SUN1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the SUN1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | SUN1 |
|---|---|
| Full Name | Sad1 and UNC84 domain containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p22.3 |
| NCBI Gene ID | 23353 ncbi.nlm.nih.gov/gene/23353 |
| Ensembl ID | ENSG00000128594 |
| UniProt ID | O94901 |
| OMIM ID | 607723 |
| HGNC ID | 18587 |
| Aliases | KIAA0810, UNC84A |
Description
The SUN1 gene encodes a type II membrane protein localized to the inner nuclear membrane. It is a core component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, which connects the nuclear lamina to the cytoskeleton. SUN1 interacts with nesprin proteins in the perinuclear space and with A-type lamins in the nucleoplasm, playing a critical role in nuclear positioning, mechanical stability, and cellular signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Emery-Dreifuss Muscular Dystrophy (EDMD) | Mutations in SUN1 are implicated in EDMD, likely by disrupting the LINC complex and nuclear-cytoskeletal coupling, leading to nuclear fragility and muscle cell death. | ClinVar, OMIM |
| Dilated Cardiomyopathy (DCM) | SUN1 variants may contribute to DCM by impairing nuclear mechanics in cardiomyocytes, affecting gene expression and cellular response to mechanical stress. | ClinVar, OMIM |
| Limb-Girdle Muscular Dystrophy (LGMD) | Similar to EDMD, SUN1 mutations can cause LGMD phenotypes by disrupting the nuclear envelope structure and function in skeletal muscle. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Testis | 25.4 | Medium |
| Skeletal Muscle | 18.7 | Medium |
| Heart | 15.2 | Medium |
| Kidney | 12.1 | Low |
| Liver | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| A549 (Lung) | 15.3 | Moderate expression |
| MCF7 (Breast) | 12.8 | Moderate expression |
| HeLa (Cervical) | 10.2 | Low expression |
| HepG2 (Liver) | 7.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.157C>T (p.Arg53Cys) | Missense | Rare | Disrupts SUN domain interaction with nesprins, affecting LINC complex integrity. |
| c.224G>A (p.Arg75His) | Missense | Rare | Alters protein stability and nuclear envelope localization. |
| c.345delA (p.Lys115fs) | Frameshift | Very rare | Leads to premature truncation and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SUN1, such as frameshift or nonsense variants, lead to a truncated or absent protein, disrupting the LINC complex and nuclear-cytoskeletal coupling. This can result in nuclear deformation and increased susceptibility to mechanical stress, contributing to muscular dystrophy phenotypes.
Gain of Function (GOF)
No clear gain-of-function mutations have been described for SUN1. Most pathogenic variants are associated with loss of function or dominant-negative effects.
Dominant Negative (DN)
Missense mutations in the SUN domain can act in a dominant-negative manner. The mutant protein may still localize to the inner nuclear membrane but fail to interact properly with nesprins or lamins, disrupting the function of the wild-type protein and the entire LINC complex.
View complete mutation data：
Gene Ontology (GO)
| • nuclear envelope organization | • nuclear migration |
| • cytoskeleton organization | • protein localization to nucleus |
| • meiotic nuclear division | • telomere maintenance |
| • nuclear membrane fusion |
Pathways
• LINC complex pathway
• Nuclear envelope breakdown and reassembly
• Meiotic telomere attachment
Protein Summary
SUN1 is a 812-amino acid protein with a molecular weight of approximately 90 kDa. It contains an N-terminal nucleoplasmic domain, a transmembrane domain, and a C-terminal SUN domain located in the perinuclear space. The SUN domain interacts with the KASH domain of nesprin proteins, forming the core of the LINC complex. This complex spans the nuclear envelope, connecting the nuclear lamina to the actin cytoskeleton, microtubules, and intermediate filaments. SUN1 is essential for proper nuclear positioning, cell migration, and mechanotransduction. It also plays a role in meiotic chromosome dynamics by anchoring telomeres to the nuclear envelope.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SUN1 Knockout HEK293 Cell Line | EDJ-KQ7984 | Human | 23353 | Details Get a Quote |
| SUN1 Knockout A-549 Cell Line | EDJ-KQ33699 | Human | 23353 | Details Get a Quote |
| SUN1 Knockout HCT 116 Cell Line | EDJ-KQ33700 | Human | 23353 | Details Get a Quote |
| SUN1 Knockout HeLa Cell Line | EDJ-KQ33701 | Human | 23353 | Details Get a Quote |
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