NF1 (neurofibromin)
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
A tumour suppressor with no drug of its own: therapy targets the pathway it normally restrains.
- 3 · How drugs use it
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).
External identifiers
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.
- Neurofibromatosis type 1 (plexiform neurofibromas; NF1-associated low-grade glioma)
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery 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.
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