SYNE4: Spectrin Repeat Containing Nuclear Envelope Protein 4
A key component of the nuclear envelope involved in nuclear positioning and auditory function.
Gene Information Card
| Symbol | SYNE4 |
|---|---|
| Full Name | Spectrin Repeat Containing Nuclear Envelope Protein 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 163183 ncbi.nlm.nih.gov/gene/163183 |
| Ensembl ID | ENSG00000181381 |
| UniProt ID | Q8N205 |
| OMIM ID | 608429 |
| HGNC ID | 14587 |
| Aliases | Nesprin-4, C19orf46, FLJ20068 |
Description
SYNE4 encodes nesprin-4, a nuclear envelope protein that belongs to the spectrin repeat family. Nesprin-4 is a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, which connects the nuclear lamina to the cytoskeleton. It is essential for nuclear positioning and anchoring, particularly in auditory hair cells. Mutations in SYNE4 cause autosomal recessive deafness type 76 (DFNB76).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive deafness 76 (DFNB76) | Loss-of-function mutations disrupt nuclear positioning in cochlear hair cells, leading to progressive hearing loss. | ClinVar, OMIM |
| High-frequency hearing loss | SYNE4 mutations impair the LINC complex, causing mislocalization of nuclei in outer hair cells. | PubMed, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 5.2 | Low |
| Lung | 3.8 | Low |
| Kidney | 2.1 | Not detected |
| Cochlea (inner ear) | N/A | High (specific) - based on RNA-seq from GTEx and literature |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.5 | Low expression |
| K562 | 0.2 | Not detected |
| Hair cell lines (mouse) | N/A | High expression in outer hair cells (literature) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.135delC (p.Gln46Argfs*19) | Frameshift | Rare | Loss of function; associated with DFNB76 |
| c.487C>T (p.Arg163*) | Nonsense | Rare | Premature stop; loss of function |
| c.632G>A (p.Trp211*) | Nonsense | Rare | Loss of function; hearing loss |
Mutation functional classification
Loss of Function (LOF)
Most SYNE4 mutations are loss-of-function (nonsense, frameshift) leading to truncated nesprin-4 protein, disrupting nuclear envelope integrity in hair cells.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • nuclear envelope | • cytoskeleton |
| • nuclear migration | • actin binding |
| • spectrin binding | • nucleus |
Pathways
• LINC complex pathway
• Nuclear positioning
• Auditory mechanotransduction
Protein Summary
Nesprin-4 is a 60 kDa nuclear envelope protein with an N-terminal actin-binding domain and a C-terminal KASH domain that anchors it to the outer nuclear membrane. It interacts with SUN proteins to form the LINC complex, tethering the nucleus to the actin cytoskeleton. In cochlear hair cells, nesprin-4 is critical for proper nuclear positioning and cell survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SYNE4 Knockout HEK293 Cell Line | EDJ-KQ14799 | Human | 163183 | Details Get a Quote |
| SYNE4 Knockout HCT 116 Cell Line | EDJ-KQ46451 | Human | 163183 | Details Get a Quote |
| SYNE4 Knockout HeLa Cell Line | EDJ-KQ58855 | Human | 163183 | Details Get a Quote |
| SYNE4 Knockout A-549 Cell Line | EDJ-KQ67344 | Human | 163183 | Details Get a Quote |
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