SYNE1

Chr 6ARAD

spectrin repeat containing nuclear envelope protein 1

NCBI Gene: 23345 ENSG00000131018 UniProt: Q8NF91 OMIM: 608441

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. 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. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Arthrogryposis multiplex congenita 3, myogenic typeMIM #618484

Emery-Dreifuss muscular dystrophy 4, autosomal dominantMIM #612998

Spinocerebellar ataxia, autosomal recessive 8MIM #610743

Clinical highlights

Gene-disease validity (ClinGen)

arthrogryposis multiplex congenita 3, myogenic type · ARModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

LOF

Mechanism· G2P