EPHA1

Chr 7

EPH receptor A1

Also known as: EPH, EPHT, EPHT1

NCBI Gene: 2041ENSG00000146904UniProt: P21709

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene is expressed in some human cancer cell lines and has been implicated in carcinogenesis. [provided by RefSeq, Jul 2008]

171
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EPHA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 151 VUS of 171 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.04LOEUF
pLI 0.000
Z-score 1.29
OE 0.81 (0.63–1.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.22Z-score
OE missense 0.97 (0.91–1.04)
574 obs / 589.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.81 (0.63–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.91–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 41 / 50.9Missense obs/exp: 574 / 589.2Syn Z: 0.01

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS151
Likely Benign8
11
Pathogenic
1
Likely Pathogenic
151
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
0
149
2
0
151
Likely Benign
0
8
0
0
8
Benign
0
0
0
0
0
Total0157140171

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

View in ClinVar →

Protein Context — Lollipop Plot

EPHA1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Functions of EphA1 Receptor Tyrosine Kinase in Several Tumors.
Wu Y et al.·Curr Med Chem
2023Review
A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease.
Hampel H et al.·Front Immunol
2020Review
Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function.
Owens HA et al.·Alzheimers Dement
2024
Genetic characterization of thymoma.
Yu L et al.·Sci Rep
2019
Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance.
Wang YC et al.·Med Sci Monit
2020
Genetics of Alzheimer's disease.
Chouraki V et al.·Adv Genet
2014Review
Alzheimer's Disease rs11767557 Variant Regulates EPHA1 Gene Expression Specifically in Human Whole Blood.
Liu G et al.·J Alzheimers Dis
2018
Genomics of Alzheimer Disease: A Review.
Rosenberg RN et al.·JAMA Neurol
2016Review
Whole-Exome Sequencing of an Exceptional Longevity Cohort.
Nygaard HB et al.·J Gerontol A Biol Sci Med Sci
2019Cohort
Ephrin and Eph receptor signaling in female reproductive physiology and pathology†.
Adu-Gyamfi EA et al.·Biol Reprod
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools