SYNE3
protein-codingspectrin repeat containing nuclear envelope family member 3, the group of KASH domain containing|Spectrin repeat containing nuclear envelope family
Gene summary
Enables actin filament binding activity and cytoskeleton-nuclear membrane anchor activity. Involved in cytoskeleton organization; establishment of protein localization to membrane; and regulation of cell shape. Located in nuclear membrane. Part of meiotic nuclear membrane microtubule tethering complex. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Jul 2025]
- C14orf49
- LINC00341
- C14orf139
- NCRNA00341
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~109.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SYNE3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152592.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 189 | 13 | 202 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 190 | 14 | 0 | 204 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689805.3 | 17 | MANE Select | |
| Ensembl | ENSP00000507501.1 | 17 | MANE Select | |
| RefSeq | NP_001350621.1 | 17 | Standard | |
| RefSeq | NP_001371210.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| syne3 | Danio rerio | Structure: epidermal cell Quality: spatial pattern abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cytoskeleton organization
- nuclear migration
- regulation of cell shape
- nucleus localization
- establishment of protein localization to membrane
Molecular Function
- protein binding
- actin filament binding
Cellular Component
- nuclear envelope
- nuclear outer membrane
- cytoplasm
- rough endoplasmic reticulum
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334258
- Coding exons
- 17
- Length
- 58343
- Individuals with no LoFs
- 125531
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 217
- Defined
- 125748
- p
- 0.000863
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00387 | 577 | 577 | 1.00 | 0.0000366 | 6283 |
| Missense (PolyPhen) | 119 | 108.82 | 1.0936 | 1402 | ||
| Synonymous | -0.767 | 274 | 258 | 1.06 | 0.0000167 | 1983 |
| Loss of Function | 1.08 | 43 | 51.4 | 0.837 | 0.00000254 | 530 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0011 | notable |
| Latino/Admixed American | 0.0018 | 0.0018 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0035 | 0.0035 | notable |
| Finnish | 0.000095 | 0.000092 | rare |
| European (Non-Finnish) | 0.00036 | 0.00035 | rare |
| South Asian | 0.00082 | 0.00082 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Probable anchoring protein which tethers the nucleus to the cytoskeleton by binding PLEC which can associate with the intermediate filament system. Plays a role in the regulation of aortic epithelial cell morphology, and is required for flow-induced centrosome polarization and directional migration in aortic endothelial cells. {ECO:0000269|PubMed:16330710, ECO:0000269|PubMed:18396275, ECO:0000269|PubMed:21937718}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- RVIS EVS
- 1.17
- RVIS percentile EVS
- 92.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | High | Medium | High |