EFNB2

Chr 13

ephrin B2

Also known as: EPLG5, HTKL, Htk-L, LERK5, ephrin-B2

NCBI Gene: 1948ENSG00000125266UniProt: P52799

This gene encodes ephrin-B2, a transmembrane ligand that binds to Eph receptor tyrosine kinases and mediates bidirectional cell signaling crucial for neuronal migration, vascular development, and heart morphogenesis. Mutations cause autosomal dominant capillary malformation-arteriovenous malformation syndrome, which presents with vascular malformations affecting skin and potentially brain, heart, and other organs. The gene is highly constrained against loss-of-function variants, reflecting its essential role in development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
25
Pubs (1 yr)
111
P/LP submissions
0%
P/LP missense
0.22
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— EFNB2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
111 unique Pathogenic / Likely Pathogenic· 34 VUS of 156 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.988
Z-score 3.40
OE 0.00 (0.00–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.83Z-score
OE missense 0.64 (0.55–0.74)
127 obs / 199.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.22)
0≤0.351.4
Missense OE0.64 (0.55–0.74)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 0 / 13.4Missense obs/exp: 127 / 199.7Syn Z: -0.64
DN
0.3792th %ile
GOF
0.4677th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic109
Likely Pathogenic2
VUS34
Likely Benign6
Benign1
109
Pathogenic
2
Likely Pathogenic
34
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
109
0
109
Likely Pathogenic
0
0
2
0
2
VUS
0
26
8
0
34
Likely Benign
0
0
2
4
6
Benign
0
0
0
1
1
Total0261215152

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

View in ClinVar →

Protein Context — Lollipop Plot

EFNB2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients