EPM2A

Chr 6

EPM2A glucan phosphatase, laforin

Also known as: EPM2, MELF, MELF2

NCBI Gene: 7957ENSG00000112425UniProt: B3EWF7

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]

510
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EPM2A
🧬
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.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 230 VUS of 510 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.34LOEUF
pLI 0.000
Z-score 0.73
OE 0.77 (0.46–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.26Z-score
OE missense 1.06 (0.93–1.20)
165 obs / 155.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.77 (0.46–1.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.93–1.20)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.27
0≤1.21.6
LoF obs/exp: 9 / 11.7Missense obs/exp: 165 / 155.9Syn Z: -1.64

ClinVar Variant Classifications

510 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic29
VUS230
Likely Benign168
Benign19
Conflicting20
44
Pathogenic
29
Likely Pathogenic
230
VUS
168
Likely Benign
19
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
2
25
0
44
Likely Pathogenic
8
14
7
0
29
VUS
5
211
14
0
230
Likely Benign
1
26
41
100
168
Benign
0
2
15
2
19
Conflicting
—20
Total31255102102510

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.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — EPM2A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lafora disease.
Turnbull J et al.·Epileptic Disord
2016Review
Polyglucosan storage myopathies.
Hedberg-Oldfors C et al.·Mol Aspects Med
2015Review
[Lafora's disease (EPM2)].
Genton P·Rev Neurol (Paris)
2007Review
PDE7B, NMBR and EPM2A Variants and Schizophrenia: A Case-Control and Pharmacogenetics Study.
Porcelli S et al.·Neuropsychobiology
2016
Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes.
Singh S et al.·Hum Mutat
2009Review
Lafora disease - from pathogenesis to treatment strategies.
Nitschke F et al.·Nat Rev Neurol
2018Review
Lafora disease: from genotype to phenotype.
Parihar R et al.·J Genet
2018Review
[Lafora disease: a review of the literature].
Desdentado L et al.·Rev Neurol
2019Review
Prognostic value of pathogenic variants in Lafora Disease: systematic review and meta-analysis of patient-level data.
Pondrelli F et al.·Orphanet J Rare Dis
2023Meta-analysis
Clinical implications and molecular mechanism of long noncoding RNA LINC00518 and protein-coding genes in skin cutaneous melanoma by genome‑wide investigation.
Wang S et al.·Arch Dermatol Res
2025Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools