NF2 (Neurofibromin 2) Gene: Merlin Tumor Suppressor
Comprehensive guide to the NF2 gene, its function, associated diseases, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | NF2 |
|---|---|
| Full Name | Neurofibromin 2 (merlin) |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 4771 ncbi.nlm.nih.gov/gene/4771 |
| Ensembl ID | ENSG00000186575 |
| UniProt ID | P35240 |
| OMIM ID | 607379 |
| HGNC ID | 7773 |
| Aliases | SCH, BANF, merlin, moesin-ezrin-radixin-like protein |
Description
The NF2 gene encodes merlin (moesin-ezrin-radixin-like protein), a tumor suppressor that links the actin cytoskeleton to cell membrane proteins. Merlin regulates cell proliferation, adhesion, and survival, and its loss leads to tumor formation, particularly in the nervous system.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurofibromatosis type 2 (NF2) | Biallelic inactivation of NF2 leads to loss of merlin function, causing schwannomas, meningiomas, and ependymomas. | OMIM, ClinVar |
| Schwannomatosis | Somatic mutations in NF2 are found in schwannomas, though germline mutations are rare; mosaic mutations contribute. | COSMIC, ClinVar |
| Meningioma | NF2 mutations are the most common genetic alteration in sporadic meningiomas, leading to merlin loss. | COSMIC, ClinVar |
| Malignant mesothelioma | NF2 inactivation is frequent in mesothelioma, contributing to tumor progression. | COSMIC, ClinVar |
| Breast cancer | Loss of NF2 expression has been observed in some breast cancers, associated with aggressive features. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Nerve | 8.2 | Low |
| Lung | 6.1 | Low |
| Kidney | 5.4 | Low |
| Testis | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression |
| HeLa | 10.2 | Moderate |
| A549 | 7.8 | Low |
| MCF7 | 6.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.592C>T (p.Arg198*) | Nonsense | ~5% of NF2 patients | Truncated protein, loss of function |
| c.1021C>T (p.Arg341*) | Nonsense | ~3% | Loss of function |
| c.169C>T (p.Arg57*) | Nonsense | ~2% | Loss of function |
| c.784C>T (p.Arg262*) | Nonsense | ~2% | Loss of function |
| c.1340T>C (p.Leu447Pro) | Missense | Rare | Disrupts protein folding, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most NF2 mutations are loss-of-function, leading to merlin inactivation and tumor suppressor pathway disruption.
Gain of Function (GOF)
No gain-of-function mutations are reported; NF2 acts as a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type merlin function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • actin binding | • cytoskeletal protein binding |
| • protein kinase binding | • cell adhesion molecule binding |
| • identical protein binding | • protein domain specific binding |
| • cell junction | • cytoplasm |
| • cytoskeleton | • membrane |
| • nucleus | • cell proliferation |
| • negative regulation of cell growth | • negative regulation of cell migration |
| • signal transduction | • hippo signaling |
Pathways
• Hippo signaling pathway
• Cell adhesion and cytoskeleton remodeling
• PI3K/AKT signaling (regulation)
• RTK signaling (regulation)
Protein Summary
Merlin is a 595-amino acid protein with a FERM domain, a central alpha-helical region, and a C-terminal domain. It localizes to the plasma membrane and links membrane proteins to the actin cytoskeleton. Merlin regulates contact inhibition, cell proliferation, and survival by modulating multiple signaling pathways, including Hippo/YAP, mTOR, and Rac/Pak. Loss of merlin leads to uncontrolled cell growth and tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NF2 Knockout HEK293 Cell Line | EDJ-KQ1363 | Human | 4771 | Details Get a Quote |
| NF2 Knockout HCT 116 Cell Line | EDJ-KQ19508 | Human | 4771 | Details Get a Quote |
| NF2 Knockout A-549 Cell Line | EDJ-KQ20854 | Human | 4771 | Details Get a Quote |
| NF2 Knockout HeLa Cell Line | EDJ-KQ20856 | Human | 4771 | Details Get a Quote |
