EPM2A
Chr 6AREPM2A glucan phosphatase, laforin
Also known as: EPM2, MELF, MELF2
The protein is a dual-specificity phosphatase that prevents glycogen hyperphosphorylation by acting on complex carbohydrates, thereby avoiding formation of insoluble glycogen aggregates. Mutations cause Lafora disease (myoclonic epilepsy of Lafora type 1), a rare neurodegenerative disorder with adult onset characterized by myoclonus epilepsy and accumulation of insoluble glycogen-derived particles called Lafora bodies. Inheritance is autosomal recessive.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function 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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 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 | 21 | 1 | 8 | 0 | 30 |
Likely Pathogenic | 9 | 8 | 1 | 0 | 18 |
VUS | 4 | 178 | 8 | 0 | 190 |
Likely Benign | 2 | 14 | 36 | 86 | 138 |
Benign | 0 | 0 | 14 | 0 | 14 |
Conflicting | — | 7 | |||
| Total | 36 | 201 | 67 | 86 | 397 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
EPM2A · 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