EPHB6

Chr 7

EPH receptor B6

Also known as: HEP

NCBI Gene: 2051ENSG00000106123UniProt: O15197

This gene encodes a member of a family of transmembrane proteins that function as receptors for ephrin-B family proteins. Unlike other members of this family, the encoded protein does not contain a functional kinase domain. Activity of this protein can influence cell adhesion and migration. Expression of this gene is downregulated during tumor progression, suggesting that the protein may suppress tumor invasion and metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

196
ClinVar variants
47
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EPHB6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 Pathogenic / Likely Pathogenic· 142 VUS of 196 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.
0.62LOEUF
pLI 0.000
Z-score 3.66
OE 0.42 (0.30–0.62)
Tolerant

Typical tolerance to LoF variation

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.
0.98Z-score
OE missense 0.89 (0.83–0.95)
535 obs / 602.7 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.0.42 (0.30–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.83–0.95)
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.1.07
0≤1.21.6
LoF obs/exp: 20 / 47.1Missense obs/exp: 535 / 602.7Syn Z: -0.91

ClinVar Variant Classifications

196 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic1
VUS142
Likely Benign7
46
Pathogenic
1
Likely Pathogenic
142
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
1
0
1
VUS
0
136
6
0
142
Likely Benign
0
7
0
0
7
Benign
0
0
0
0
0
Total0143530196

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

View in ClinVar →

Protein Context — Lollipop Plot

EPHB6 · 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
Reduced EphB6 protein in gastric carcinoma and associated lymph nodes suggests EphB6 as a gastric tumor and metastasis inhibitor.
Liu J et al.·Cancer Biomark
2017
Clinical Significance of EphB4 and EphB6 Expression in Human Malignant and Benign Thyroid Lesions.
Giaginis C et al.·Pathol Oncol Res
2016
High expression of EphB6 protein in tongue squamous cell carcinoma is associated with a poor outcome.
Dong Y et al.·Int J Clin Exp Pathol
2015
EPHB6 mutation induces cell adhesion-mediated paclitaxel resistance via EPHA2 and CDH11 expression.
Yoon S et al.·Exp Mol Med
2019
Implications of EPHB6, EFNB2, and EFNB3 expressions in human neuroblastoma.
Tang XX et al.·Proc Natl Acad Sci U S A
2000
Viewing the Eph receptors with a focus on breast cancer heterogeneity.
Nikas I et al.·Cancer Lett
2018Review
Modulation of liver-intestine cadherin (Cadherin 17) expression, ERK phosphorylation and WNT signaling in EPHB6 receptor-expressing MDA-MB-231 cells.
Bhushan L et al.·Cancer Genomics Proteomics
2014
Receptor tyrosine kinase Ephb6 regulates vascular smooth muscle contractility and modulates blood pressure in concert with sex hormones.
Luo H et al.·J Biol Chem
2012
May EPH/Ephrin Targeting Revolutionize Lung Cancer Treatment?
Psilopatis I et al.·Int J Mol Sci
2022Review
EphB6 receptor significantly alters invasiveness and other phenotypic characteristics of human breast carcinoma cells.
Fox BP et al.·Oncogene
2009
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