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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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EPM2A
EPM2A glucan phosphatase, laforin
Chromosome 6 Β· 6q24.3
NCBI Gene: 7957Ensembl: ENSG00000112425.16HGNC: HGNC:3413UniProt: O95278
99PubMed Papers
21Diseases
0Drugs
56Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of macroautophagynegative regulation of TOR signalingprotein bindingnucleusmyoclonic epilepsy of Lafora 1Lafora diseaseProgressive myoclonic epilepsygenetic disorder
✦AI Summary

EPM2A encodes laforin, a glucan phosphatase that regulates glycogen metabolism and structure. Laforin functions as part of a protein complex with malin to control glycogen synthesis and prevent accumulation of abnormal glycogen 1. The enzyme dephosphorylates glycogen, maintaining proper glucose polymer architecture and preventing the formation of toxic polyglucosans 2. Laforin also negatively regulates mTOR signaling and promotes macroautophagy, contributing to protein quality control via the ubiquitin-proteasome system 3. EPM2A mutations cause Lafora disease, an autosomal recessive progressive myoclonus epilepsy characterized by accumulation of abnormal glycogen structures called Lafora bodies in the brain, liver, muscle, and sweat glands 2. Disease onset typically occurs in early adolescence with seizures, followed by progressive neurological decline including cognitive deterioration and ataxia 4. The condition is invariably fatal, with death occurring within 10 years of symptom onset 2. Clinical significance is limited by poor responsiveness to antiepileptic drugs. However, recent gene therapy approaches using adeno-associated viral delivery of human EPM2A ameliorated neurological symptoms, reduced epileptic activity, and decreased Lafora body formation in mouse models, representing promising therapeutic potential 1. Therapeutic strategies targeting reduced brain glycogen synthesis appear particularly promising 2.

Sources cited
1
Laforin functions in a complex with malin to control glycogen synthesis and prevent misfolded protein toxicity; gene therapy with EPM2A reduced Lafora bodies and epileptic activity
PMID: 38796707
2
EPM2A mutations cause Lafora disease with polyglucosan accumulation in brain, liver, muscle and sweat glands; disease onset in adolescence is progressive and fatal within 10 years
PMID: 27702709
3
Laforin's role in autophagy and mTOR pathway regulation relates to Lafora disease pathogenesis
PMID: 32671745
4
Lafora disease presents as progressive myoclonus epilepsy with progressive cognitive decline and ataxia; has invariably fatal course
PMID: 26060909
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
myoclonic epilepsy of Lafora 1Open Targets
0.81Strong
Lafora diseaseOpen Targets
0.75Strong
Progressive myoclonic epilepsyOpen Targets
0.55Moderate
genetic disorderOpen Targets
0.49Moderate
neurodegenerative diseaseOpen Targets
0.42Moderate
Alzheimer diseaseOpen Targets
0.41Moderate
lysosomal storage diseaseOpen Targets
0.40Weak
multiple sclerosisOpen Targets
0.40Weak
Parkinson diseaseOpen Targets
0.40Weak
disorder of glycogen metabolismOpen Targets
0.37Weak
Rolandic epilepsyOpen Targets
0.33Weak
self-limited epilepsy with centrotemporal spikesOpen Targets
0.33Weak
Abnormality of the skeletal systemOpen Targets
0.28Weak
Abnormality of the nervous systemOpen Targets
0.27Weak
Unverricht-Lundborg diseaseOpen Targets
0.27Weak
skull disorderOpen Targets
0.27Weak
hair colorOpen Targets
0.26Weak
diabetes mellitusOpen Targets
0.26Weak
fungal infectious diseaseOpen Targets
0.26Weak
lower urinary tract calculusOpen Targets
0.19Weak
Myoclonic epilepsy of lafora 1UniProt
Pathogenic Variants56
NM_005670.4(EPM2A):c.108_139del (p.Ala37fs)Pathogenic
Progressive myoclonic epilepsy|Lafora disease|Myoclonic epilepsy of Lafora 1
β˜…β˜…β˜†β˜†2026β†’ Residue 37
NM_005670.4(EPM2A):c.466_469dup (p.Tyr157fs)Pathogenic
not provided|Progressive myoclonic epilepsy
β˜…β˜…β˜†β˜†2026β†’ Residue 157
NM_005670.4(EPM2A):c.721C>T (p.Arg241Ter)Pathogenic
Lafora disease|not provided|Progressive myoclonic epilepsy|Inborn genetic diseases|EPM2A-related disorder|Myoclonic epilepsy of Lafora 1
β˜…β˜…β˜†β˜†2025β†’ Residue 241
NM_005670.4(EPM2A):c.878A>T (p.Gln293Leu)Likely pathogenic
not provided|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 293
NM_005670.4(EPM2A):c.512G>A (p.Arg171His)Pathogenic
Lafora disease|Progressive myoclonic epilepsy|Myoclonic epilepsy of Lafora 1|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 171
NM_005670.4(EPM2A):c.495G>A (p.Trp165Ter)Pathogenic
not provided|Progressive myoclonic epilepsy|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 165
NM_005670.4(EPM2A):c.92_124del (p.Arg31_Arg41del)Pathogenic
not provided|Progressive myoclonic epilepsy
β˜…β˜…β˜†β˜†2025β†’ Residue 31
NM_005670.4(EPM2A):c.322C>T (p.Arg108Cys)Pathogenic
Progressive myoclonic epilepsy|Myoclonic epilepsy of Lafora 1|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 108
NM_005670.4(EPM2A):c.118del (p.Arg39_Leu40insTer)Pathogenic
Progressive myoclonic epilepsy|not provided|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 39
NM_005670.4(EPM2A):c.94T>G (p.Trp32Gly)Pathogenic
not provided|Myoclonic epilepsy of Lafora 1|Progressive myoclonic epilepsy|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 32
NM_005670.4(EPM2A):c.269_275del (p.Lys90fs)Pathogenic
not provided|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 90
NM_005670.4(EPM2A):c.163C>T (p.Gln55Ter)Pathogenic
not provided|Lafora disease|Progressive myoclonic epilepsy|Myoclonic epilepsy of Lafora 1
β˜…β˜…β˜†β˜†2025β†’ Residue 55
NM_005670.4(EPM2A):c.166G>T (p.Glu56Ter)Pathogenic
not provided|Myoclonic epilepsy of Lafora 1|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 56
NM_005670.4(EPM2A):c.258C>G (p.Tyr86Ter)Pathogenic
Progressive myoclonic epilepsy|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 86
NM_005670.4(EPM2A):c.301+1G>TPathogenic
Progressive myoclonic epilepsy|not provided|Lafora disease
β˜…β˜…β˜†β˜†2025
NM_005670.4(EPM2A):c.179G>A (p.Trp60Ter)Pathogenic
Lafora disease|Progressive myoclonic epilepsy
β˜…β˜…β˜†β˜†2025β†’ Residue 60
NM_005670.4(EPM2A):c.302-1G>CPathogenic
Progressive myoclonic epilepsy|Lafora disease
β˜…β˜…β˜†β˜†2025
NM_005670.4(EPM2A):c.302-2A>GPathogenic
Progressive myoclonic epilepsy|Lafora disease
β˜…β˜…β˜†β˜†2025
NM_005670.4(EPM2A):c.363_364dup (p.Tyr122fs)Pathogenic
Progressive myoclonic epilepsy|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 122
NM_005670.4(EPM2A):c.835G>T (p.Gly279Cys)Pathogenic
Progressive myoclonic epilepsy|Lafora disease
β˜…β˜…β˜†β˜†2025β†’ Residue 279
View on ClinVar β†—
Related Genes
PPP1R3CProtein interaction91%GYG2Protein interaction91%GSK3BProtein interaction80%STBD1Protein interaction78%NFU1Protein interaction77%AGLProtein interaction76%
Tissue Expression6 tissues
Heart
100%
Brain
40%
Liver
18%
Ovary
14%
Lung
11%
Bone Marrow
9%
Gene Interaction Network
Click a node to explore
EPM2APPP1R3CGYG2GSK3BSTBD1NFU1AGL
PROTEIN STRUCTURE
Preparing viewer…
PDB4R30 Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.19LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.83 [0.59–1.19]
RankingsWhere EPM2A stands among ~20K protein-coding genes
  • #4,834of 20,598
    Most Researched99 Β· top quartile
  • #1,228of 5,498
    Most Pathogenic Variants56 Β· top quartile
  • #12,504of 17,882
    Most Constrained (LOEUF)1.19
Genes detectedEPM2A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Glycogen metabolism and structure: A review.
PMID: 39245499
Carbohydr Polym Β· 2024
1.00
2
Glycogen and its metabolism: some new developments and old themes.
PMID: 22248338
Biochem J Β· 2012
0.90
3
Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances.
PMID: 38397161
Genes (Basel) Β· 2024
0.80
4
Muscle glycogenoses.
PMID: 11439374
Muscle Nerve Β· 2001
0.70
5
Lafora disease.
PMID: 27702709
Epileptic Disord Β· 2016
0.60