EPM2A

EPM2A glucan phosphatase, laforin, the group of Atypical dual specificity phosphatases

Basic information

Region (hg38): 6:145382535-145736023

Links

ENSG00000112425 ∙ NCBI:7957 ∙ OMIM:607566 ∙ HGNC:3413 ∙ Uniprot:B3EWF7, O95278 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lafora disease (Definitive), mode of inheritance: AR
• Lafora disease (Strong), mode of inheritance: AR
• Lafora disease (Strong), mode of inheritance: AR
• Lafora disease (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoclonic epilepsy of Lafora 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	9771710; 10513696; 14663053; 15277643; 16157917; 16356781; 20301563
Some antiepileptic drugs may be effective, but certain medications (eg, phenytoin, and possibly carbamazepine, oxcarbazepine, and lamotrigine) can exacerbate myoclonus

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPM2A gene.

• Progressive_myoclonic_epilepsy (359 variants)
• not_provided (109 variants)
• Inborn_genetic_diseases (92 variants)
• Lafora_disease (71 variants)
• not_specified (34 variants)
• Myoclonic_epilepsy_of_Lafora_1 (26 variants)
• EPM2A-related_disorder (12 variants)
• Intellectual_disability (2 variants)
• Cataract (1 variants)
• Self-limited_epilepsy_with_centrotemporal_spikes (1 variants)
• Microcephaly (1 variants)
• Severe_global_developmental_delay (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Seizure (1 variants)
• Myoclonic_epilepsy,_progressive,_X-linked (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPM2A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005670.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	125	1	127
missense	3	21	212	7	1	244
nonsense	8	6	1			15
start loss						0
frameshift	12	7	1			20
splice donor/acceptor (+/-2bp)	4	2	1			7
Total	27	36	216	132	2

Highest pathogenic variant AF is 0.00010781858

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPM2A	protein_coding	protein_coding	ENST00000367519	4	234442

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.260	165	156	1.06	0.00000893	2124
Missense in Polyphen		64	59.944	1.0677		676
Synonymous	-1.64	78	61.6	1.27	0.00000373	660
Loss of Function	0.733	9	11.7	0.769	5.89e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000265	0.000264
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000223	0.000220
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Pathway: Metabolism of carbohydrates;Metabolism;Glycogen synthesis;Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.325

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.675

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: positive regulation of macroautophagy;negative regulation of TOR signaling
• Cellular component: nucleus
• Molecular function: protein binding