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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NF1
neurofibromin 1
Chromosome 17 Β· 17q11.2
NCBI Gene: 4763Ensembl: ENSG00000196712.20HGNC: HGNC:7765UniProt: P21359
637PubMed Papers
26Diseases
0Drugs
5,462Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTumor Suppressor
RESEARCH IMPACT
Highly StudiedVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
negative regulation of cell migrationnegative regulation of MAPK cascadepositive regulation of GTPase activityGTPase activator activityneurofibromatosis type 1neurofibromatosis-Noonan syndromeneurofibromatosisJuvenile Myelomonocytic Leukemia
✦AI Summary

NF1 (neurofibromin 1) is a tumor suppressor gene located on chromosome 17.2 that encodes neurofibromin, a critical regulator of cellular growth and proliferation. The primary function of neurofibromin is to stimulate GTPase activity of the proto-oncogene Ras, thereby downregulating the RAS/MAPK signaling pathway 12. Additionally, neurofibromin controls cell growth through regulation of cyclic adenosine monophosphate (AMP) 1. Beyond Ras regulation, NF1 loss impairs Schwann cell differentiation by inducing a persistent stem-like state that expands progenitor pools 3. Constitutional NF1 mutations cause neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder characterized by benign peripheral nerve sheath tumors (neurofibromas), cafΓ©-au-lait macules, and predisposition to malignancies including breast cancer and leukemia 14. Somatic NF1 mutations also occur frequently in sporadic cancers (melanoma, lung, colorectal, ovarian, glioblastoma), indicating broader roles in cancer pathogenesis 2. NF1 mutations contribute to drug resistance in melanoma, lung, and breast cancers 2. Comprehensive RNA analysis achieves ~96-97% diagnostic sensitivity in classically affected NF1 patients 5, and recent therapeutic approaches including econazole have shown promise in preclinical models of cutaneous neurofibromas 6.

Sources cited
1
NF1 gene location, neurofibromin function in controlling cell growth through Ras and cAMP regulation, and hallmark neurofibroma pathology
PMID: 23931823
2
NF1 loss impairs Schwann cell differentiation and induces persistent stem-like state in progenitor cells to promote neurofibroma development
PMID: 33108355
3
Neurofibromin's major function to downregulate RAS, somatic NF1 mutations in various cancers, and role in drug resistance
PMID: 28637487
4
Diagnostic sensitivity of RNA analysis (~96-97%) in NF1 patients meeting NIH criteria
PMID: 27322474
5
Econazole as therapeutic candidate selectively inducing cell death in NF1-homozygous mutant tumor cells
PMID: 38086379
6
NF1 as common dominantly inherited genetic disorder with age-dependent phenotypic expression and genotype-phenotype correlations
PMID: 31717729
Disease Associationsβ“˜26
neurofibromatosis type 1Open Targets
0.88Strong
neurofibromatosis-Noonan syndromeOpen Targets
0.83Strong
neurofibromatosisOpen Targets
0.82Strong
Juvenile Myelomonocytic LeukemiaOpen Targets
0.77Strong
Watson syndromeOpen Targets
0.75Strong
neurofibromatosis, familial spinalOpen Targets
0.72Strong
malignant peripheral nerve sheath tumorOpen Targets
0.69Moderate
Neurofibromatosis type 1 due to NF1mutation or intragenic deletionOpen Targets
0.67Moderate
Tibial pseudarthrosisOpen Targets
0.67Moderate
neurocutaneous syndromeOpen Targets
0.66Moderate
neurofibromaOpen Targets
0.66Moderate
rhabdomyosarcomaOpen Targets
0.64Moderate
neoplasmOpen Targets
0.62Moderate
melanomaOpen Targets
0.61Moderate
urinary bladder carcinomaOpen Targets
0.61Moderate
urinary bladder cancerOpen Targets
0.61Moderate
benign neoplasmOpen Targets
0.60Moderate
nervous system diseaseOpen Targets
0.60Moderate
respiratory system diseaseOpen Targets
0.59Moderate
nervous system benign neoplasmOpen Targets
0.58Moderate
Colorectal cancerUniProt
Familial spinal neurofibromatosisUniProt
Leukemia, juvenile myelomonocyticUniProt
Neurofibromatosis 1UniProt
Neurofibromatosis-Noonan syndromeUniProt
Watson syndromeUniProt
Pathogenic Variants5,462
NM_001042492.3(NF1):c.1527+4_1527+7delPathogenic
Neurofibromatosis, type 1|not provided|Cardiovascular phenotype;Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2026
NM_001042492.3(NF1):c.2850+1G>TPathogenic
not provided|Neurofibromatosis, type 1|Hereditary cancer-predisposing syndrome;Cardiovascular phenotype
β˜…β˜…β˜†β˜†2026
NM_001042492.3(NF1):c.1260+1G>TPathogenic
Neurofibromatosis, type 1|Cardiovascular phenotype;Hereditary cancer-predisposing syndrome|not provided
β˜…β˜…β˜†β˜†2026
NM_001042492.3(NF1):c.5971dup (p.Ser1991fs)Pathogenic
Neurofibromatosis, type 1
β˜…β˜…β˜†β˜†2026β†’ Residue 1991
NM_001042492.3(NF1):c.1541_1542del (p.Gln514fs)Pathogenic
Neurofibromatosis, type 1|not provided|Hereditary cancer-predisposing syndrome|Juvenile myelomonocytic leukemia|Neurofibromatosis, familial spinal;Neurofibromatosis-Noonan syndrome;CafΓ©-au-lait macules with pulmonary stenosis;Juvenile myelomonocytic leukemia;Neurofibromatosis, type 1|NF1-related disorder|Neurofibromatosis-Noonan syndrome
β˜…β˜…β˜†β˜†2026β†’ Residue 514
NM_001042492.3(NF1):c.7153AACTTT[1] (p.2385NF[1])Pathogenic
Neurofibromatosis, type 1|not provided|Tibial pseudarthrosis;Neurofibromatosis, type 1|Rhabdomyosarcoma|Hereditary cancer-predisposing syndrome;Cardiovascular phenotype|NF1-related disorder|Neurofibromatosis-Noonan syndrome;CafΓ©-au-lait macules with pulmonary stenosis;Neurofibromatosis, familial spinal;Juvenile myelomonocytic leukemia;Neurofibromatosis, type 1
β˜…β˜…β˜†β˜†2026
NM_001042492.3(NF1):c.499_502del (p.Cys167fs)Pathogenic
Inborn genetic diseases|Neurofibromatosis, type 1|not provided|Neurofibromatosis, type 1;Tibial pseudarthrosis|Cardiovascular phenotype;Hereditary cancer-predisposing syndrome|CafΓ©-au-lait macules with pulmonary stenosis|Embryonal rhabdomyosarcoma|Neurofibromatosis, familial spinal;Neurofibromatosis, type 1;Neurofibromatosis-Noonan syndrome;CafΓ©-au-lait macules with pulmonary stenosis;Juvenile myelomonocytic leukemia|See cases
β˜…β˜…β˜†β˜†2026β†’ Residue 167
NM_001042492.3(NF1):c.4382T>A (p.Met1461Lys)Pathogenic
Neurofibromatosis, type 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 1461
NM_001042492.3(NF1):c.7300C>T (p.Gln2434Ter)Pathogenic
Neurofibromatosis, type 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 2434
NM_001042492.3(NF1):c.6772C>T (p.Arg2258Ter)Pathogenic
Hereditary cancer-predisposing syndrome|Neurofibromatosis, type 1|not provided|Tibial pseudarthrosis;Neurofibromatosis, type 1|CafΓ©-au-lait macules with pulmonary stenosis;Juvenile myelomonocytic leukemia;Neurofibromatosis-Noonan syndrome;Neurofibromatosis, familial spinal;Neurofibromatosis, type 1|Cardiovascular phenotype;Hereditary cancer-predisposing syndrome|CafΓ©-au-lait macules with pulmonary stenosis|NF1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 2258
NM_001042492.3(NF1):c.4985G>A (p.Trp1662Ter)Pathogenic
Neurofibromatosis, type 1|Rhabdomyosarcoma|Cardiovascular phenotype;Hereditary cancer-predisposing syndrome|not provided|CafΓ©-au-lait macules with pulmonary stenosis;Neurofibromatosis, familial spinal;Juvenile myelomonocytic leukemia;Neurofibromatosis-Noonan syndrome;Neurofibromatosis, type 1
β˜…β˜…β˜†β˜†2026β†’ Residue 1662
NM_001042492.3(NF1):c.6430G>T (p.Glu2144Ter)Pathogenic
not provided|Neurofibromatosis, type 1
β˜…β˜…β˜†β˜†2026β†’ Residue 2144
NM_001042492.3(NF1):c.1660C>T (p.Gln554Ter)Pathogenic
Neurofibromatosis, type 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 554
NM_001042492.3(NF1):c.5327C>G (p.Ser1776Ter)Pathogenic
Neurofibromatosis-Noonan syndrome;CafΓ©-au-lait macules with pulmonary stenosis;Neurofibromatosis, type 1|Neurofibromatosis, type 1|not provided|Hereditary cancer-predisposing syndrome;Cardiovascular phenotype
β˜…β˜…β˜†β˜†2026β†’ Residue 1776
NM_001042492.3(NF1):c.3520C>T (p.Gln1174Ter)Pathogenic
Rhabdomyosarcoma|Neurofibromatosis, type 1|not provided|NF1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 1174
NM_001042492.3(NF1):c.3892C>T (p.Gln1298Ter)Pathogenic
Neurofibromatosis, type 1|Hereditary cancer-predisposing syndrome;Cardiovascular phenotype|not provided|CafΓ©-au-lait macules with pulmonary stenosis;Neurofibromatosis, familial spinal;Neurofibromatosis, type 1;Neurofibromatosis-Noonan syndrome;Juvenile myelomonocytic leukemia
β˜…β˜…β˜†β˜†2026β†’ Residue 1298
NM_001042492.3(NF1):c.1949T>G (p.Leu650Ter)Pathogenic
Neurofibromatosis, type 1
β˜…β˜…β˜†β˜†2026β†’ Residue 650
NM_001042492.3(NF1):c.1721+3A>GPathogenic
Neurofibroma;Cafe au lait spots, multiple|Hereditary cancer-predisposing syndrome|Neurofibromatosis, type 1|Optic nerve glioma;Cafe au lait spots, multiple|not provided|Juvenile myelomonocytic leukemia
β˜…β˜…β˜†β˜†2026
NM_001042492.3(NF1):c.4824T>G (p.Tyr1608Ter)Pathogenic
Neurofibromatosis, type 1|Cardiovascular phenotype;Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2026β†’ Residue 1608
NM_001042492.3(NF1):c.6643-2A>GPathogenic
Neurofibromatosis, type 1|Cardiovascular phenotype;Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2026
View on ClinVar β†—
Related Genes
MSH2Protein interaction100%PMS2Protein interaction100%MSH6Protein interaction100%ATRXProtein interaction100%ATMProtein interaction100%HRASProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
76%
Ovary
48%
Lung
38%
Liver
32%
Bone Marrow
30%
Gene Interaction Network
Click a node to explore
NF1MSH2PMS2MSH6ATRXATMHRAS
PROTEIN STRUCTURE
Preparing viewer…
PDB6OB3 Β· 2.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.45Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.38 [0.33–0.45]
RankingsWhere NF1 stands among ~20K protein-coding genes
  • #355of 20,598
    Most Researched637 Β· top 5%
  • #3of 5,498
    Most Pathogenic Variants5,462 Β· top 1%
  • #2,497of 17,882
    Most Constrained (LOEUF)0.45 Β· top quartile
Genes detectedNF1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Neurofibromatosis type 1 (NF1): diagnosis and management.
PMID: 23931823
Handb Clin Neurol Β· 2013
1.00
2
Humanized neurofibroma model from induced pluripotent stem cells delineates tumor pathogenesis and developmental origins.
PMID: 33108355
J Clin Invest Β· 2021
0.90
3
The Role of Artificial Intelligence in Identifying
PMID: 40428382
Genes (Basel) Β· 2025
0.86
4
Neurofibromatosis type 1.
PMID: 7811422
Genet Couns Β· 1994
0.84
5
The NF1 tumor suppressor regulates PD-L1 and immune evasion in melanoma.
PMID: 40023845
Cell Rep Β· 2025
0.80