be involved in the synaptic ATP-PKA-cAMP pathway, through modulation of [[adenylyl cyclase]]. It is also known to bind the [[caveolin 1]], a protein which regualtes p21ras, PKC and growth response factors.<ref name="Trovó-Marqui AB, Tajara EH 2006 1–13"/>

== Clinical significance ==

Mutations linked to neurofibromatosis type 1 led to the identification of the NF1 gene. The neurofibromin gene may be mutated in thousands of ways, resulting in many possible clinical outcomes.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/12403553 "NF1 mutations and molecular testing", by SA Thomson, L Fishbein and MR Wallace, J Child Neurol 2002 Aug; 17(8); 555-61; discussion 571-2, 646-51]</ref>  In addition to [[neurofibromatosis type I]], mutations in NF1 can also lead to [[juvenile myelomonocytic leukemia]], [[Watson syndrome]],<ref>{{cite web | title = Entrez Gene: NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4763| accessdate = }}</ref>  and [[breast cancer]].<ref name=nature11412>{{cite journal |last1=The Cancer Genome Atlas Network |first1= |last2= |first2= |year=2012 |title=Comprehensive molecular portraits of human breast tumours |journal=Nature |volume= 490|issue= 7418|pages= 61–70|publisher=Nature Publishing Group |doi=10.1038/nature11412 |url=http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11412.html |accessdate=24 September 2012 |pmid=23000897}}</ref> Types of mutations include frameshift, nonsense, missense, splicing alteration and deletion mutations, and loss of heterozygosity.<ref>{{cite journal | url = http://www.ncbi.nlm.nih.gov/pubmed/19142971 | pmid = 19142971 | doi=10.1002/path.2494 | volume=217 | issue=5 | title=Germline and somatic NF1 mutations in sporadic and NF1-associated malignant peripheral nerve sheath tumours | year=2009 | month=April | journal=J. Pathol. | pages=693–701 | author=Bottillo I | author-separator = , | author2 = Ahlquist T | author3 = Brekke H | display-authors = 3 | last4 = Danielsen | first4 = Stine A | last5 = Van Den Berg | first5 = Eva | last6 = Mertens | first6 = Fredrik | last7 = Lothe | first7 = Ragnhild A | last8 = Dallapiccola | first8 = Bruno}}</ref><ref>[http://herkules.oulu.fi/isbn9514266463/html/x208.html "Nf1 tumor suppressor in skin:: Expression in response to tissue trauma and in cellular differentiation"]</ref><ref>{{cite pmid|10677298|noedit}}</ref><ref>{{Cite doi|10.1016/j.pediatrneurol.2007.07.005|noedit}}</ref>

==RNA editing==
=== Type ===
The type of editing is a [[cytidine]] to [[uridine]] (C to U) site specific [[deamination]]. The editing site in NF1 [[messenger RNA|mRNA]] was determined to have a high homology to the [[Apolipoprotein B|ApoB]] editing site where double stranded mRNA undergoes editing by the ApoB holoenzyme.<ref name="pmid8602361"/> This alluded to the same [[Enzyme#Cofactors|holoenzyme]] involved in ApoB mRNA editing maybe involved in editing of NF1.<ref name="pmid7707816">{{cite journal | author = Skuse GR, Ludlow JW | title = Tumour suppressor genes in disease and therapy | journal = Lancet | volume = 345 | issue = 8954 | pages = 902–6 | year = 1995 | month = April | pmid = 7707816 | doi =10.1016/S0140-6736(95)90015-2  }}</ref> There are at least four different alternatively spliced forms of the protein, two of which are better defined. They differ by the inclusion of [[exon]] 23A. Recent experiments have shown that apobec-1 is indeed expressed outside the GI luminal tract in some tumors and the inclusion of downstream exon 23a is preferentially found in these edited transcripts. These two features  distinguishes them from tumors where RNA editing does not occur.<ref name="pmid11727199">{{cite journal | author = Mukhopadhyay D, Anant S, Lee RM, Kennedy S, Viskochil D, Davidson NO | title = 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 | journal = Am. J. Hum. Genet. | volume = 70 | issue = 1 | pages = 38–50 | year = 2002 | month = January | pmid = 11727199 | pmc = 384902 | doi = 10.1086/337952 }}</ref>

===Location ===
The cytidine in the [[arginine]] codon (CGA) is deaminated to a uracil creating an inframe translational stop codon. The editing site is located at nucleotide position 2914.A region (nucleotides 2909-2930) was found to have a high homology  to that found in the 21 nucleotide editing region  of  ApoB mRNA. It was suggested that the same editsome involved in ApoB mRNA editing may also be involved in NF1 mRNA editing. However the 6 nucleotide stretch from the edited cytidine and the start of the mooring sequence is two nucleotides longer than the ideal sequence required for ApoB mRNA editing. Also the region contains 2 guanidines which would be tolerated but again would not be ideal for ApoB mRNA editing. The mooring sequence and regulatory sequence are thought to be sufficient for editing to occur by ApoB mRNA editing machinery. This was determined by site mutagenesis experiments.<ref name="pmid1461733">{{cite journal | author = Backus JW, Smith HC | title = Three distinct RNA sequence elements are required for efficient apolipoprotein B (apoB) RNA editing in vitro | journal = Nucleic Acids Res. | volume = 20 | issue = 22 | pages = 6007–14 | year = 1992 | month = November | pmid = 1461733 | pmc = 334467 | doi = 10.1093/nar/20.22.6007  }}</ref>

==== Regulation ====
NF1 RNA editing is not regulated by limited amounts of APOBEC-1. This implies that different factors are involved in NF1 mRNA editing than those associated with ApoB RNA editing.  It is thought that different trans acting factors may be involved in the two editing processes.<ref name="pmid8602361"/> Also, the region surrounding the editing region in NF1 mRNA is GC rich instead of the preferred AT rich sequence found in ApoB mRNA editing site. This reason as well as the longer spacer element of NF1 mRNA than that of ApoB mRNA are thought to be factors in the difference in frequency of editing of the two mRNAs (20% NF1, 90% ApoB).<ref name="pmid8051066">{{cite journal | author = Driscoll DM, Zhang Q | title = Expression and characterization of p27, the catalytic subunit of the apolipoprotein B mRNA editing enzyme | journal = J. Biol. Chem. | volume = 269 | issue = 31 | pages = 19843–7 | year = 1994 | month = August | pmid = 8051066 | doi = }}</ref> Editing occurs in a higher frequency in tumours compared to the relative normal tissues.<ref name="pmid8602361"/> There is a higher frequency of edting in the NF1 mRNA which includes Exon 23A in tumors.<ref name="pmid11727199" />

==== Conservation ====
The editing site is thought not to be conserved as editing of NF1 mRNA does not occur in the rat or mouse but these species do express several alternatively spliced mRNAs.<ref name="pmid8602361">{{cite journal | author = Skuse GR, Cappione AJ, Sowden M, Metheny LJ, Smith HC | title = The neurofibromatosis type I messenger RNA undergoes base-modification RNA editing | journal = Nucleic Acids Res. | volume = 24 | issue = 3 | pages = 478–85 | year = 1996 | month = February | pmid = 8602361 | pmc = 145654 | doi = 10.1093/nar/24.3.478 }}</ref><ref name="pmid9300663">{{cite journal | author = Skuse GR, Cappione AJ | title = RNA processing and clinical variability in neurofibromatosis type I (NF1) | journal = Hum. Mol. Genet. | volume = 6 | issue = 10 | pages = 1707–12 | year = 1997 | pmid = 9300663 | doi = 10.1093/hmg/6.10.1707 }}</ref> One of these alternatively spliced isoforms known as TYPE III in rats and mice introduces a frameshift that introduces a stop codon by inclusion of a 41 base pair exon.<ref name="pmid9012403">{{cite journal | author = Cappione AJ, French BL, Skuse GR | title = A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors | journal = Am. J. Hum. Genet. | volume = 60 | issue = 2 | pages = 305–12 | year = 1997 | month = February | pmid = 9012403 | pmc = 1712412 | doi = }}</ref>

===Consequences===
====Structure====
Editing results in a codon change from an arginine codon (CGA) to an in frame stop codon (UGA) due to a base change at nucleotide 2914. The introduction of an inframe stop codon results in a translated protein that is truncated. The translated protein is thought to be lacking its GAP Related Domain (GRD)  that shares a  homology to mammalian GTPase activating (GAP) domain and yeast inhibitor of [[Ras subfamily|RAS protein]] 1 and 2 domains.<ref name="pmid8602361"/>

====Function====
The gene product is neurofibromin, a tumor-suppressor, a region of which functions as a GTPase-activating protein shown to be involved in negative regulation of the [[anti-apoptotic Ras signalling cascade|RAS pathway]].<ref name="pmid9012403"/><ref name="pmid11239415">{{cite journal | author = Cichowski K, Jacks T | title = NF1 tumor suppressor gene function: narrowing the GAP | journal = Cell | volume = 104 | issue = 4 | pages = 593–604 | year = 2001 | month = February | pmid = 11239415 | doi = 10.1016/S0092-8674(01)00245-8 }}</ref> NF1 mRNA editing has been detected in a wide range of tissues. Editing results in a truncated protein being translated that does not contain this region. The GTPase region has a high homology to with mammalian and yeast (GAPs) which would suggest that neurofibromin plays a role in negative regulation of RAS signal transduction pathways. It is thought that editing therefore would result in the loss of the proteins tumour suppressor activity.<ref name="pmid7926784">{{cite journal | author = Brannan CI, Perkins AS, Vogel KS, Ratner N, Nordlund ML, Reid SW, Buchberg AM, Jenkins NA, Parada LF, Copeland NG | title = Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues | journal = Genes Dev. | volume = 8 | issue = 9 | pages = 1019–29 | year = 1994 | month = May | pmid = 7926784 | doi = 10.1101/gad.8.9.1019 }}</ref><ref name="pmid2121371">{{cite journal | author = Ballester R, Marchuk D, Boguski M, Saulino A, Letcher R, Wigler M, Collins F | title = The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins | journal = Cell | volume = 63 | issue = 4 | pages = 851–9 | year = 1990 | month = November | pmid = 2121371 | doi =10.1016/0092-8674(90)90151-4 }}</ref><ref name="pmid2116237">{{cite journal | author = Xu GF, O'Connell P, Viskochil D, Cawthon R, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R | title = The neurofibromatosis type 1 gene encodes a protein related to GAP | journal = Cell | volume = 62 | issue = 3 | pages = 599–608 | year = 1990 | month = August | pmid = 2116237 | doi =10.1016/0092-8674(90)90024-9  }}</ref> This corresponds to the observed increase in editing in tumors compared to normal tissue, however further research into the role of mRNA editing of NF1 mRNA in pathogenesis in tumours needs to be undertaked.<ref name="pmid8602361"/><ref name="pmid9300663"/> There is a correlation in an increase of editing in some tumors and the degree of malignancy of the tumor suggesting a relationship between the two.<ref name="pmid9012403"/> Recently further evidence of the role of editing in pathogenesis in tumors.It was observed that C to U editing of NF1 mRNA occurs in a fraction of tumor samples of NF1 patients  where APOBEC-1 is also expressed. This was an important find as was the first time APOBEC-1 expression was proven experimentally outside the luminal cells of the tract.<ref name="pmid11727199" /> The [[N-terminus]] of the protein has a region demonstrated to be able to bind [[microtubule]]s. It has been suggested that since the edited protein still retains this region, that a function of this editing is to displace microtubules from the full length neurofiromin protein. This would liberate the full length protein to interact with RAS.<ref name="pmid9300663"/><ref name="pmid8332934">{{cite journal | author = Gregory PE, Gutmann DH, Mitchell A, Park S, Boguski M, Jacks T, Wood DL, Jove R, Collins FS | title = Neurofibromatosis type 1 gene product (neurofibromin) associates with microtubules | journal = Somat. Cell Mol. Genet. | volume = 19 | issue = 3 | pages = 265–74 | year = 1993 | month = May | pmid = 8332934 | doi =10.1007/BF01233074  }}</ref>

=====Neurofibromitosis=====
It is thought that RNA editing may account for the wide variation in phenotype of this condition even among siblings.<ref name="pmid2511318">{{cite journal | author = Huson SM, Compston DA, Clark P, Harper PS | title = A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity | journal = J. Med. Genet. | volume = 26 | issue = 11 | pages = 704–11 | year = 1989 | month = November | pmid = 2511318 | pmc = 1015740 | doi =10.1136/jmg.26.11.704 }}</ref> Also 50% of new cases have new mutations. The frequency is too high to explain these cases as spontaneous mutations therefore RNA editing of NF1 rna may provide an alternative reason for the variation of phenotype.<ref name="pmid7707816"/>

==Model organisms==
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Nf1'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
|-
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#C40000"|Abnormal<ref name="Dysmorphology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAHR/dysmorphology/ |title=Dysmorphology data for Nf1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#C40000"|Abnormal<ref name="Peripheral blood lymphocytes">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAHR/peripheral-blood-lymphocytes/ |title=Peripheral blood lymphocytes data for Nf1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Skin Histopathology || bgcolor="#488ED3"|Normal
|-
| Brain histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAHR/salmonella-challenge/ |title=''Salmonella'' infection data for Nf1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAHR/citrobacter-challenge/ |title=''Citrobacter'' infection data for Nf1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal| doi = 10.1111/j.1755-3768.2010.4142.x| title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice| year = 2010| author = Gerdin AK| journal = Acta Ophthalmologica| volume = 88| issue = S248| pages = 0 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of NF1 function. A conditional [[knockout mouse]] line, called ''Nf1<sup>tm1a(KOMP)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Nf1 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4364806 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="pmid21677750">{{Cite pmid|21677750|noedit}}</ref><ref name="mouse_library">{{cite journal |author=Dolgin E |title=Mouse library set to be knockout |journal=Nature |volume=474 |issue=7351 |pages=262–3 |year=2011 |month=June |pmid=21677718 |doi=10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal |author=Collins FS, Rossant J, Wurst W |title=A mouse for all reasons |journal=Cell |volume=128 |issue=1 |pages=9–13 |year=2007 |month=January |pmid=17218247 |doi=10.1016/j.cell.2006.12.018 }}</ref>

Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal| author=van der Weyden L, White JK, Adams DJ, Logan DW| title=The mouse genetics toolkit: revealing function and mechanism | journal=Genome Biol | year= 2011 | volume= 12 | issue= 6 | pages= 224 | pmid=21722353 | doi=10.1186/gb-2011-12-6-224 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21722353| pmc=3218837  }}</ref> Twenty six tests were carried out on [[mutant]] mice and four significant abnormalities were observed.<ref name="mgp_reference" /> Over half the [[homozygous]] [[mutant]] embryos identified during gestation were dead, and in a separate study none survived until [[weaning]]. The remaining tests were carried out on [[heterozygous]] mutant adult mice: females displayed abnormal hair cycling while males had an decreased [[B cell]] number and an increased [[monocyte]] cell number.<ref name="mgp_reference" />

==Patent==

The neurofibromatosis gene was [[Gene patent|patented]] by the [[University of Michigan]], with the initial filing in 1991 and the patent granted in 2001.<ref>[http://www.freepatentsonline.com/6238861.pdf United States Patent US006238861B1]</ref>

==See also==

* [[SPRED1 gene]]

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
*{{cite journal  | author=Upadhyaya M, Shaw DJ, Harper PS |title=Molecular basis of neurofibromatosis type 1 (NF1): mutation analysis and polymorphisms in the NF1 gene |journal=Hum. Mutat. |volume=4 |issue= 2 |pages= 83–101 |year= 1994 |pmid= 7981724 |doi= 10.1002/humu.1380040202 }}
*{{cite journal  | author=Shen MH, Harper PS, Upadhyaya M |title=Molecular genetics of neurofibromatosis type 1 (NF1) |journal=J. Med. Genet. |volume=33 |issue= 1 |pages= 2–17 |year= 1996 |pmid= 8825042 |doi=10.1136/jmg.33.1.2  | pmc=1051805  }}
*{{cite journal  | author=Feldkamp MM, Gutmann DH, Guha A |title=Neurofibromatosis type 1: piecing the puzzle together |journal=The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques |volume=25 |issue= 3 |pages= 181–91 |year= 1998 |pmid= 9706718 |doi=  }}
*{{cite journal  | author=Hamilton SJ, Friedman JM |title=Insights into the pathogenesis of neurofibromatosis 1 vasculopathy |journal=Clin. Genet. |volume=58 |issue= 5 |pages= 341–4 |year= 2001 |pmid= 11140831 |doi=10.1034/j.1399-0004.2000.580501.x  }}
*{{cite journal  | author=Baralle D, Baralle M |title=Splicing in action: assessing disease causing sequence changes |journal=J. Med. Genet. |volume=42 |issue= 10 |pages= 737–48 |year= 2006 |pmid= 16199547 |doi= 10.1136/jmg.2004.029538  | pmc=1735933 }}
*{{cite journal  | author=Mensink KA |title=Connective tissue dysplasia in five new patients with NF1 microdeletions: further expansion of phenotype and review of the literature |journal=J. Med. Genet. |volume=43 |issue= 2 |pages= e8 |year= 2006 |pmid= 16467218 |doi= 10.1136/jmg.2005.034256  | pmc=2603036  | author-separator=,  | author2=Ketterling RP  | author3=Flynn HC  | display-authors=3  | last4=Knudson  | first4=RA  | last5=Lindor  | first5=NM  | last6=Heese  | first6=BA  | last7=Spinner  | first7=RJ  | last8=Babovic-Vuksanovic  | first8=D }}
*{{cite journal  | author=Trovó-Marqui AB, Tajara EH |title=Neurofibromin: a general outlook |journal=Clin. Genet. |volume=70 |issue= 1 |pages= 1–13 |year= 2006 |pmid= 16813595 |doi= 10.1111/j.1399-0004.2006.00639.x }}
{{refend}}

==External links==
* [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=nf1  GeneReviews/NCBI/NIH/UW entry on Neurofibromatosis 1]
* [http://genome.ucsc.edu/cgi-bin/hgGene?hgg_gene=uc002hgf.1&org=human Human Gene NF1 (uc002hgf.1)]
* [http://www.genecards.org/cgi-bin/carddisp.pl?gene=NF1 neurofibromin 1] from [[GeneCards]]
* [http://darned.ucc.ie Database of RNA editing]

{{PDB Gallery|geneid=4763}}
{{GTP-binding protein regulators}}
{{Tumor suppressor genes}}
{{Use dmy dates|date=January 2012}}

[[Category:Genes mutated in mice]]
[[Category:Proteins]]
[[CAtegory:Synapse]]
{{enWP|Neurofibromin 1}}