EPM2A

Chr 6AR

EPM2A glucan phosphatase, laforin

Also known as: EPM2, MELF, MELF2

This gene encodes a dual-specificity phosphatase and may be involved in the regulation of glycogen metabolism. The protein acts on complex carbohydrates to prevent glycogen hyperphosphorylation, thus avoiding the formation of insoluble aggregates. Loss-of-function mutations in this gene have been associated with Lafora disease, a rare, adult-onset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of insoluble particles called Lafora bodies, which are derived from glycogen. [provided by RefSeq, Jan 2018]

OMIMResearchGenerating clinical summary…
GOFmechanismARLOEUF 1.341 OMIM phenotype
Clinical SummaryEPM2A
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Gene-Disease Validity (ClinGen)
Lafora disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.34LOEUF
pLI 0.000
Z-score 0.73
OE 0.77 (0.461.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.26Z-score
OE missense 1.06 (0.931.20)
165 obs / 155.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.77 (0.461.34)
00.351.4
Missense OE?1.06 (0.931.20)
00.61.4
Synonymous OE?1.27
01.21.6
LoF obs/exp: 9 / 11.7Missense obs/exp: 165 / 155.9Syn Z: -1.64

This gene — mechanism propensity

DN
0.6066th %ile
GOF
0.6931th %ile
LOF
0.53top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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.

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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