EFNB2
protein-codingephrin B2, the group of Ephrins
Gene summary
This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNB class ephrin which binds to the EPHB4 and EPHA3 receptors. [provided by RefSeq, Jul 2008]
- EPLG5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*EFNB2* was first reported in relation to autosomal dominant syndromic congenital heart disease in 2018 (PMID: 29508392). There is one proband included in this curation who expressed a hypoplastic left ventricle that required surgery at two months old, and was found to have a missense variant in *EFNB2* (PMID: 29508392). The gene-disease relationship is supported by two mouse models, mouse model functional alteration, and expression data (PMIDs: 11880349, 15223333, 27530629, 9630219). In summary, there is limited evidence to support this gene-disease relationship due to a lack of *EFNB2* variants found and reported in patients. More evidence is needed to either support or refute the role *EFNB2* plays in human syndromic congenital heart disease. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date March 3rd, 2026 (SOP Version 12)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EFNB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004093.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 5 | |||
| missense | 26 | 26 | ||||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 28 | 4 | 0 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004084.1 | 5 | MANE Select | |
| Ensembl | ENSP00000493716.1 | 5 | MANE Select | |
| RefSeq | NP_001358985.1 | 4 | Standard | |
| RefSeq | NP_001358986.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| efnb2a | Danio rerio | Structure: commissure of the tract of the commissure of the caudal tuberculum Quality: has extra parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Spinal Cord Injury
- Developmental Biology
- EPH-Ephrin signaling
- Ephrin signaling
Biological Process
- lymph vessel development
- cell migration involved in sprouting angiogenesis
- cell adhesion
- cell-cell signaling
- axon guidance
Molecular Function
- virus receptor activity
- protein tyrosine kinase activity
- protein binding
- ephrin receptor binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- focal adhesion
- Schaffer collateral - CA1 synapse
- glutamatergic synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000245323
- Coding exons
- 5
- Length
- 45384
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.83 | 127 | 200 | 0.636 | 0.0000113 | 2177 |
| Missense (PolyPhen) | 36 | 81.325 | 0.44267 | 899 | ||
| Synonymous | -0.645 | 94 | 86.4 | 1.09 | 0.00000592 | 647 |
| Loss of Function | 3.40 | 0 | 13.4 | 0.00 | 5.65e-7 | 176 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons. {ECO:0000269|PubMed:12734395}.;
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- LoFtool
- 0.0354
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 21.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.876
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |