NF2

Chr 22AD

NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor

Also known as: ACN, BANF, SCH, SWNV, merlin-1

NCBI Gene: 4771ENSG00000186575UniProt: P35240

This gene encodes a protein that is similar to some members of the ERM (ezrin, radixin, moesin) family of proteins that link cytoskeletal components with proteins in the cell membrane. The encoded protein is involved in regulation of contact-dependent inhibition of cell proliferation and functions in cell-cell adhesion and transmembrane signaling. The encoded protein has been shown to interact with cell-surface proteins, proteins involved in cytoskeletal dynamics, and proteins involved in regulating ion transport. Disruption of this protein's function has been implicated in tumorigenesis and metastasis. Mutations in this gene are associated with neurofibromatosis type II which is characterized by nervous system and skin tumors and ocular abnormalities. [provided by RefSeq, May 2022]

Primary Disease Associations & Inheritance

Meningioma, NF2-related, somaticMIM #607174
Schwannomatosis, somaticMIM #101000
Schwannomatosis, vestibularMIM #101000
AD
UniProtMesothelioma, malignant
560
ClinVar variants
76
Pathogenic / LP
1.00
pLI score· haploinsufficient
10
Active trials
Clinical Summary— NF2
🧬
Gene-Disease Validity (ClinGen)
neurofibromatosis type 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 329 VUS of 560 total submissions
💊
Clinical Trials
10 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.09LOEUF
pLI 1.000
Z-score 5.44
OE 0.00 (0.00–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.29Z-score
OE missense 0.64 (0.57–0.72)
208 obs / 323.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.57–0.72)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 0 / 34.5Missense obs/exp: 208 / 323.8Syn Z: 0.13

ClinVar Variant Classifications

560 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic16
VUS329
Likely Benign152
Conflicting3
60
Pathogenic
16
Likely Pathogenic
329
VUS
152
Likely Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
35
0
25
0
60
Likely Pathogenic
7
0
8
1
16
VUS
6
283
34
6
329
Likely Benign
0
3
53
96
152
Benign
0
0
0
0
0
Conflicting
—3
Total48286120103560

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NF2-related schwannomatosis

definitive
ADLoss Of FunctionAbsent Gene Product
EyeSkinCancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Meningioma, NF2-related, somatic

MIM #607174

Molecular basis of disorder known

Schwannomatosis, somatic

MIM #101000

Molecular basis of disorder known

Schwannomatosis, vestibular

MIM #101000

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — NF2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation.
Plotkin SR et al.·Genet Med
2022
Neurofibromatosis.
Korf BR·Handb Clin Neurol
2013Review
The neurofibromatoses.
Ferner RE·Pract Neurol
2010Review
[Neurofibromatoses].
Zimmer A·Radiologe
2013Review
Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma.
Laraba L et al.·Brain
2023
Targeted next-generation sequencing for differential diagnosis of neurofibromatosis type 2, schwannomatosis, and meningiomatosis.
Louvrier C et al.·Neuro Oncol
2018
Neurofibromatosis 2.
Baser ME et al.·Curr Opin Neurol
2003Review
Meningiomas and neurofibromatosis.
Goutagny S et al.·J Neurooncol
2010Review
Neurofibromatosis.
Gerber PA et al.·Eur J Med Res
2009Review
Update on Cancer and Central Nervous System Tumor Surveillance in Pediatric NF2-, SMARCB1-, and LZTR1-Related Schwannomatosis.
Perrino MR et al.·Clin Cancer Res
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Intracranial MeningiomaRecurrent MeningiomaNF2 Gene Mutation

Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas

RECRUITING
NCT02523014Phase PHASE2Alliance for Clinical Trials in OncologyStarted 2015-09-28
VismodegibFAK Inhibitor GSK2256098Capivasertib
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Acute LeukemiaAdenomatous PolyposisAdrenocortical Carcinoma

Familial Investigations of Childhood Cancer Predisposition

RECRUITING
NCT03050268St. Jude Children's Research HospitalStarted 2017-04-06
Refractory CancerCNS TumorsCNS Tumor, Adult

A Study of Avutometinib for People With Solid Tumor Cancers

RECRUITING
NCT06104488Phase PHASE1Memorial Sloan Kettering Cancer CenterStarted 2023-10-20
Avutometinib
Mesothelioma

New Preclinical and Clinical Approaches to Mesothelioma

RECRUITING
NCT06536179Marco Emilio BianchiStarted 2024-07-25
Advanced Solid TumorNSCLC (Non-small Cell Lung Cancer)Renal Cancer

A Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers

RECRUITING
NCT05873686Phase PHASE1Nuvectis Pharma, Inc.Started 2023-10-26
NXP900
Melanoma

MElanoma Research Lymph Node Prediction Implementation National_001

ACTIVE NOT RECRUITING
NCT04759781SkylineDxStarted 2021-08-25
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

RECRUITING
NCT03297606Phase PHASE2Canadian Cancer Trials GroupStarted 2018-03-23
OlaparibDasatinibNivolumab plus Ipilimumab
NF2 Deficiency

Gene Therapy for Neurofibromatosis Type 2 (NF2) with ST002

NOT YET RECRUITING
NCT06834438Phase NACancer Institute and Hospital, Chinese Academy of Medical SciencesStarted 2025-02-15
ST002

External Resources

Links to major genomics databases and tools