Human Gene NF1 (ENST00000358273.9_9) from GENCODE V45lift37
Description: Homo sapiens neurofibromin 1 (NF1), transcript variant 1, mRNA. (from RefSeq NM_001042492) RefSeq Summary (NM_001042492): This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000358273.9_9 Gencode Gene: ENSG00000196712.20_15 Transcript (Including UTRs) Position: hg19 chr17:29,421,995-29,704,693 Size: 282,699 Total Exon Count: 58 Strand: + Coding Region Position: hg19 chr17:29,422,328-29,701,173 Size: 278,846 Coding Exon Count: 58
ID:NF1_HUMAN DESCRIPTION: RecName: Full=Neurofibromin; AltName: Full=Neurofibromatosis-related protein NF-1; Contains: RecName: Full=Neurofibromin truncated; FUNCTION: Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity. SUBUNIT: Interacts with HTR6 (PubMed:23027611). Interacts with SPRED2 (PubMed:34626534). INTERACTION: P21359; P05067: APP; NbExp=3; IntAct=EBI-1172917, EBI-77613; P21359; P01112: HRAS; NbExp=3; IntAct=EBI-1172917, EBI-350145; P21359; P34741: SDC2; NbExp=4; IntAct=EBI-1172917, EBI-1172957; P21359; Q7Z699: SPRED1; NbExp=6; IntAct=EBI-1172917, EBI-5235340; SUBCELLULAR LOCATION: Nucleus Nucleus, nucleolus Cell membrane TISSUE SPECIFICITY: Detected in brain, peripheral nerve, lung, colon and muscle. DOMAIN: Binds phospholipids via its C-terminal CRAL-TRIO domain. Binds primarily glycerophospholipids with monounsaturated C18:1 and/or C16:1 fatty acid moieties and a phosphatidylethanolamine or phosphatidylcholine headgroup. Has lesser affinity for lipids containing phosphatidylserine and phosphatidylinositol. RNA EDITING: Modified_positions=1306 ote=The stop codon (UGA) at position 1306 is created by RNA editing. Various levels of RNA editing occurs in peripheral nerve-sheath tumor samples (PNSTs) from patients with NF1. Preferentially observed in transcripts containing exon 23A.; DISEASE: Neurofibromatosis 1 (NF1) [MIM:162200]: A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors. te=The disease is caused by variants affecting the gene represented in this entry. DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. Note=The disease is caused by variants affecting the gene represented in this entry. DISEASE: Watson syndrome (WTSN) [MIM:193520]: A syndrome characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and intellectual disability. It is considered as an atypical form of neurofibromatosis. Note=The disease is caused by variants affecting the gene represented in this entry. DISEASE: Familial spinal neurofibromatosis (FSNF) [MIM:162210]: Considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors. Note=The disease is caused by variants affecting the gene represented in this entry. DISEASE: Neurofibromatosis-Noonan syndrome (NFNS) [MIM:601321]: Characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. te=The disease is caused by variants affecting the gene represented in this entry. DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis. CAUTION: Was originally thought to be associated with LEOPARD (LS), an autosomal dominant syndrome. SEQUENCE CAUTION: Sequence=AAA59923.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence=; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="https://atlasgeneticsoncology.org/gene/134/NF1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/nf1/"; WEB RESOURCE: Name=Mendelian genes neurofibromin 1 (NF1); Note=Leiden Open Variation Database (LOVD); URL="https://databases.lovd.nl/shared/genes/NF1";
aberrant splicing Messiaen LM et al. 1999, Exon 10b of the NF1 gene represents a mutational hotspot and harbors a recurrent missense mutation Y489C associated with aberrant splicing., Genetics in medicine. 1999 Sep-Oct;1(6):248-53.
[PubMed 11258625]
As exon 10b shows the highest mutation rate yet found in any of the 60 NF1 exons, it should be implemented with priority in mutation analysis.
autism Marui, T. et al. 2004, Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population., American journal of medical genetics Part B, Neuropsychiatric genetics. 2004 Nov;131(1):43-7.
[PubMed 15389774]
This may suggest an involvement of the NF1 locus in susceptibility to autism, although further investigations are recommended.
intestinal neuronal dysplasia type B (IND B) Bahuau M et al. 2000, Tandem duplication within the neurofibromatosis type 1 gene (NF1) and reciprocal t(15;16)(q26.3;q12.1) translocation in familial association of NF1 with intestinal neuronal dysplasia type B (IND B), Journal of medical genetics. 2000 Feb;37(2):146-50.
[PubMed 10712107]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P21359
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Gene Ontology (GO) Annotations with Structured Vocabulary
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
