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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SUN1
Sad1 and UNC84 domain containing 1
Chromosome 7 · 7p22.3
NCBI Gene: 23353Ensembl: ENSG00000164828.18HGNC: HGNC:18587UniProt: A0A146IHP0
112PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
meiotic nuclear membrane microtubule tethering complexprotein bindingidentical protein bindingnuclear matrix anchoring at nuclear membraneatrial fibrillationneurodegenerative diseaseAbnormality of the skeletal systematrial flutter
✦AI Summary

SUN1 (Sad1 and UNC84 domain containing 1) is a nuclear envelope protein that serves as a critical component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, connecting nuclear and cytoplasmic mechanical forces 1. The protein functions as a mechano-regulator that controls nuclear size, stiffness, and chr7 accessibility in response to cellular cues 2. SUN1 modulates gene expression through nuclear remodeling, as demonstrated in macrophage M1 polarization where LPS treatment decreases SUN1/2 levels to shrink and soften the nucleus, altering chr7 accessibility 2. The protein also regulates stem cell differentiation, with SUN1 downregulation promoting osteogenesis while inhibiting adipogenesis through effects on α-tubulin and CD36 expression 3. Disease relevance includes mutations causing Emery-Dreifuss muscular dystrophy 4 and a common variant (H118Y) associating with hepatic steatosis and metabolic disorders 5. In cardiomyopathy, SUN1 disruption prevents progression of lamin-induced cardiac failure by displacing KASH complexes from the nuclear periphery 1. Additionally, SUN1 splicing variants differentially regulate nucleolar structure and chr7 modifications 6, while cytoskeletal stiffness regulation involves SUN1/2 interaction with RhoA in cellular senescence pathways 7.

Sources cited
1
SUN1 is a LINC complex component and its disruption prevents lamin-induced cardiomyopathy progression
PMID: 34354059
2
SUN1/2 act as mechano-regulators controlling nuclear size, stiffness, and chromatin accessibility during macrophage M1 polarization
PMID: 37828059
3
SUN1 regulates stem cell differentiation by modulating osteogenesis and adipogenesis through α-tubulin and CD36 expression
PMID: 39383106
4
SUN1 mutations are associated with Emery-Dreifuss muscular dystrophy
PMID: 31840275
5
Common SUN1 H118Y variant associates with hepatic steatosis and metabolic traits
PMID: 37567366
6
SUN1 splicing variants SUN1_888 and SUN1_916 differentially regulate nucleolar structure
PMID: 32931086
7
SUN1/2 interact with RhoA in regulating cytoskeletal stiffness and cellular senescence in progeria
PMID: 32710480
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.51Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
Abnormality of the skeletal systemOpen Targets
0.39Weak
atrial flutterOpen Targets
0.37Weak
heart diseaseOpen Targets
0.31Weak
cardiac arrhythmiaOpen Targets
0.30Weak
infectious meningitisOpen Targets
0.27Weak
retinopathyOpen Targets
0.27Weak
Loss of consciousnessOpen Targets
0.23Weak
Emery-Dreifuss muscular dystrophyOpen Targets
0.21Weak
azoospermiaOpen Targets
0.10Suggestive
HIV-1 infectionOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
cancerOpen Targets
0.07Suggestive
acute lymphoblastic leukemiaOpen Targets
0.07Suggestive
spinocerebellar ataxia type 32Open Targets
0.07Suggestive
spermatogenic failure 57Open Targets
0.07Suggestive
spermatogenic failure 50Open Targets
0.07Suggestive
Spinocerebellar ataxia type 41Open Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LMNB2Protein interaction100%SPDYAProtein interaction100%TERB2Protein interaction100%TERB1Protein interaction99%SYNE4Protein interaction99%EMDProtein interaction98%
Tissue Expression6 tissues
Ovary
100%
Heart
91%
Lung
50%
Brain
38%
Liver
36%
Bone Marrow
19%
Gene Interaction Network
Click a node to explore
SUN1LMNB2SPDYATERB2TERB1SYNE4EMD
PROTEIN STRUCTURE
Preparing viewer…
PDB6R2I · 1.54 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.46–0.71]
RankingsWhere SUN1 stands among ~20K protein-coding genes
  • #4,250of 20,598
    Most Researched112 · top quartile
  • #5,466of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedSUN1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Emery-Dreifuss muscular dystrophy.
PMID: 31840275
Muscle Nerve · 2020
1.00
2
SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness.
PMID: 37828059
Nat Commun · 2023
0.90
3
Lamin A/C deficiency-mediated ROS elevation contributes to pathogenic phenotypes of dilated cardiomyopathy in iPSC model.
PMID: 39143095
Nat Commun · 2024
0.80
4
SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating α-tubulin and CD36 expression.
PMID: 39383106
J Cell Mol Med · 2024
0.70
5
Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy.
PMID: 34354059
Nat Commun · 2021
0.60