EPM2A
Laforin, a dual-specificity phosphatase involved in glycogen metabolism and progressive myoclonus epilepsy
Gene Information Card
| Symbol | EPM2A |
|---|---|
| Full Name | EPM2A, laforin glucan phosphatase |
| Gene Type | Protein coding |
| Chromosomal Location | 6q24.3 |
| NCBI Gene ID | 7957 ncbi.nlm.nih.gov/gene/7957 |
| Ensembl ID | ENSG00000198959 |
| UniProt ID | O95278 |
| OMIM ID | 607566 |
| HGNC ID | 3413 |
| Aliases | EPM2, EPM2A, MELF, laforin |
Description
EPM2A encodes laforin, a dual-specificity phosphatase that dephosphorylates glycogen and regulates glycogen metabolism. Mutations in EPM2A cause Lafora disease, a progressive myoclonus epilepsy with polyglucosan body accumulation. Laforin interacts with malin (NHLRC1) to control glycogen synthesis and prevent aberrant glycogen accumulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lafora disease (progressive myoclonus epilepsy type 2) | Loss-of-function mutations in EPM2A impair laforin phosphatase activity, leading to accumulation of polyglucosan bodies (Lafora bodies) in neurons and other tissues, causing epilepsy and neurodegeneration. | ClinVar, OMIM |
| Progressive myoclonus epilepsy | EPM2A mutations disrupt glycogen dephosphorylation, resulting in hyperphosphorylated glycogen and Lafora body formation, which triggers seizure activity and neurological decline. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Muscle | 8.3 | Medium |
| Liver | 6.1 | Low |
| Heart | 5.4 | Low |
| Kidney | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.1 | Neuronal model |
| HEK293 (embryonic kidney) | 7.8 | Common expression system |
| HepG2 (hepatocellular carcinoma) | 5.6 | Liver-derived |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.241G>A (p.Gly81Arg) | Missense | Rare | Loss of phosphatase activity; associated with Lafora disease |
| c.905C>T (p.Pro302Leu) | Missense | Rare | Impaired malin binding; Lafora disease |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; severe Lafora disease |
| c.736_737del (p.Leu246fs) | Frameshift | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most EPM2A mutations are loss-of-function, reducing or abolishing laforin phosphatase activity, leading to Lafora disease.
Gain of Function (GOF)
No gain-of-function mutations reported for EPM2A.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • dual-specificity phosphatase activity | • glycogen binding |
| • glycogen dephosphorylation | • protein phosphatase activity |
| • cytoplasm | • nucleus |
Pathways
• Glycogen metabolism
• Lafora disease pathway
Protein Summary
Laforin is a 331-amino acid dual-specificity phosphatase with a carbohydrate-binding domain (CBM20) that targets glycogen. It dephosphorylates glycogen to prevent hyperphosphorylation and Lafora body formation. Laforin also interacts with malin (NHLRC1) to ubiquitinate and degrade glycogen synthase. Loss of laforin function leads to progressive myoclonus epilepsy (Lafora disease).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPM2AIP1 Knockout HEK293 Cell Line | EDJ-KQ3529 | Human | 9852 | Details Get a Quote |
| EPM2A Knockout HEK293 Cell Line | EDJ-KQ6149 | Human | 7957 | Details Get a Quote |
| EPM2A Knockout A-549 Cell Line | EDJ-KQ29948 | Human | 7957 | Details Get a Quote |
| EPM2A Knockout HeLa Cell Line | EDJ-KQ29950 | Human | 7957 | Details Get a Quote |
| EPM2AIP1 Knockout A-549 Cell Line | EDJ-KQ25370 | Human | 9852 | Details Get a Quote |
| EPM2AIP1 Knockout HCT 116 Cell Line | EDJ-KQ25371 | Human | 9852 | Details Get a Quote |
| EPM2AIP1 Knockout HeLa Cell Line | EDJ-KQ25372 | Human | 9852 | Details Get a Quote |
| EPM2A Knockout HCT 116 Cell Line | EDJ-KQ28639 | Human | 7957 | Details Get a Quote |
