SYNE1: Spectrin Repeat Containing Nuclear Envelope Protein 1
Key player in nuclear positioning and neuromuscular junction integrity; mutations linked to autosomal recessive spinocerebellar ataxia and Emery-Dreifuss muscular dystrophy.
Gene Information Card
| Symbol | SYNE1 |
|---|---|
| Full Name | spectrin repeat containing nuclear envelope protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 6q25.2 |
| NCBI Gene ID | 23345 ncbi.nlm.nih.gov/gene/23345 |
| Ensembl ID | ENSG00000131018 |
| UniProt ID | Q8NF91 |
| OMIM ID | 608441 |
| HGNC ID | 17089 |
| Aliases | CPG2, MYNE1, Nesp1, SCAR8, dJ45H2.3, nesprin-1, enaptin |
Description
SYNE1 encodes nesprin-1, a giant spectrin-repeat protein that anchors the nucleus to the cytoskeleton via the LINC complex. It is essential for nuclear positioning, mechanotransduction, and maintaining neuromuscular junction integrity. Mutations cause autosomal recessive spinocerebellar ataxia type 8 (SCAR8) and autosomal dominant Emery-Dreifuss muscular dystrophy type 4 (EDMD4).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive spinocerebellar ataxia type 8 (SCAR8) | Loss-of-function mutations disrupt nuclear-cytoskeletal coupling in Purkinje cells, leading to cerebellar degeneration. | ClinVar, OMIM #610743 |
| Emery-Dreifuss muscular dystrophy type 4 (EDMD4) | Dominant mutations impair nuclear envelope integrity and nuclear positioning in skeletal and cardiac muscle. | ClinVar, OMIM #612998 |
| Arthrogryposis multiplex congenita | Biallelic truncating variants cause severe congenital contractures due to defective nuclear anchorage in motor neurons. | ClinVar, OMIM #618484 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 32.5 | High |
| Cerebellum | 28.1 | High |
| Heart | 22.3 | Medium |
| Testis | 18.7 | Medium |
| Lung | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.0 | High expression; used in neuronal studies |
| HeLa (cervical carcinoma) | 12.3 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 8.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.12535C>T (p.Arg4179*) | Nonsense | Rare | Loss-of-function; truncates nesprin-1, causing SCAR8 |
| c.15782G>A (p.Arg5261His) | Missense | Rare | Dominant-negative effect in EDMD4; disrupts SUN domain binding |
| c.20746C>T (p.Arg6916*) | Nonsense | Rare | Loss-of-function; associated with arthrogryposis |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated nesprin-1; cause SCAR8 and arthrogryposis.
Gain of Function (GOF)
Not reported for SYNE1.
Dominant Negative (DN)
Missense mutations in the C-terminal KASH domain (e.g., p.Arg5261His) disrupt LINC complex assembly, causing EDMD4.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005637 nuclear envelope | • GO:0005856 cytoskeleton |
| • GO:0006996 organelle organization | • GO:0030054 cell junction |
| • GO:0051015 actin filament binding | • GO:0008092 cytoskeletal protein binding |
| • GO:0042383 sarcolemma | • GO:0007010 cytoskeleton organization |
Pathways
• LINC complex pathway (R-HSA-9634638)
• Nuclear envelope breakdown and reassembly (R-HSA-2980767)
• Muscle contraction (R-HSA-397014)
Protein Summary
Nesprin-1 (SYNE1) is a giant nuclear envelope protein with an N-terminal actin-binding domain, a central spectrin-repeat rod, and a C-terminal KASH domain that anchors it to the inner nuclear membrane. It forms the LINC complex with SUN proteins, connecting the nucleoskeleton to the cytoskeleton. This linkage is critical for nuclear positioning, cell migration, and mechanotransduction, especially in neurons and muscle cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SYNE1 Knockout HEK293 Cell Line | EDJ-KQ3357 | Human | 23345 | Details Get a Quote |
| SYNE1 Knockout A-549 Cell Line | EDJ-KQ25019 | Human | 23345 | Details Get a Quote |
| SYNE1 Knockout HCT 116 Cell Line | EDJ-KQ25020 | Human | 23345 | Details Get a Quote |
| SYNE1 Knockout HeLa Cell Line | EDJ-KQ25021 | Human | 23345 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
