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

Summary

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; MELF2
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: mouse all
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Genomic context

Location:: 6q24.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (145383353..145736023, complement)
RS_2023_10	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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

EPM2A in-frame deletion slows neurological decline in Lafora Disease.
Title: EPM2A in-frame deletion slows neurological decline in Lafora Disease.
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.
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.
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.
Laforin-glycan interactions occur with a favourable enthalpic contribution counter-balanced by an unfavourable entropic contribution.
Title: Biophysical characterization of laforin-carbohydrate interaction.
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.
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.
This study suggest that variations in phenotypes of EPM2A-deficient Lafora disease.
Title: Late onset Lafora disease and novel EPM2A mutations: breaking paradigms.
novel molecular determinants in the laforin active site that help decipher the mechanism of glucan phosphatase activity.
Title: Dimeric quaternary structure of human laforin.
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
Myoclonic epilepsy of Lafora 1 MedGen: CN377204 OMIM: 254780 GeneReviews: Progressive Myoclonus Epilepsy, Lafora Type	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-132306 (e-PCR)
- UniSTS:170771

D10S275 (e-PCR)
- UniSTS:147992

SHGC-83278 (e-PCR)
- UniSTS:101156

SHGC-78150 (e-PCR)
- UniSTS:101192

RH122690 (e-PCR)
- UniSTS:133968

RH103579 (e-PCR)
- UniSTS:97904

SHGC-144778 (e-PCR)
- UniSTS:172413

D6S1443 (e-PCR)
- UniSTS:83138

AL035166 (e-PCR)
- UniSTS:94679

WI-13634 (e-PCR)
- UniSTS:1244

D6S1703 (e-PCR), detects polymorphism
- UniSTS:74211

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

EC 3.1.3.16

EC 3.1.3.48

NP_001346986.1

EC 3.1.3.16

EC 3.1.3.48

NP_001346993.1

EC 3.1.3.16

EC 3.1.3.48

NP_001347000.1

EC 3.1.3.16

EC 3.1.3.48

NP_001355058.1

EC 3.1.3.16

EC 3.1.3.48

NP_001355059.1

EC 3.1.3.16

EC 3.1.3.48

NP_001355060.1

EC 3.1.3.16

EC 3.1.3.48

NP_001355061.1

EC 3.1.3.16

EC 3.1.3.48

NP_005661.1

EC 3.1.3.16

EC 3.1.3.48

XP_011534415.1

EC 3.1.3.16

EC 3.1.3.48

XP_011534418.1

EC 3.1.3.16

EC 3.1.3.48

XP_016866791.1

EC 3.1.3.16

EC 3.1.3.48

XP_024302318.1

EC 3.1.3.16

EC 3.1.3.48

XP_024302319.1

EC 3.1.3.16

EC 3.1.3.48

XP_047275319.1

EC 3.1.3.16

EC 3.1.3.48

XP_047275320.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212398.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212399.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212400.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212401.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212402.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212403.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212404.1

EC 3.1.3.16

EC 3.1.3.48

XP_054212405.1

EC 3.1.3.16

EC 3.1.3.48

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

NG_012832.3 RefSeqGene

Range

5503..115718

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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 ...
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

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 ...
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

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

Status: REVIEWED

Source sequence(s)

AL023806, AL365193
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
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
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

B3KMU5, B4DRZ2, O95278, O95483, Q5T3F5, Q6IS15, Q8IU96, Q8IX24, Q8IX25, Q9BS66, 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

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_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

145383353..145736023 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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

See identical proteins and their annotated locations for XP_011534418.1

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 ...
XM_047419364.1 → XP_047275320.1 laforin isoform X5
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
XM_047419363.1 → XP_047275319.1 laforin isoform X3