PLEC
Chr 8ARADplectin
Also known as: EBS1, EBS5A, EBS5B, EBS5C, EBS5D, EBSMD, EBSND, EBSO
Plectin interlinks intermediate filaments with microtubules and microfilaments, anchors intermediate filaments to desmosomes and hemidesmosomes, and serves as a structural component of muscle. Mutations cause epidermolysis bullosa simplex with various presentations (including muscular dystrophy, pyloric atresia, and Ogna type) and limb-girdle muscular dystrophy, inherited in autosomal recessive or autosomal dominant patterns. The gene is highly constrained against loss-of-function mutations, reflecting its essential role in maintaining skin and muscle tissue integrity.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PLEC · 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