EPHA3

Chr 3

EPH receptor A3

Also known as: EK4, ETK, ETK1, HEK, HEK4, TYRO4

EPHA3 encodes a receptor tyrosine kinase that binds ephrin-A ligands and regulates cell-cell adhesion, cytoskeletal organization, and cell migration, with key roles in retinotectal neuronal mapping and neuromuscular circuit development. Currently, no established Mendelian diseases have been definitively linked to EPHA3 mutations in the clinical literature. The gene is involved in nervous system development and may have roles in cardiac development through regulation of epithelial-to-mesenchymal transition.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.53
Clinical SummaryEPHA3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.000
Z-score 4.25
OE 0.36 (0.240.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.65Z-score
OE missense 0.92 (0.860.99)
503 obs / 545.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.240.53)
00.351.4
Missense OE0.92 (0.860.99)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 18 / 50.6Missense obs/exp: 503 / 545.9Syn Z: -0.94
DN
0.76top 25%
GOF
0.76top 25%
LOF
0.2777th %ile

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

GOFprediction above median
DNprediction 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

EPHA3 · 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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