EPHA10

Chr 1AD

EPH receptor A10

Also known as: DFNA88

NCBI Gene: 284656 ENSG00000183317 UniProt: Q5JZY3 OMIM: 611123

The EPHA10 protein is a receptor tyrosine kinase that binds to ephrin-A ligands and mediates cell-cell communication regulating cell attachment and mobility in neuronal and epithelial cells. Mutations cause autosomal dominant deafness (DFNA88), though the association remains provisional. The gene shows tolerance to loss-of-function variants based on constraint metrics.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Ephrin receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility in neuronal and epithelial cells (Aasheim et al., 2005 [PubMed 15777695]). See MIM 179610 for additional background on Eph receptors and ephrins.[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 1.291 OMIM phenotype

Clinical Summary— EPHA10

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 162 VUS of 206 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.07

OE 0.99 (0.77–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.91Z-score

OE missense 0.89 (0.83–0.96)

512 obs / 573.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.99 (0.77–1.29)

0≤0.351.4

Missense OE?0.89 (0.83–0.96)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 40 / 40.5Missense obs/exp: 512 / 573.0Syn Z: 0.05

This gene — mechanism propensity

0.6258th %ile

GOF

0.7126th %ile

LOF

0.3745th %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

206 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS162

Likely Benign7

Benign2

Pathogenic

162

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	2	160	0	0	162
Likely Benign	0	3	0	4	7
Benign	0	2	0	0	2
Total	2	165	1	4	172

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

5 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap EPHA10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →