SYNE1
Chr 6ARADspectrin repeat containing nuclear envelope protein 1
Also known as: 8B, AMC3, AMCM, ARCA1, C6orf98, CPG2, EDMD4, KASH1
This gene encodes a spectrin repeat protein that localizes to the nuclear outer membrane in skeletal muscle, smooth muscle, and lymphocytes. Mutations cause autosomal recessive spinocerebellar ataxia 8 (cerebellar ataxia type 1), arthrogryposis multiplex congenita type 3, and autosomal dominant Emery-Dreifuss muscular dystrophy type 4. The predicted mechanism involves gain-of-function effects from mutations affecting this nuclear membrane protein.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
700 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 16 | 0 | 7 | 0 | 23 |
Likely Pathogenic | 9 | 1 | 0 | 0 | 10 |
VUS | 3 | 276 | 21 | 13 | 313 |
Likely Benign | 0 | 14 | 62 | 109 | 185 |
Benign | 0 | 24 | 3 | 20 | 47 |
Conflicting | — | 56 | |||
| Total | 28 | 315 | 93 | 142 | 634 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SYNE1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools