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SYNE4
spectrin repeat containing nuclear envelope family member 4
SYNE4 is located on the long (q) arm of chromosome 19, at band 19q13.12. Arm ratio per GRCh38 - banding schematic.
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Overview
SYNE4 (spectrin repeat containing nuclear envelope family member 4) is a gene located on chromosome 19 that encodes a member of the nesprin protein family. Nesprins are a group of proteins embedded in the nuclear envelope, the double-membrane structure that surrounds the genetic material within the nucleus of cells.
The SYNE4 protein is thought to contribute to the mechanical stability and spatial organisation of the nucleus, although detailed functional studies remain limited compared to other members of the nesprin family. Understanding SYNE4's role may provide insights into how cells maintain nuclear architecture and respond to mechanical stresses.
What the gene does
The SYNE4 protein is believed to participate in anchoring the nucleus within the cell and maintaining its structural integrity. Members of the nesprin family typically form connections between the nuclear envelope and the cytoskeleton, the network of protein filaments that provides structural support throughout the cell.
These protein linkages are thought to enable the nucleus to withstand mechanical forces and maintain its position within the cell. The spectrin repeat motifs that characterise nesprin family members generally contribute to protein flexibility and allow for protein-protein interactions. Research suggests that nuclear envelope proteins play important roles in various cellular processes, including gene regulation and cell division, although the specific contributions of SYNE4 to these processes have not been fully characterised.
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Chromosome location
SYNE4 is located on the long arm of chromosome 19 at position 19q13.12. This chromosomal region contains numerous genes involved in diverse biological processes. The precise number of exons and the complete genomic structure of SYNE4 have not been extensively documented in current genomic databases, reflecting the ongoing characterisation of this gene.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. Current structural annotations indicate that SYNE4 contains spectrin repeat motifs, which are typically elongated structures that provide flexibility and mediate interactions with other proteins. The overall organisation of functional domains within the SYNE4 protein awaits further biochemical and structural investigation.
Key variants
Genetic variants in SYNE4 have been catalogued in population databases and clinical variant repositories. The functional impact of most SYNE4 variants remains uncertain, as large-scale genotype-phenotype studies for this gene are limited. As with other genes, variants may range from benign polymorphisms that do not affect protein function to potentially pathogenic changes that could disrupt normal cellular processes.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.121_122dup | p.Ser41fs | Pathogenic/Likely pathogenic | ★★☆☆ | SYNE4-related disorder |
c.129-1G>T | - | Pathogenic | ★★☆☆ | not provided |
c.253_259dup | p.Ala87fs | Pathogenic/Likely pathogenic | ★★☆☆ | SYNE4-related disorder |
c.336C>A | p.Cys112Ter | Pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 76 |
c.442C>T | p.Arg148Ter | Pathogenic/Likely pathogenic | ★★☆☆ | SYNE4-related disorder |
c.662_666del | p.Glu221fs | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 76 |
c.702del | p.Trp236fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.889C>T | p.Arg297Ter | Pathogenic | ★★☆☆ | Nonsyndromic genetic hearing loss |
c.96dup | p.Val33fs | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 76 |
c.972+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 76 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Currently, no specific inherited conditions have been definitively linked to pathogenic variants in SYNE4 in major clinical genetics databases. The gene is not included in routine clinical genetic screening panels for known hereditary disorders. As research into nuclear envelope biology continues, future studies may clarify whether SYNE4 variants contribute to disease phenotypes.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the SYNE4 gene do?
SYNE4 encodes a protein that is part of the nuclear envelope, the membrane system surrounding the cell nucleus. The protein is thought to help maintain the structural framework and positioning of the nucleus within cells, though its precise biological role is still being investigated.
Are there any conditions associated with SYNE4?
Currently, no specific inherited conditions have been definitively linked to pathogenic variants in SYNE4. The gene is not included in routine clinical genetic testing panels for known hereditary disorders at this time.
How does SYNE4 relate to other nesprin family genes?
SYNE4 is a member of the spectrin repeat-containing nuclear envelope family, which includes SYNE1, SYNE2, and SYNE3. These related genes encode proteins that perform similar structural roles at the nuclear envelope, connecting the nucleus to the cell's internal scaffolding.