Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Neurofibromin

The NF1 gene ecodes a protein involved in signal transduction. It is a negative regulator of the intracellular ras pathway. Mutations cause autosomal dominant disorder such as neurofibromatosis type 1, Watson syndrome, and juvenile myelomonocytic leukemia. The latter is also seen with somatic mutations.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Research Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Juvenile myelomonocytic leukemia
NF1
Familial spinal neurofibromatosis
NF1
Neurofibromatosis 1
NF1
Neurofibromatosis-Noonan syndrome
NF1
Watson syndrome
NF1

References:

1.

Mukhopadhyay D et al. (2002) 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.

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2.

Wallace MR et al. (1991) A de novo Alu insertion results in neurofibromatosis type 1.

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3.

None (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways.

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4.

Allanson JE et al. (1985) Noonan phenotype associated with neurofibromatosis.

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5.

Colley A et al. (1996) Neurofibromatosis/Noonan phenotype: a variable feature of type 1 neurofibromatosis.

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6.

Baralle D et al. (2003) Different mutations in the NF1 gene are associated with Neurofibromatosis-Noonan syndrome (NFNS).

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7.

Bertola DR et al. (2005) Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both disorders in a patient.

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8.

De Luca A et al. (2005) NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome.

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9.

Stevenson DA et al. (2006) Clinical and molecular aspects of an informative family with neurofibromatosis type 1 and Noonan phenotype.

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10.

Thiel C et al. (2009) Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome.

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11.

Nyström AM et al. (2009) Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1.

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12.

Gutmann DH et al. (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2.

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13.

Heim RA et al. (1994) Screening for truncated NF1 proteins.

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14.

Upadhyaya M et al. (1997) Mutational and functional analysis of the neurofibromatosis type 1 (NF1) gene.

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15.

Silva AJ et al. (1997) A mouse model for the learning and memory deficits associated with neurofibromatosis type I.

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16.

Side L et al. (1997) Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders.

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17.

Skuse GR et al. (1997) RNA processing and clinical variability in neurofibromatosis type I (NF1).

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18.

Klose A et al. (1998) Selective disactivation of neurofibromin GAP activity in neurofibromatosis type 1.

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19.

Kluwe L et al. (1999) Allelic loss of the NF1 gene in NF1-associated plexiform neurofibromas.

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20.

Eisenbarth I et al. (2000) Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1.

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21.

Gutzmer R et al. (2000) Allelic loss at the neurofibromatosis type 1 (NF1) gene locus is frequent in desmoplastic neurotropic melanoma.

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22.

Gervasini C et al. (2002) Tandem duplication of the NF1 gene detected by high-resolution FISH in the 17q11.2 region.

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23.

Upadhyaya M et al. (2003) Three different pathological lesions in the NF1 gene originating de novo in a family with neurofibromatosis type 1.

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24.

Kluwe L et al. (2003) NF1 mutations and clinical spectrum in patients with spinal neurofibromas.

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25.

Wiest V et al. (2003) Somatic NF1 mutation spectra in a family with neurofibromatosis type 1: toward a theory of genetic modifiers.

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26.

Ferner RE et al. (2004) Neurofibromatous neuropathy in neurofibromatosis 1 (NF1).

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27.

Ragge NK et al. (2005) Heterozygous mutations of OTX2 cause severe ocular malformations.

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28.

Kolanczyk M et al. (2007) Multiple roles for neurofibromin in skeletal development and growth.

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29.

Henderson RA et al. (2007) Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia.

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30.

Pulst SM et al. (1991) Familial spinal neurofibromatosis: clinical and DNA linkage analysis.

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31.

Poyhonen M et al. (1997) Hereditary spinal neurofibromatosis: a rare form of NF1?

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32.

Ars E et al. (1998) A clinical variant of neurofibromatosis type 1: familial spinal neurofibromatosis with a frameshift mutation in the NF1 gene.

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33.

Kaufmann D et al. (2001) Spinal neurofibromatosis without café-au-lait macules in two families with null mutations of the NF1 gene.

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34.

Messiaen L et al. (2003) Independent NF1 mutations in two large families with spinal neurofibromatosis.

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35.

Upadhyaya M et al. (1992) Analysis of mutations at the neurofibromatosis 1 (NF1) locus.

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36.

Viskochil D et al. (1990) Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus.

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37.

Upadhyaya M et al. (1990) A 90 kb DNA deletion associated with neurofibromatosis type 1.

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38.

Wallace MR et al. (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients.

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39.

Huson SM et al. (1989) A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity.

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40.

Barker D et al. (1987) Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17.

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41.

Allanson JE et al. (1991) Watson syndrome: is it a subtype of type 1 neurofibromatosis?

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42.

Tassabehji M et al. (1993) Tandem duplication within a neurofibromatosis type 1 (NF1) gene exon in a family with features of Watson syndrome and Noonan syndrome.

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43.

Weiming X et al. (1992) Molecular analysis of neurofibromatosis type 1 mutations.

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44.

Stark M et al. (1992) Analysis of segregation and expression of an identified mutation at the neurofibromatosis type 1 locus.

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45.

Legius E et al. (1992) NF1-related locus on chromosome 15.

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46.

Daston MM et al. (1992) The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes.

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47.

DeClue JE et al. (1992) Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis.

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48.

Li Y et al. (1992) Somatic mutations in the neurofibromatosis 1 gene in human tumors.

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49.

Basu TN et al. (1992) Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients.

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50.

Xu G et al. (1992) Characterization of human adenylate kinase 3 (AK3) cDNA and mapping of the AK3 pseudogene to an intron of the NF1 gene.

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51.

Estivill X et al. (1991) Recurrence of a nonsense mutation in the NF1 gene causing classical neurofibromatosis type 1.

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52.

Marchuk DA et al. (1991) cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product.

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53.

Stark M et al. (1991) A small deletion and an adjacent base exchange in a potential stem-loop region of the neurofibromatosis 1 gene.

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54.

Gutmann DH et al. (1991) Identification of the neurofibromatosis type 1 gene product.

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55.

DeClue JE et al. (1991) Identification and characterization of the neurofibromatosis type 1 protein product.

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56.

Xu GF et al. (1990) The neurofibromatosis type 1 gene encodes a protein related to GAP.

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57.

Buchberg AM et al. (1990) Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway.

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58.

Hull J et al. (1994) The stop mutation R553X in the CFTR gene results in exon skipping.

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59.

Purandare SM et al. (1995) Characterisation of a novel splice donor mutation affecting position +1 in intron 18 of the NF-1 gene.

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60.

Lázaro C et al. (1995) Two further cases of mutation R1947X in the NF1 gene: screening for a relatively common recurrent mutation.

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61.

Vogel KS et al. (1995) Loss of neurofibromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons.

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62.

Li Y et al. (1995) Genomic organization of the neurofibromatosis 1 gene (NF1).

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63.

Horiuchi T et al. (1994) Nonsense mutations at Arg-1947 in two cases of familial neurofibromatosis type 1 in Japanese.

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64.

Valero MC et al. (1994) Characterization of four mutations in the neurofibromatosis type 1 gene by denaturing gradient gel electrophoresis (DGGE).

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65.

Nakafuku M et al. (1993) Suppression of oncogenic Ras by mutant neurofibromatosis type 1 genes with single amino acid substitutions.

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66.

Ainsworth PJ et al. (1993) Identification and characterization of sporadic and inherited mutations in exon 31 of the neurofibromatosis (NF1) gene.

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67.

Dietz HC et al. (1993) The skipping of constitutive exons in vivo induced by nonsense mutations.

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68.

Johnson MR et al. (1993) Inactivation of the NF1 gene in human melanoma and neuroblastoma cell lines without impaired regulation of GTP.Ras.

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69.

Skuse GR et al. (1996) The neurofibromatosis type I messenger RNA undergoes base-modification RNA editing.

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70.

Robinson PN et al. (1996) Recurrent 2-bp deletion in exon 10c of the NF1 gene in two cases of von Recklinghausen neurofibromatosis.

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71.

Wu R et al. (1996) Neurofibromatosis type I gene mutation in a patient with features of LEOPARD syndrome.

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72.

Cappione AJ et al. (1997) A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors.

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73.

The I et al. (1997) Rescue of a Drosophila NF1 mutant phenotype by protein kinase A.

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74.

Guo HF et al. (1997) Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides.

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75.

Maynard J et al. (1997) Characterization and significance of nine novel mutations in exon 16 of the neurofibromatosis type 1 (NF1) gene.

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76.

Abernathy CR et al. (1997) NF1 mutation analysis using a combined heteroduplex/SSCP approach.

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77.

Hoffmeyer S et al. (1998) Nearby stop codons in exons of the neurofibromatosis type 1 gene are disparate splice effectors.

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78.

Side LE et al. (1998) Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1.

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79.

Osborn MJ et al. (1999) Evaluation of the protein truncation test and mutation detection in the NF1 gene: mutational analysis of 15 known and 40 unknown mutations.

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80.

Faravelli F et al. (1999) Unusual clustering of brain tumours in a family with NF1 and variable expression of cutaneous features.

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81.

Ars E et al. (2000) Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1.

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82.

Fahsold R et al. (2000) Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain.

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83.

Park KC et al. (2000) A nonsense mutation at Arg-1947 in the NF1 gene in a case of neurofibromatosis type 1 in a Korean patient.

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84.

Messiaen LM et al. (2000) Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects.

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85.

Liu HX et al. (2001) A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes.

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86.

None (2001) The neurofibromatoses: when less is more.

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87.

Messiaen LM et al. () Exon 10b of the NF1 gene represents a mutational hotspot and harbors a recurrent missense mutation Y489C associated with aberrant splicing.

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88.

Luijten M et al. (2001) Duplication and transposition of the NF1 pseudogene regions on chromosomes 2, 14, and 22.

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89.

Weeber EJ et al. (2002) Molecular neurobiology of human cognition.

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90.

Cartegni L et al. (2002) Listening to silence and understanding nonsense: exonic mutations that affect splicing.

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91.

Fairbrother WG et al. (2002) Predictive identification of exonic splicing enhancers in human genes.

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92.

Kehrer-Sawatzki H et al. (2002) Molecular characterisation of t(17;22)(q11.2;q11.2) is not consistent with NF1 gene duplication.

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93.

Maris JM et al. (2002) Evidence for a hereditary neuroblastoma predisposition locus at chromosome 16p12-13.

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94.

Ruiz-Lozano P et al. (2003) Cre-constructing the heart.

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95.

Kehrer-Sawatzki H et al. (2003) Interphase FISH, the structure of reciprocal translocation chromosomes and physical mapping studies rule out the duplication of the NF1 gene at 17q11.2. A reply.

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96.

Colapietro P et al. (2003) NF1 exon 7 skipping and sequence alterations in exonic splice enhancers (ESEs) in a neurofibromatosis 1 patient.

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97.

Castle B et al. (2003) Evaluation of genotype-phenotype correlations in neurofibromatosis type 1.

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98.

Mosse YP et al. (2004) Germline PHOX2B mutation in hereditary neuroblastoma.

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99.

Zatkova A et al. (2004) Disruption of exonic splicing enhancer elements is the principal cause of exon skipping associated with seven nonsense or missense alleles of NF1.

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100.

Ling JQ et al. (2006) CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1.

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101.

Trovó-Marqui AB et al. (2006) Neurofibromin: a general outlook.

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102.

Upadhyaya M et al. (2007) An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation.

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103.

Sabbagh A et al. (2009) Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1.

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104.

Phan VT et al. (2010) The RasGAP proteins Ira2 and neurofibromin are negatively regulated by Gpb1 in yeast and ETEA in humans.

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105.

Lubeck BA et al. (2015) Cutting Edge: Codeletion of the Ras GTPase-Activating Proteins (RasGAPs) Neurofibromin 1 and p120 RasGAP in T Cells Results in the Development of T Cell Acute Lymphoblastic Leukemia.

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106.

NCBI article

NCBI 4763 [^]
107.

OMIM.ORG article

Omim 613113 [^]
108.

Orphanet article

Orphanet ID 123772 [^]
109.

Wikipedia article

Wikipedia EN (Neurofibromin) [^]
Update: April 29, 2019