EPHA7

Chr 6

EPH receptor A7

Also known as: EHK-3, EHK3, EK11, HEK11

NCBI Gene: 2045ENSG00000135333UniProt: Q15375

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. Increased expression of this gene is associated with multiple forms of carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

121
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EPHA7
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 99 VUS of 121 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.13LOEUF
pLI 1.000
Z-score 6.24
OE 0.04 (0.02–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
2.39Z-score
OE missense 0.71 (0.65–0.77)
385 obs / 541.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.04 (0.02–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.65–0.77)
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.1.04
0≤1.21.6
LoF obs/exp: 2 / 49.3Missense obs/exp: 385 / 541.2Syn Z: -0.38

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS99
Likely Benign4
Benign5
13
Pathogenic
99
VUS
4
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
0
92
7
0
99
Likely Benign
0
1
1
2
4
Benign
0
2
1
2
5
Total095224121

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

View in ClinVar →

Protein Context — Lollipop Plot

EPHA7 · 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
Transcriptomics-Based Liquid Biopsy for Early Detection of Recurrence in Locally Advanced Gastric Cancer.
Ding P et al.·Adv Sci (Weinh)
2024
Targeted demethylation of the EphA7 promoter inhibits tumorigenesis via the SP1/DNMT1 and PI3K/AKT axes and improves the response to multiple therapies in cervical cancer.
Zhang W et al.·Cell Death Dis
2025
Membrane Proteome-Wide Screening of Autoantibodies in CIDP Using Human Cell Microarray Technology.
Caballero-Ávila M et al.·Neurol Neuroimmunol Neuroinflamm
2024
The identification and validation of EphA7 hypermethylation, a novel biomarker, in cervical cancer.
Zhang W et al.·BMC Cancer
2022
EPHA7 haploinsufficiency is associated with a neurodevelopmental disorder.
Lévy J et al.·Clin Genet
2021
EPHA7 mutation as a predictive biomarker for immune checkpoint inhibitors in multiple cancers.
Zhang Z et al.·BMC Med
2021
MTDH and EphA7 are markers for metastasis and poor prognosis of gallbladder adenocarcinoma.
Liu DC et al.·Diagn Cytopathol
2013
Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma.
Hojný J et al.·Mod Pathol
2025
[Expression of EphA7 protein in primary hepatocellular carcinoma and its clinical significance].
Zhang SJ et al.·Zhonghua Wai Ke Za Zhi
2010
Genetic aberrations in small B-cell lymphomas and leukemias: molecular pathology, clinical relevance and therapeutic targets.
Bogusz AM et al.·Leuk Lymphoma
2016Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Comprehensive analysis of Ephrin ligand and receptor expression reveals exclusive domains during nephrogenesis for epha4/epha7 and efna3.
Le Bouffant R et al.·Int J Dev Biol
2025
Chidamide impedes the progression of non-small cell lung cancer by inhibiting the METTL3/EPHA7 pathway.
Ren T et al.·J Chemother
2025
Knockdown of miR-204-5p promotes nerve regeneration and functional recovery after hypoxic-ischemic brain damage in neonatal rats via the Wnt2/Ephrin-A2/EphA7 pathway.
He M et al.·Neuroreport
2025🔓 Open AccessFunctional
Ephrin-A5 or EphA7 stimulation is anti-proliferative for human rhabdomyosarcoma in vitro.
Cecchini A et al.·Skelet Muscle
2025🔓 Open Access
tRFAla-AGC-3-M8 attenuates neuroinflammation and neuronal damage in Alzheimer's disease via the EphA7-ERK1/2-p70S6K signaling pathway.
Deng Z et al.·Alzheimers Res Ther
2025🔓 Open Access
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