NEXN (Nexilin F-Actin Binding Protein)
A key regulator of cardiac Z-disc integrity and sarcomere organization, implicated in dilated cardiomyopathy and related disorders.
Gene Information Card
| Symbol | NEXN |
|---|---|
| Full Name | Nexilin F-Actin Binding Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.1 |
| NCBI Gene ID | 91624 ncbi.nlm.nih.gov/gene/91624 |
| Ensembl ID | ENSG00000162614 |
| UniProt ID | Q0ZGT2 |
| OMIM ID | 613121 |
| HGNC ID | 29584 |
| Aliases | NEXN, nexilin, F-actin binding protein, CMH20, CMD1CC |
Description
NEXN encodes nexilin, an F-actin binding protein localized to the Z-disc of cardiac and skeletal muscle sarcomeres. It stabilizes the actin cytoskeleton and maintains sarcomere integrity. Mutations in NEXN are associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated Cardiomyopathy (DCM) | Disruption of Z-disc stability and actin binding leads to impaired sarcomere function and cardiac dilation. | ClinVar, OMIM #613121 |
| Hypertrophic Cardiomyopathy (HCM) | Missense mutations alter nexilin's actin-binding affinity, causing sarcomere disarray and hypertrophy. | ClinVar, OMIM #613121 |
| Left Ventricular Noncompaction (LVNC) | Loss of nexilin function may disrupt myocardial compaction during development. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 28.5 | High |
| Skeletal Muscle | 15.2 | Medium |
| Brain | 2.1 | Low |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (AC16) | 32.1 | High expression |
| Skeletal muscle myoblasts (HSMM) | 18.7 | Medium expression |
| HEK293 | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.154C>T (p.Arg52Trp) | Missense | Rare | Reduced actin binding; associated with DCM |
| c.437G>A (p.Arg146Gln) | Missense | Rare | Altered Z-disc localization; linked to HCM |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; severe DCM |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations reduce or abolish nexilin protein, leading to Z-disc instability and DCM.
Gain of Function (GOF)
Not reported for NEXN.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg52Trp) may produce a defective nexilin that interferes with wild-type protein at the Z-disc.
View complete mutation data：
Gene Ontology (GO)
| • actin binding (GO:0003779) | • cytoskeleton (GO:0005856) |
| • Z disc (GO:0030018) | • actin filament binding (GO:0051015) |
| • protein binding (GO:0005515) |
Pathways
• Cardiac muscle contraction (KEGG: hsa04260)
• Striated muscle contraction (Reactome: R-HSA-390522)
Protein Summary
Nexilin is a 1127-amino acid protein with an N-terminal actin-binding domain and a C-terminal coiled-coil region. It localizes to the Z-disc of cardiac and skeletal muscle sarcomeres, where it crosslinks actin filaments and anchors the sarcomere to the cell membrane. Post-translational modifications include phosphorylation at Ser-103, which modulates actin binding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEXN Knockout HEK293 Cell Line | EDJ-KQ10757 | Human | 91624 | Details Get a Quote |
| NEXN Knockout A-549 Cell Line | EDJ-KQ38359 | Human | 91624 | Details Get a Quote |
| NEXN Knockout HeLa Cell Line | EDJ-KQ38360 | Human | 91624 | Details Get a Quote |
| NEXN Knockout HCT 116 Cell Line | EDJ-KQ74726 | Human | 91624 | Details Get a Quote |
