Cited by 1,095Neurofibromatosis and Schwannoma CasesProtein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase Signaling

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The neurofibromatosis type 1 gene encodes a protein related to GAP

Xu, Gangfeng, O'Connell, Peter, Viskochil, David, Cawthon, Richard, Robertson, Margaret, Culver, Melanie, Dunn, Diane, Stevens, Jeff, Gesteland, Ray, White, Ray, Weiss, Robert·1990·Cell

DOI 10.1016/0092-8674(90)90024-9

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Abstract

cDNA walking and sequencing have extended the open reading frame for the neurofibromatosis type 1 gene (NF1). The new sequence now predicts 2485 amino acids of the NF1 peptide. A 360 residue region of the new peptide shows significant similarity to the known catalytic domains of both human and bovine GAP (GTPase activating protein). A much broader region, centered around this same 360 amino acid sequence, is strikingly similar to the yeast IRA1 product, which has a similar amino acid sequence and functional homology to mammalian GAP. This evidence suggests that NF1 encodes a cytoplasmic GAP-like protein that may be involved in the control of cell growth by interacting with proteins such as the RAS gene product. Mapping of the cDNA clones has confirmed that NF1 spans a t(1;17) translocation mutation and that three active genes lie within an intron of NF1, but in opposite orientation.

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Self-citation
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Background
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Background
Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas. A study of 226 cases*
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BackgroundInfluential
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Background
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Novel NF1 gene mutation in a Japanese patient with neurofibromatosis type 1 and a gastrointestinal stromal tumor
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A machine learning classifier trained on cancer transcriptomes detects NF1 inactivation signal in glioblastoma
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“One such alteration is the loss of neurofibromin 1 (NF1), an important tumor suppressor that regulates the activity of RAS GTPases [1, 2].”
Background
Complete Human NF1 cDNA Sequence: Two Alternatively Spliced mRNAs and Absence of Expression in a Neuroblastoma Line
Bernards, A., Haase, V. H., Murthy, A. E., Menon, A. G., Hannigan, G. E., & Gusella, J. F. (1992) · DNA and Cell Biology · doi:10.1089/dna.1992.11.727 · Cited by 34
“…(Cawthon et al, 1990; Wallace et al, 1990; Xu et al, 1990a) have revealed that the gene encodes a large protein, termed neurofibromin, with a GTPase-activating (GAP) domain related to the yeast IRAI and IRA2 genes (Ballester et al, 1990; Buchberg et al, 1990; Martin et al, 1990; Xu et al, 1990a,b).”
Genetic Alterations in a Malignant Schwannoma from a Patient with Neurofibromatosis (NF1)
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Self-citation
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RETRACTED: microRNA-107 functions as a candidate tumor suppressor gene in renal clear cell carcinoma involving multiple genes
Song, N., Ma, X., Li, H., Zhang, Y., Wang, X., Zhou, P., & Zhang, X. (2015) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2015.02.003 · Cited by 33
“*P(NOTCH2) o 0.05, n ¼ 3; **P(NOTCH2) 4 0.05, n¼ 3; *P o 0.05 ¼ 0.0004, n ¼ 3; **P(NF1) 4 0.05, n ¼ 3; *P(VEGFA) o 0.05, n ¼ 3; **P(VEGFA) o 0.05, n ¼ 3; *P(EIF5) o 0.05, n ¼ 3; **P(EIF5) o 0.05, n ¼ 3.”
BackgroundInfluential
Retracted
Peripheral neural sheath tumors (PNST)—What a radiologist should know
Kubiena, H., Entner, T., Schmidt, M., & Frey, M. (2011) · European Journal of Radiology · doi:10.1016/j.ejrad.2011.04.037 · Cited by 33
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Neurofibromatosis Type 1
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“This type of transcript has been demonstrated in studies of the neurofibromatosis type 1 gene (NF1) in which three other genes are embedded in an intron and transcribed from the complimentary strand of NF1 (Xu et al. 1990; Viskochil et al. 1991).”
Background
Genetic diagnosis of neurofibromatosis type 1: targeted next- generation sequencing with Multiple Ligation-Dependent Probe Amplification analysis
Chou, Y. W., Hung, T.-C., Lin, Y.-T., Cheng, H.-W., Lin, J.-L., Lin, C.-H., Yu, C.-C., Chen, K., Yeh, T., & Chen, Y.-R. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0474-9 · Cited by 36
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Thirty-Nine Novel Neurofibromatosis 1 (NF1)Gene Mutations Identified in Slovak Patients
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“It was shown in 1998 that mutations in the NF1 GAPrelated domain (GRD) (Martin et al., 1990; Xu et al., 1990) completely disable GAP activity (Klose et al.”
BackgroundInfluential
Surgical Management of Spinal Cord Compression from Plexiform Neurofibromas in Patients with Neurofibromatosis 1
Pollack, I. F., Çolak, A., Fitz, C. R., Wiener, E. S., Moreland, M. S., & Mulvihill, J. J. (1998) · Neurosurgery · doi:10.1097/00006123-199808000-00038 · Cited by 32
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Characterization of a 7.6-Mb germline deletion encompassing the NF1 locus and about a hundred genes in an NF1 contiguous gene syndrome patient
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Drosophila Arginase Is Produced from a Nonvital Gene That Contains the elav Locus within Its Third Intron
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Hypokalemic Rhabdomyolysis due to WDHA Syndrome Caused by VIP-producing Composite Pheochromocytoma: A Case in Neurofibromatosis Type 1
Onozawa, M., Fukuhara, T., Minoguchi, M., Takahata, M., Yamämoto, Y., Miyake, T., Kanagawa, K., Kanda, M., & Maekawa, I. (2005) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyi139 · Cited by 32
“Neurofibromin, the product of NF1, contains a region homologous to mammalian RasGTPase-activating proteins that function as negative regulators of Ras by accelerating the conversion of Ras-GTP to Ras-GDP ( 21 ).”
Background
Tumor Suppressor Genes and Human Cancer
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Neurofibromatosis Type 1 Alternative Splicing Is a Key Regulator of Ras Signaling in Neurons
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Visual evoked potentials in children with neurofibromatosis type 1
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Authors: Xu, G., O'Connell, P., Viskochil, D., Cawthon, R., Robertson, M., Culver, M., Dunn, D., Stevens, J., Gesteland, R., White, R., & Weiss, R.
Affiliations: Howard Hughes Medical Institute (US)
University of Utah (US)
ORCID: O'Connell, Peter
Viskochil, David
Cawthon, Richard
Culver, Melanie
Stevens, Jeff
Weiss, Robert
Venue: Cell
Publisher: Elsevier BV
Published: 1990-08
Volume: 62
Issue: 3
Pages: 599-608
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(90)90024-9
OpenAlex: W2159096148
Cited by: 1,095
References: 42
Citations by year: 2026: 7 · 2025: 13 · 2024: 19 · 2023: 19 · 2022: 22 · 2021: 22 · 2020: 22 · 2019: 18 · 2018: 22 · 2017: 17 · 2016: 19 · 2015: 21 · 2014: 24 · 2013: 24 · 2012: 45
FWCI: 70.71
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
U.S. Department of Energy
Topics: Health Sciences › Medicine › Clinical Neurology › Neurofibromatosis and Schwannoma Cases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: neurofibromatosis type 1, NF1 gene, GTPase-activating protein, Ras, open reading frames, cDNA cloning, cell growth regulation, protein homology
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cattle, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 17, Cloning, Molecular, Genes, Humans, Information Systems, Molecular Sequence Data, Neurofibromatosis 1, Proteins, Sequence Homology, Nucleic Acid, Translocation, Genetic, Oligonucleotide Probes, Gene Library, Polymerase Chain Reaction, GTPase-Activating Proteins, ras GTPase-Activating Proteins, Neurofibromin 1

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The neurofibromatosis type 1 gene encodes a protein related to GAP

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