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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NF2
NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor
Chromosome 22 Β· 22q12.2
NCBI Gene: 4771Ensembl: ENSG00000186575.20HGNC: HGNC:7773UniProt: A0A5K1VW66
410PubMed Papers
22Diseases
0Drugs
299Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTumor Suppressor
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
signaling adaptor activitymembranenegative regulation of cell population proliferationcytoplasmNF2-related schwannomatosisschwannomaschwannomatosisSMARCB1-related schwannomatosis
✦AI Summary

NF2 encodes Merlin, a tumor suppressor protein that plays a crucial role in regulating cell growth and death through multiple signaling pathways. Merlin functions as a central regulator of the Hippo signaling pathway, where it activates downstream effectors to suppress the oncogenic transcriptional co-activators YAP and TAZ 12. The protein also modulates ferroptosis, a form of programmed cell death, through intercellular E-cadherin interactions that activate NF2-Hippo signaling to suppress ferroptotic cell death 23. NF2 mutations are specifically associated with the development of schwannomas, meningiomas, and ependymomas, with distinct clinical presentations based on mutational status 45. NF2-deficient tumors, particularly meningiomas with NF2 loss, show increased susceptibility to ferroptosis-inducing therapies 3, while NF2-null schwannomas and meningiomas can be effectively targeted through inhibition of YAP/TAZ-driven TEAD activity 1. The protein's involvement extends to immune microenvironment regulation, where NF2 alterations influence immunotherapy outcomes in mesothelioma 6. Merlin's multifaceted role in growth control, apoptosis regulation, and tumor suppression makes it a critical target for therapeutic intervention in NF2-associated cancers.

Sources cited
1
NF2/Merlin involvement in multiple signaling pathways and association with schwannomas, meningiomas, and ependymomas
PMID: 38967126
2
NF2-Hippo signaling regulation of ferroptosis through E-cadherin-mediated intercellular interactions and YAP modulation
PMID: 31341276
3
NF2 loss increases meningioma susceptibility to ferroptosis and MEF2C regulation of NF2 and E-cadherin expression
PMID: 33984142
4
YAP/TAZ-driven TEAD activity as therapeutic target in NF2-null schwannoma and meningioma
PMID: 36148553
5
Distinct clinical presentations of NF2 mutant versus non-NF2 meningiomas
PMID: 23348505
6
NF2 alterations influence immune microenvironment and immunotherapy outcomes in mesothelioma
PMID: 40578509
Disease Associationsβ“˜22
NF2-related schwannomatosisOpen Targets
0.85Strong
schwannomaOpen Targets
0.69Moderate
schwannomatosisOpen Targets
0.68Moderate
SMARCB1-related schwannomatosisOpen Targets
0.65Moderate
neurofibromatosisOpen Targets
0.63Moderate
acoustic neuromaOpen Targets
0.62Moderate
Pleural MesotheliomaOpen Targets
0.61Moderate
familial meningiomaOpen Targets
0.61Moderate
hereditary neoplastic syndromeOpen Targets
0.57Moderate
Inherited cancer-predisposing syndromeOpen Targets
0.57Moderate
meningiomaOpen Targets
0.50Moderate
renal cell carcinomaOpen Targets
0.42Moderate
Malignant MesotheliomaOpen Targets
0.42Moderate
Meningothelial MeningiomaOpen Targets
0.38Weak
Chordoid MeningiomaOpen Targets
0.37Weak
Fibrous MeningiomaOpen Targets
0.37Weak
spinal cord ependymomaOpen Targets
0.37Weak
Transitional MeningiomaOpen Targets
0.37Weak
Psammomatous MeningiomaOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
Mesothelioma, malignantUniProt
Schwannomatosis, vestibularUniProt
Pathogenic Variants299
NM_000268.4(NF2):c.1447-1G>APathogenic
Neurofibromatosis, type 2
β˜…β˜…β˜†β˜†2026
NM_000268.4(NF2):c.586C>T (p.Arg196Ter)Pathogenic
Neurofibromatosis, type 2|not provided|Hereditary cancer-predisposing syndrome|Familial meningioma;Neurofibromatosis, type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 196
NM_000268.4(NF2):c.810+1G>APathogenic
not provided|Neurofibromatosis, type 2|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025
NM_000268.4(NF2):c.240+1G>TPathogenic
Neurofibromatosis, type 2|Acoustic neuroma|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025
NM_000268.4(NF2):c.1396C>T (p.Arg466Ter)Pathogenic
Neurofibromatosis, type 2|not provided|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 466
NM_000268.4(NF2):c.1550T>C (p.Leu517Pro)Pathogenic
Neurofibromatosis, type 2|not provided|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 517
NM_000268.4(NF2):c.600-2A>GPathogenic
Neurofibromatosis, type 2|not provided
β˜…β˜…β˜†β˜†2025
NM_000268.4(NF2):c.774G>A (p.Trp258Ter)Pathogenic
Neurofibromatosis, type 2|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 258
NM_000268.4(NF2):c.784C>T (p.Arg262Ter)Pathogenic
Neurofibromatosis, type 2|not provided|Meningioma
β˜…β˜…β˜†β˜†2025β†’ Residue 262
NM_000268.4(NF2):c.364-2A>GLikely pathogenic
Neurofibromatosis, type 2|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025
NM_000268.4(NF2):c.41_42del (p.Leu14fs)Pathogenic
not provided|Neurofibromatosis, type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 14
NM_000268.4(NF2):c.169C>T (p.Arg57Ter)Pathogenic
Meningioma|not provided|Neurofibromatosis, type 2|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 57
NM_000268.4(NF2):c.1229dup (p.Arg411fs)Pathogenic
Neurofibromatosis, type 2|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 411
NM_000268.4(NF2):c.240+1G>CPathogenic
Neurofibromatosis, type 2|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025
NM_000268.4(NF2):c.1219C>T (p.Gln407Ter)Pathogenic
Neurofibromatosis, type 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 407
NM_000268.4(NF2):c.516+1G>APathogenic
Neurofibromatosis, type 2|not provided|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025
NM_000268.4(NF2):c.193C>T (p.Gln65Ter)Pathogenic
Neurofibromatosis, type 2|Meningioma
β˜…β˜…β˜†β˜†2025β†’ Residue 65
NM_000268.4(NF2):c.592C>T (p.Arg198Ter)Pathogenic
Neurofibromatosis, type 2|not provided|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 198
NM_000268.4(NF2):c.1579G>T (p.Glu527Ter)Pathogenic
Neurofibromatosis, type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 527
NM_000268.4(NF2):c.1737+2T>CPathogenic
Neurofibromatosis, type 2|Hereditary cancer-predisposing syndrome
β˜…β˜…β˜†β˜†2025
View on ClinVar β†—
Related Genes
PATJProtein interaction100%AMOTProtein interaction100%CTNNB1Protein interaction100%EGFRProtein interaction100%LATS1Protein interaction100%SMARCB1Protein interaction98%
Tissue Expression6 tissues
Heart
100%
Brain
87%
Lung
54%
Ovary
51%
Liver
49%
Bone Marrow
47%
Gene Interaction Network
Click a node to explore
NF2PATJAMOTCTNNB1EGFRLATS1SMARCB1
PROTEIN STRUCTURE
Preparing viewer…
PDB7LWH Β· 1.61 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.19Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.10 [0.06–0.19]
RankingsWhere NF2 stands among ~20K protein-coding genes
  • #704of 20,598
    Most Researched410 Β· top 5%
  • #206of 5,498
    Most Pathogenic Variants299 Β· top 5%
  • #377of 17,882
    Most Constrained (LOEUF)0.19 Β· top 5%
Genes detectedNF2
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
The molecular biology of NF2/Merlin on tumorigenesis and development.
PMID: 38967126
FASEB J Β· 2024
1.00
2
Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling.
PMID: 31341276
Nature Β· 2019
0.90
3
MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma.
PMID: 33984142
Neuro Oncol Β· 2021
0.80
4
Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma.
PMID: 36148553
Brain Β· 2023
0.70
5
Gene therapy for diffuse pleural mesotheliomas in preclinical models by concurrent expression of NF2 and SuperHippo.
PMID: 39368484
Cell Rep Med Β· 2024
0.68