EHD2

Chr 19

EH domain containing 2

Also known as: PAST2

The protein functions as an ATP- and membrane-binding protein that controls membrane reorganization and trafficking between the plasma membrane and endosomes, and is required for skeletal muscle myoblast fusion. Biallelic mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.538), and the condition typically presents in early infancy with seizures and developmental delays.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.54
Clinical SummaryEHD2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.308
Z-score 2.92
OE 0.23 (0.120.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.88Z-score
OE missense 0.73 (0.660.80)
269 obs / 371.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.120.54)
00.351.4
Missense OE0.73 (0.660.80)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 4 / 17.0Missense obs/exp: 269 / 371.0Syn Z: 0.50
DN
0.6744th %ile
GOF
0.6639th %ile
LOF
0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EHD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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