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EPM2A EPM2A glucan phosphatase, laforin [ Homo sapiens (human) ]

Gene ID: 7957, updated on 21-Mar-2023

Summary

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Official Symbol
EPM2Aprovided by HGNC
Official Full Name
EPM2A glucan phosphatase, laforinprovided by HGNC
Primary source
HGNC:HGNC:3413
See related
Ensembl:ENSG00000112425 MIM:607566; AllianceGenome:HGNC:3413
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EPM2; MELF
Summary
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]
Expression
Ubiquitous expression in heart (RPKM 6.9), kidney (RPKM 4.5) and 24 other tissues See more
Orthologs
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Genomic context

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See EPM2A in Genome Data Viewer
Location:
6q24.3
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (145383353..145736023, complement)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (146574195..146956629, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (145946441..146057159, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:145218575-145219774 Neighboring gene tRNA-Gln (anticodon TTG) 4-1 Neighboring gene RNA, U1 small nuclear 33, pseudogene Neighboring gene zinc finger protein 131 pseudogene Neighboring gene Sharpr-MPRA regulatory region 3301 Neighboring gene Sharpr-MPRA regulatory region 9117 Neighboring gene uncharacterized LOC105378039 Neighboring gene uncharacterized LOC124901419 Neighboring gene EPM2A divergent transcript

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. EPM2A in-frame deletion slows neurological decline in Lafora Disease. Lomax LB, et al. Seizure, 2021 Oct. PMID 34147889, Free PMC Article
  2. Whole exome sequencing identified a novel missense mutation in EPM2A underlying Lafora disease in a Pakistani family. Aslam Z, et al. Seizure, 2017 Oct. PMID 28934672
  3. A novel EPM2A mutation in a patient with Lafora disease presenting with early parkinsonism symptoms in childhood. Yildiz EP, et al. Seizure, 2017 Oct. PMID 28818698
  4. Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan. Sullivan MA, et al. Int J Mol Sci, 2017 Aug 11. PMID 28800070, Free PMC Article
  5. Clinical and genetic studies in patients with Lafora disease from Pakistan. Ahmad A, et al. J Neurol Sci, 2017 Feb 15. PMID 28131202

See all (96) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. EPM2A in-frame deletion slows neurological decline in Lafora Disease.
    Title: EPM2A in-frame deletion slows neurological decline in Lafora Disease.
  2. Laforin/malin complex interacts physically and co-localizes intracellularly with core components of the PI3KC3 complex (Beclin1, Vps34 and Vps15), and that this interaction is specific and results in the polyubiquitination of these proteins.
    Title: Regulation of the autophagic PI3KC3 complex by laforin/malin E3-ubiquitin ligase, two proteins involved in Lafora disease.
  3. rs702304 and rs2235481 within the EPM2A gene were associated with schizophrenia liability.
    Title: PDE7B, NMBR and EPM2A Variants and Schizophrenia: A Case-Control and Pharmacogenetics Study.
  4. Laforin prevents the auto-degradation of malin by presenting itself as a substrate. Malin preferentially degrades the phosphatase-inactive laforin monomer.
    Title: Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease.
  5. Laforin-glycan interactions occur with a favourable enthalpic contribution counter-balanced by an unfavourable entropic contribution.
    Title: Biophysical characterization of laforin-carbohydrate interaction.
  6. laforin is responsible for glycogen dephosphorylation during exercise and acts during the cytosolic degradation of glycogen
    Title: Muscle glycogen remodeling and glycogen phosphate metabolism following exhaustive exercise of wild type and laforin knockout mice.
  7. Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway.
    Title: Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway.
  8. This study suggest that variations in phenotypes of EPM2A-deficient Lafora disease.
    Title: Late onset Lafora disease and novel EPM2A mutations: breaking paradigms.
  9. novel molecular determinants in the laforin active site that help decipher the mechanism of glucan phosphatase activity.
    Title: Dimeric quaternary structure of human laforin.
  10. The crystal structure of laforin bound to phosphoglucan product, reveals its unique integrated tertiary and quaternary structure.
    Title: Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.
Submit: New GeneRIF Correction See all GeneRIFs (51)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Lafora disease
MedGen: C0751783 OMIM: 254780 GeneReviews: Progressive Myoclonus Epilepsy, Lafora Type
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
acts_upstream_of_or_within negative regulation of TOR signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within positive regulation of macroautophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
laforin
Names
EPM2A, laforin glucan phosphatase
LAFPTPase
epilepsy, progressive myoclonus type 2, Lafora disease (laforin)
epilepsy, progressive myoclonus type 2A, Lafora disease (laforin)
glucan phosphatase
glycogen phosphatase
lafora PTPase
NP_001018051.1
NP_001346986.1
NP_001346993.1
NP_001347000.1
NP_001355058.1
NP_001355059.1
NP_001355060.1
NP_001355061.1
NP_005661.1
XP_011534415.1
XP_011534418.1
XP_016866791.1
XP_024302318.1
XP_024302319.1
XP_047275319.1
XP_047275320.1
XP_054212398.1
XP_054212399.1
XP_054212400.1
XP_054212401.1
XP_054212402.1
XP_054212403.1
XP_054212404.1
XP_054212405.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012832.3 RefSeqGene

    Range
    5503..115718
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001018041.2 → NP_001018051.1  laforin isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks a segment of the coding region compared to variant 1. The resulting isoform (b), also known as C-terISO, contains a shorter and distinct C-terminus compared to isoform a. Isoform b has been localized to the nucleus.
    Source sequence(s)
    AF284580, AF454491, AF454494, AJ130764, BC070047, BI463677
    Consensus CDS
    CCDS87454.1
    UniProtKB/Swiss-Prot
    O95278
    UniProtKB/TrEMBL
    H0Y6I8
    Related
    ENSP00000405913.2, ENST00000435470.2
    Conserved Domains (2) summary
    cd05806
    Location:1 → 129
    CBM20_laforin; Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding ...
    cl21483
    Location:158 → 304
    PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

  2. NM_001360057.2 → NP_001346986.1  laforin isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon in the coding region, resulting in a frameshift and an early start codon, compared to variant 1. It encodes isoform c, which has a shorter and distinct C-terminus, compared to isoform a.
    Source sequence(s)
    AF454491, AF454493, BC005286, BI599200
    Consensus CDS
    CCDS87453.1
    Related
    ENSP00000492876.1, ENST00000638262.1
    Conserved Domains (1) summary
    cd05806
    Location:1 → 129
    CBM20_laforin; Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding ...

  3. NM_001360064.2 → NP_001346993.1  laforin isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform d, which has a shorter N-terminus, compared to isoform a. Variants 4 and 5 encode the same isoform (d).
    Source sequence(s)
    AF454491, AL023806, AL365193
    Consensus CDS
    CCDS87452.1
    UniProtKB/TrEMBL
    H0UI04
    Related
    ENSP00000492701.1, ENST00000639423.1
    Conserved Domains (1) summary
    cl21483
    Location:20 → 166
    PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

  4. NM_001360071.2 → NP_001347000.1  laforin isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform d, which has a shorter N-terminus, compared to isoform a. Variants 4 and 5 encode the same isoform (d).
    Source sequence(s)
    AF454491, AF454493, BC005286, BI599200
    Consensus CDS
    CCDS87452.1
    UniProtKB/TrEMBL
    H0UI04
    Conserved Domains (1) summary
    cl21483
    Location:20 → 166
    PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

  5. NM_001368129.2 → NP_001355058.1  laforin isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variant 10, encodes isoform e.
    Source sequence(s)
    AL023806, AL365193
    Conserved Domains (1) summary
    cd14526
    Location:1 → 158
    DSP_laforin-like; dual specificity phosphatase domain of laforin and similar domains

  6. NM_001368130.1 → NP_001355059.1  laforin isoform f

    Status: REVIEWED

    Source sequence(s)
    AL023806, AL365193

  7. NM_001368131.1 → NP_001355060.1  laforin isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), as well as variants 4 and 5, encodes isoform d.
    Source sequence(s)
    AL023806, AL365193
    Consensus CDS
    CCDS87452.1
    UniProtKB/TrEMBL
    H0UI04

  8. NM_001368132.1 → NP_001355061.1  laforin isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variant 6, encodes isoform e.
    Source sequence(s)
    AL023806, AL365193
    Conserved Domains (1) summary
    cd14526
    Location:1 → 158
    DSP_laforin-like; dual specificity phosphatase domain of laforin and similar domains

  9. NM_005670.4 → NP_005661.1  laforin isoform a

    See identical proteins and their annotated locations for NP_005661.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript, and encodes the longest isoform (a). Isoform a has been localized to the rough endoplasmic reticulum.
    Source sequence(s)
    AF284580, AF454494, BC005286
    Consensus CDS
    CCDS5206.1
    UniProtKB/Swiss-Prot
    O95278, Q9UEN2
    Related
    ENSP00000356489.3, ENST00000367519.9
    Conserved Domains (2) summary
    cd05806
    Location:1 → 129
    CBM20_laforin; Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding ...
    cl21483
    Location:158 → 304
    PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

RNA

  1. NR_153398.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) includes an alternate 5' terminal exon and lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AF454491, AL023806, BC005286, BE268120

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    145383353..145736023 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024446550.2 → XP_024302318.1  laforin isoform X1

    Conserved Domains (1) summary
    cd05806
    Location:1 → 129
    CBM20_laforin; Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding ...

  2. XM_011536113.3 → XP_011534415.1  laforin isoform X2

    Conserved Domains (1) summary
    cd05806
    Location:1 → 129
    CBM20_laforin; Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding ...

  3. XM_024446551.2 → XP_024302319.1  laforin isoform X4

    UniProtKB/TrEMBL
    H0UI04
    Conserved Domains (1) summary
    cl21483
    Location:20 → 166
    PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

  4. XM_011536116.2 → XP_011534418.1  laforin isoform X4

    See identical proteins and their annotated locations for XP_011534418.1

    UniProtKB/Swiss-Prot
    O95278
    UniProtKB/TrEMBL
    H0UI04
    Related
    ENSP00000491353.1, ENST00000638778.1
    Conserved Domains (1) summary
    cl21483
    Location:20 → 166
    PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

  5. XM_047419364.1 → XP_047275320.1  laforin isoform X5

  6. XM_017011302.2 → XP_016866791.1  laforin isoform X5

    UniProtKB/Swiss-Prot
    O95278
    Conserved Domains (1) summary
    cd14526
    Location:1 → 158
    DSP_laforin-like; dual specificity phosphatase domain of laforin and similar domains

  7. XM_047419363.1 → XP_047275319.1  laforin isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    146574195..146956629 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054356424.1 → XP_054212399.1  laforin isoform X1

  2. XM_054356425.1 → XP_054212400.1  laforin isoform X2

  3. XM_054356423.1 → XP_054212398.1  laforin isoform X6

  4. XM_054356428.1 → XP_054212403.1  laforin isoform X4

  5. XM_054356427.1 → XP_054212402.1  laforin isoform X4

  6. XM_054356430.1 → XP_054212405.1  laforin isoform X5

  7. XM_054356429.1 → XP_054212404.1  laforin isoform X5

  8. XM_054356426.1 → XP_054212401.1  laforin isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
B3EWF7.1 GenPept UniProtKB/Swiss-Prot:B3EWF7
O95278.2 GenPept UniProtKB/Swiss-Prot:O95278

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