EPM2AIP1

Chr 3

EPM2A interacting protein 1

NCBI Gene: 9852 ENSG00000178567 UniProt: Q7L775 OMIM: 607911

EPM2AIP1 encodes a protein that binds to laforin (the EPM2A gene product), though its specific function remains unknown. Mutations cause autosomal recessive progressive myoclonus epilepsy with adolescent onset. The gene is highly constrained against loss-of-function variants, suggesting it plays an important role in neuronal function.

OMIM ResearchSummary from RefSeq

The EPM2A gene, which encodes laforin, is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The protein encoded by this gene binds to laforin, but its function is not known. This gene is intronless. [provided by RefSeq, Oct 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.600

Z-score 3.35

OE 0.20 (0.10–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.44Z-score

OE missense 0.77 (0.70–0.86)

251 obs / 324.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.45)

0≤0.351.4

Missense OE?0.77 (0.70–0.86)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 4 / 20.3Missense obs/exp: 251 / 324.2Syn Z: -1.60

Background carrier burden — how many people carry a rare variant somewhere in EPM2AIP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

724 rare PASS variants

Rare truncating (LoF)

1 in 4,300

67 rare PASS variants

Rare synonymous (reference)

1 in 180

327 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EPM2AIP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 5,600
South Asian	~43k	1 in 110	1 in 910
Remaining (unassigned)	~30k	1 in 140	1 in 2,900
European (Finnish)	~27k	1 in 290	≈ 1 in 13,000
Admixed American	~22k	1 in 190	1 in 2,800
African / African American	~21k	1 in 120	≈ 1 in 10,000
East Asian	~20k	1 in 120	1 in 510
Ashkenazi Jewish	~13k	1 in 720	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 130	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓