NF1 (neurofibromin 1)
2006-02-01 Katharina Wimmer AffiliationMedizinische Universitüt Wien, Institut für Humangenetik, Klinischen Instituts für Medizinische und Chemische Labordiagnostik (KIMCL), Wühringerstrasse 10, 1090 Wien, è_sterreich, Austria
DNA/RNA
Description
60 exons (57 constitutive, 3 alternative); spans 280 kb; presence of 3 cryptic genes: OMGP, EVI2A, and EVI2B (overlapping genes), hidden (!) within NF1 intron 27b with an opposite transcription direction.
Transcription
at least 4 alternate splicings; ~ 9.0 kb mRNA complete cds; coding sequence: CDS 198..8717
Proteins
Description
the protein has been called neurofibromin; 2818 and 2839 amino acids (type-1 and type-2 isoform)
Expression
is tissue and development stage specific
Function
GTPase activating protein (GAP) interacting with p21RAS -> tumour suppressor.
Homology
other (GAP); IRA1 and 2, the yeast inhibitors of p21RAS
Mutations
Germinal
large submicroscopic deletions in 5-10% of cases, translocations rare and point mutations in app. 85-90% of cases; widely dispersed, with no clustering, unusual splicing mutations yield difficulties in molecular genetic testing, truncating effect in large majority of cases.
Somatic
second inactivating mutation occurs in the Schwann cell of benign neurofibromas; additional genetic alterations in this cell lead to malignant transformation; the spectrum of inactivating somatic mutation not fully elucidated, LOH owing to copy number loss and mitotic recombination, point mutations; another inactivating process may involve RNA editing (for the second allele), which gives rise to a truncated neurofibromin having lost its GAP activity.
Implicated in
Entity name
Disease
autosomal dominant cancer prone disease; neurofibromatosis type 1 (NF1: the same symbol is used for the disease neurofibromatosis type 1 and the gene neurofibromin 1) is an hamartoneoplastic syndrome.
Entity name
Watson syndrome
Disease
autosomal dominant disease with cardiac malformations, and, as is found in von Recklinghausen neurofibromatosis, low normal intelligence, café-au-lait spots, and neurofibromas but to a lesser extend.
Oncogenesis
in accordance with the two-hit model for neoplasia, as is found in retinoblastoma.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 1770531 | 1991 | Watson syndrome: is it a subtype of type 1 neurofibromatosis? | Allanson JE et al |
| 9012403 | 1997 | A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors. | Cappione AJ et al |
| 2114220 | 1990 | A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. | Cawthon RM et al |
| 16380919 | 2005 | NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome. | De Luca A et al |
| 15257518 | 2004 | High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1) with microdeletions caused by somatic recombination of the JJAZ1 gene. | Kehrer-Sawatzki H et al |
| 14722914 | 2004 | Screening 500 unselected neurofibromatosis 1 patients for deletions of the NF1 gene. | Kluwe L et al |
| 8499945 | 1993 | Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. | Legius E et al |
| 7774960 | 1995 | Genomic organization of the neurofibromatosis 1 gene (NF1). | Li Y et al |
| 10862084 | 2000 | Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. | Messiaen LM et al |
| 7595647 | 1995 | Genetic and epigenetic mechanisms in the pathogenesis of neurofibromatosis type I. | Metheny LJ et al |
| 11431704 | 2001 | Mitotic recombination effects homozygosity for NF1 germline mutations in neurofibromas. | Serra E et al |
| 8302341 | 1994 | Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. | Shannon KM et al |
| 8317503 | 1993 | Tandem duplication within a neurofibromatosis type 1 (NF1) gene exon in a family with features of Watson syndrome and Noonan syndrome. | Tassabehji M et al |
| 1694727 | 1990 | Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. | Viskochil D et al |
| 2134734 | 1990 | Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. | Wallace MR et al |
| 16283621 | 2006 | Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients. | Wimmer K et al |
Other Information
Locus ID:
NCBI: 4763
MIM: 613113
HGNC: 7765
Ensembl: ENSG00000196712
Variants:
dbSNP: 4763
ClinVar: 4763
TCGA: ENSG00000196712
COSMIC: NF1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37301319 | 2024 | Distinct Transcriptional Profiles in the Different Phenotypes of Neurofibroma from the Same Subject with Neurofibromatosis 1. | 0 |
| 37945316 | 2024 | Biallelic inactivation of the NF1 tumour suppressor gene in juvenile myelomonocytic leukaemia: Genetic evidence of driver function and implications for diagnostic workup. | 0 |
| 38127282 | 2024 | Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression. | 3 |
| 38154814 | 2024 | Breast cancer risk in NF1-deleted patients. | 0 |
| 38216123 | 2024 | NF1 deficiency drives metabolic reprogramming in ER+ breast cancer. | 2 |
| 38448021 | 2024 | [Analysis of NF1 gene variants in a Chinese pedigree and a sporadic patient with Neurofibromatosis type 1]. | 0 |
| 38603649 | 2024 | NF1-Driven Rhabdomyosarcoma Phenotypes: A Comparative Clinical and Molecular Study of NF1-Mutant Rhabdomyosarcoma and NF1-Associated Malignant Triton Tumor. | 0 |
| 38874808 | 2024 | Genetic/epigenetic effects in NF1 microdeletion syndrome: beyond the haploinsufficiency, looking at the contribution of not deleted genes. | 0 |
| 38924432 | 2024 | MEK-SHP2 inhibition prevents tibial pseudarthrosis caused by NF1 loss in Schwann cells and skeletal stem/progenitor cells. | 0 |
| 38954284 | 2024 | A Comprehensive Overview of NF1 Mutations in Iranian Patients. | 0 |
| 37301319 | 2024 | Distinct Transcriptional Profiles in the Different Phenotypes of Neurofibroma from the Same Subject with Neurofibromatosis 1. | 0 |
| 37945316 | 2024 | Biallelic inactivation of the NF1 tumour suppressor gene in juvenile myelomonocytic leukaemia: Genetic evidence of driver function and implications for diagnostic workup. | 0 |
| 38127282 | 2024 | Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression. | 3 |
| 38154814 | 2024 | Breast cancer risk in NF1-deleted patients. | 0 |
| 38216123 | 2024 | NF1 deficiency drives metabolic reprogramming in ER+ breast cancer. | 2 |
Citation
Katharina Wimmer
NF1 (neurofibromin 1)
Atlas Genet Cytogenet Oncol Haematol. 2006-02-01
Online version: http://atlasgeneticsoncology.org/gene/134/nf1
Historical Card
1997-09-01 NF1 (neurofibromin 1) by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
