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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.
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.
In plain words · 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.
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.
A tumour suppressor with no drug of its own: therapy targets the pathway it normally restrains.
No product in this corpus aims at NF1 (neurofibromin) yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
First described 1990. Earliest sequence paper UniProt cites for the protein: Wallace M.R. et al, Science, 1990, "Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients". Source.
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.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 8-12% | Inactivating mutation | cBioPortal: 206 of 2,653, 7.8%, in luad_mskcc_2023_met_organotropism; 67 of 915, 7.3%, in lung_msk_2017; 66 of 566, 11.7%, in luad_tcga_pan_can_atlas_2018; 27 of 230, 11.7%, in luad_tcga_pub; 25 of 240, 10.4%, in nsclc_pd1_msk_2018; 10 of 302, 3.3%, in luad_oncosg_2020. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Re-biopsy and re-sequencing at relapse can find repair defects and a higher mutation burden that the primary did not show, which matters for PARP inhibitor and immunotherapy eligibility in metastatic TNBC.
The germline finding is the practical lesson: a meaningful minority of biliary cancer patients carry inherited repair-gene mutations that matter for PARP inhibitor eligibility and for their relatives, which argues for germline testing alongside tumour sequencing.
This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.
It is the empirical basis for treating the two histologies as separate diseases for targeted therapy and as one disease for immunotherapy, which is exactly how they are treated.
It is the reference table the field still argues against, and it made two practical points that outlived it: a tumour with no driver on a standard panel usually has one that the panel did not look for, and pathway activity measured on protein does not follow from the mutation list.
Query for this target: (TITLE:"NF1" OR ABSTRACT:"NF1" OR TITLE:"neurofibromin" OR ABSTRACT:"neurofibromin" OR TITLE:"neurofibromin 1" OR ABSTRACT:"neurofibromin 1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NF1 (neurofibromin), not a curated reading list.
Shares MEK1/2, KRAS, Small-molecule kinase inhibitors, Non-small-cell lung cancer and the tag wave5-target.
Shares RAS / RAF / MEK / ERK (MAPK), KRAS, Small-molecule kinase inhibitors, Non-small-cell lung cancer and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.
Shares Non-small-cell lung cancer and the tag wave5-target.
Shares Non-small-cell lung cancer and the tag wave5-target.
Shares Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas, Comprehensive molecular profiling of lung adenocarcinoma, Non-small-cell lung cancer.