# NF1 (neurofibromin)

Source: https://onco.cc/targets/nf1/  
OnCo record `nf1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

NF1 makes neurofibromin, the protein that switches RAS off. People born with one faulty copy develop neurofibromatosis type 1, whose plexiform neurofibromas are now treated with the MEK inhibitors selumetinib and mirdametinib, which cut the RAS signal one step down.

## Summary

NF1 (chromosome 17q11.2) encodes neurofibromin, a RAS GTPase-activating protein that stimulates RAS' hydrolysis of GTP and so returns it to the off state; it has high affinity for RAS but low specific activity and is thought to be a regulator of RAS activity (UniProt P21359). Loss of neurofibromin leaves RAS active without a RAS mutation. In OnCo, NF1 is the germline condition behind the plexiform neurofibromas for which selumetinib (FDA, April 2020, children aged 2 and over, on the SPRINT trial) and mirdametinib (FDA, February 2025, adults and children aged 2 and over, on the ReNeu trial) are approved; both are non-ATP-competitive MEK1/2 inhibitors that lower ERK signalling in NF1-deficient Schwann-lineage cells, and the MEK target record lists NF1-associated plexiform neurofibroma and paediatric low-grade glioma among the settings.

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: neurofibromin; neurofibromin 1
- Tags: wave5-target
- Symbol: NF1
- Class: tumor-suppressor
- Biology: A tumour suppressor with no drug of its own: therapy targets the pathway it normally restrains. The two approved drugs are recorded with response rates in the corpus (two-thirds of 50 children in SPRINT stratum 1; 41% in ReNeu), and the MEK record notes that MEK inhibitors are selected on upstream BRAF, NF1 or RAS status rather than on MEK itself.
- Where found: Neurofibromatosis type 1 (plexiform neurofibromas; NF1-associated low-grade glioma); Non-small-cell lung cancer: inactivating mutation 8-12%

## Notes

- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
- Lung cancer: inactivated in 8 to 12% of adenocarcinomas and 11.6% of squamous tumours (cBioPortal). It releases RAS without a RAS mutation, and with MET, ERBB2 and RIT1 it accounts for 13% of adenocarcinomas, concentrated in those with no other activated oncogene (Cancer Genome Atlas Research Network 2014).

## Sources

- HGNC HGNC:7765: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7765
- UniProt P21359: https://www.uniprot.org/uniprotkb/P21359/entry
- NCBI Gene 4763: https://www.ncbi.nlm.nih.gov/gene/4763

## Connected records

- drugs: [Mirdametinib](https://onco.cc/drugs/mirdametinib/), [Selumetinib](https://onco.cc/drugs/selumetinib/)
- targets: [KRAS](https://onco.cc/targets/kras/), [MEK1/2](https://onco.cc/targets/mek/), [NRAS](https://onco.cc/targets/nras/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Optic pathway glioma](https://onco.cc/cancers/optic-pathway-glioma/), [Somatostatinoma](https://onco.cc/cancers/somatostatinoma/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- pathways: [Drivers, passengers & the two-hit model](https://onco.cc/pathways/oncogene-activation-two-hit/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- key papers: [Comprehensive molecular profiling of lung adenocarcinoma](https://onco.cc/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/), [Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas](https://onco.cc/key-papers/paper-campbell-pan-lung-somatic-alterations-nat-genet-2016/), [Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations](https://onco.cc/key-papers/paper-wardell-biliary-drivers-germline-j-hepatol-2018/), [Genomic characterization of metastatic breast cancers](https://onco.cc/key-papers/paper-bertucci-metastatic-breast-genomics-nature-2019/), [Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis](https://onco.cc/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/)

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