NF2

Chr 22AD

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

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

The protein regulates contact-dependent inhibition of cell proliferation and functions in cell-cell adhesion and transmembrane signaling by linking cytoskeletal components with cell membrane proteins. Mutations cause neurofibromatosis type II, an autosomal dominant disorder characterized by nervous system and skin tumors and ocular abnormalities, as well as schwannomatosis and meningiomas. The pathogenic mechanism involves disruption of the protein's tumor suppressor function, leading to loss of growth control and subsequent tumorigenesis.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.093 OMIM phenotypes
VCEP Guidelines: NeurofibromatosesIn Progress
ClinGen Panel
Clinical SummaryNF2
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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.
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Clinical Trials
10 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 5.44
OE 0.00 (0.000.09)
Highly constrained

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

Missense Constraint
2.29Z-score
OE missense 0.64 (0.570.72)
208 obs / 323.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.09)
00.351.4
Missense OE0.64 (0.570.72)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 0 / 34.5Missense obs/exp: 208 / 323.8Syn Z: 0.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNF2-related schwannomatosisLOFAD
DN
0.4884th %ile
GOF
0.5366th %ile
LOF
0.60top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation · LOEUF 0.09

Literature Evidence

LOFRole of NF2 haploinsufficiency in NF2-associated polyneuropathy.PMID:17655741

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
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
Acute LeukemiaAdenomatous PolyposisAdrenocortical Carcinoma

Familial Investigations of Childhood Cancer Predisposition

RECRUITING
NCT03050268St. Jude Children's Research HospitalStarted 2017-04-06
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
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
Mesothelioma

New Preclinical and Clinical Approaches to Mesothelioma

RECRUITING
NCT06536179Marco Emilio BianchiStarted 2024-07-25
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
Melanoma

MElanoma Research Lymph Node Prediction Implementation National_001

ACTIVE NOT RECRUITING
NCT04759781SkylineDxStarted 2021-08-25
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗