SYNE2: Spectrin Repeat Containing Nuclear Envelope Protein 2
Key player in nuclear positioning and cytoskeletal organization, linked to Emery-Dreifuss muscular dystrophy and dilated cardiomyopathy.
Gene Information Card
| Symbol | SYNE2 |
|---|---|
| Full Name | Spectrin Repeat Containing Nuclear Envelope Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q23.2 |
| NCBI Gene ID | 23224 ncbi.nlm.nih.gov/gene/23224 |
| Ensembl ID | ENSG00000154678 |
| UniProt ID | Q8WXH0 |
| OMIM ID | 608442 |
| HGNC ID | 17084 |
| Aliases | NUANCE, Nesp2, Nesprin-2, SYNE-2, C14orf49 |
Description
The SYNE2 gene encodes nesprin-2, a large spectrin-repeat protein that anchors the nucleus to the cytoskeleton. It is a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex, essential for nuclear positioning, cell migration, and mechanical stability. Mutations in SYNE2 cause autosomal dominant Emery-Dreifuss muscular dystrophy 5 (EDMD5) and dilated cardiomyopathy 1G (CMD1G).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Emery-Dreifuss muscular dystrophy 5 (EDMD5) | Disruption of nuclear-cytoskeletal coupling leads to nuclear instability and muscle cell death | ClinVar, OMIM |
| Dilated cardiomyopathy 1G (CMD1G) | Impaired nuclear anchorage in cardiomyocytes causes contractile dysfunction and dilation | ClinVar, OMIM |
| Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Altered nuclear positioning and mechanical stress response in cardiac cells | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 28.5 | High |
| Heart | 22.1 | High |
| Lung | 12.3 | Medium |
| Brain | 8.7 | Medium |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung) | 15.6 | High expression |
| HeLa (cervical) | 10.2 | Medium expression |
| HepG2 (liver) | 5.8 | Low expression |
| K562 (blood) | 3.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1574C>T (p.Thr525Met) | Missense | Rare | Alters spectrin repeat domain, disrupts LINC complex binding |
| c.2083G>A (p.Glu695Lys) | Missense | Rare | Impaired nuclear positioning in muscle cells |
| c.1225_1227del (p.Lys409del) | Deletion | Rare | Loss of function, associated with EDMD5 |
Mutation functional classification
Loss of Function (LOF)
Deletions and truncating mutations reduce nesprin-2 expression, weakening nuclear-cytoskeletal linkage.
Gain of Function (GOF)
Not reported for SYNE2.
Dominant Negative (DN)
Missense mutations in the spectrin repeat region can interfere with wild-type nesprin-2 function, causing dominant disease.
View complete mutation data：
Gene Ontology (GO)
| • nuclear envelope | • cytoskeleton |
| • nuclear migration | • actin binding |
| • microtubule binding | • nucleus organization |
Pathways
• LINC complex pathway
• Nuclear positioning pathway
• Cytoskeletal signaling
Protein Summary
Nesprin-2 is a giant protein (∼796 kDa) containing an N-terminal actin-binding domain, a central spectrin repeat rod domain, and a C-terminal KASH domain that anchors it to the nuclear envelope. It interacts with SUN proteins to form the LINC complex, connecting the nucleus to the actin and microtubule cytoskeletons. This enables nuclear movement, positioning, and mechanotransduction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SYNE2 Knockout HEK293 Cell Line | EDJ-KQ2600 | Human | 23224 | Details Get a Quote |
| SYNE2 Knockout A-549 Cell Line | EDJ-KQ23305 | Human | 23224 | Details Get a Quote |
| SYNE2 Knockout HCT 116 Cell Line | EDJ-KQ23306 | Human | 23224 | Details Get a Quote |
| SYNE2 Knockout HeLa Cell Line | EDJ-KQ23307 | Human | 23224 | Details Get a Quote |
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