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EPHB4 EPH receptor B4 [ Homo sapiens (human) ]

Gene ID: 2050, updated on 10-May-2026
Official Symbol
EPHB4provided by HGNC
Official Full Name
EPH receptor B4provided by HGNC
Primary source
HGNC:HGNC:3395
See related
Ensembl:ENSG00000196411 MIM:600011; AllianceGenome:HGNC:3395
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HTK; MYK1; HFASD; CMAVM2; LMPHM7; TYRO11
Summary
Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. 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. The Eph family of 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. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in placenta (RPKM 28.2), endometrium (RPKM 22.9) and 24 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See EPHB4 in Genome Data Viewer
Location:
7q22.1
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (100802565..100827523, complement)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (102042646..102067608, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (100400187..100425145, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr7:100322454-100322688 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26383 Neighboring gene erythropoietin Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26384 Neighboring gene zonadhesin Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100382347-100382846 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr7:100391649-100392196 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26385 Neighboring gene Sharpr-MPRA regulatory region 9506 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100399088-100399791 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100399792-100400494 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100402349-100403064 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:100403701-100404900 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100412721-100413220 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100425149-100425944 Neighboring gene RNA, 7SL, cytoplasmic 750, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100426741-100427536 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100432899-100433818 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100433819-100434738 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100434739-100435658 Neighboring gene solute carrier family 12 member 9 Neighboring gene SLC12A9 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26388 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26389 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18463 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100456152-100456652 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100456653-100457153 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100457811-100458310 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100458529-100459030 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18464 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18465 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26390 Neighboring gene microRNA 6875 Neighboring gene thyroid hormone receptor interactor 6

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Down-regulation of EphB4 phosphorylation is necessary for esophageal squamous cell carcinoma tumorigenecity. Hu F, et al. Tumour Biol, 2014 Jul. PMID 24771266
  2. Expression of the EPHB4 receptor tyrosine kinase in head and neck and renal malignancies--implications for solid tumors and potential for therapeutic inhibition. Ferguson BD, et al. Growth Factors, 2014 Dec. PMID 25391996, Free PMC Article
  3. EPHB4 tyrosine-kinase receptor expression and biological significance in soft tissue sarcoma. Becerikli M, et al. Int J Cancer, 2015 Apr 15. PMID 25274141
  4. Phenotype of CM-AVM2 caused by variants in EPHB4: how much overlap with hereditary hemorrhagic telangiectasia (HHT)? Wooderchak-Donahue WL, et al. Genet Med, 2019 Sep. PMID 30760892
  5. Ligand-dependent EphB4 activation serves as an anchoring signal in glioma cells. Kawahara Y, et al. Cancer Lett, 2019 May 1. PMID 30776480

See all (205) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Biological Significance of EphB4 Expression in Cancer.
    Title: Biological Significance of EphB4 Expression in Cancer.
  2. SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology.
    Title: SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology.
  3. Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation and Novel Mutations in Cerebral Cavernous Malformations: In Vitro and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell Pathophysiology.
    Title: Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation and Novel Mutations in Cerebral Cavernous Malformations: In Vitro and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell Pathophysiology.
  4. Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
    Title: Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
  5. Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with EPHB4 pathogenic variants.
    Title: Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with EPHB4 pathogenic variants.
  6. Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.
    Title: Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.
  7. Mutations in EPHB4 cause human venous valve aplasia.
    Title: Mutations in EPHB4 cause human venous valve aplasia.
  8. EphrinB2-EphB4 Signaling in Neurooncological Disease.
    Title: EphrinB2-EphB4 Signaling in Neurooncological Disease.
  9. EPHB4 mutation causes adult and adolescent-onset primary lymphedema.
    Title: EPHB4 mutation causes adult and adolescent-onset primary lymphedema.
  10. Transcriptional and Post-Translational Control Mechanisms for EphB4 Expression in Physiology and Cancer Disease.
    Title: Transcriptional and Post-Translational Control Mechanisms for EphB4 Expression in Physiology and Cancer Disease.
Submit: New GeneRIF Correction See all GeneRIFs (136)

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ephrin receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ephrin receptor activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables transmembrane receptor protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables transmembrane receptor protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables transmembrane receptor protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in angiogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in angiogenesis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in angiogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in angiogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cell adhesion IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell migration involved in sprouting angiogenesis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell surface receptor protein tyrosine kinase signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in ephrin receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ephrin receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ephrin receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in heart morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in heart morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
part_of signaling receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
  
Preferred Names
ephrin type-B receptor 4
Names
ephrin receptor EphB4
hepatoma transmembrane kinase
tyrosine-protein kinase TYRO11
tyrosine-protein kinase receptor HTK
NP_004435.3
XP_016867305.1
XP_054213436.1

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_052671.1 RefSeqGene

    Range
    4999..29957
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_004444.5 → NP_004435.3  ephrin type-B receptor 4 precursor

    See identical proteins and their annotated locations for NP_004435.3

    Status: REVIEWED

    Source sequence(s)
    AC011895, AY056048, BC052804, CB962032
    Consensus CDS
    CCDS5706.1
    UniProtKB/Swiss-Prot
    B5A970, B5A971, B5A972, P54760, Q7Z635, Q9BTA5, Q9BXP0
    UniProtKB/TrEMBL
    Q541P7, Q59F17
    Related
    ENSP00000350896.3, ENST00000358173.8
    Conserved Domains (5) summary
    cd05065
    Location:610 → 878
    PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors
    cd09554
    Location:907 → 973
    SAM_EPH-B4; SAM domain of EPH-B4 subfamily of tyrosine kinase receptors
    cd10474
    Location:17 → 196
    EphR_LBD_B4; Ligand Binding Domain of Ephrin type-B Receptor 4
    cd00063
    Location:434 → 526
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
    pfam14575
    Location:564 → 610
    EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    100802565..100827523 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017011816.2 → XP_016867305.1  ephrin type-B receptor 4 isoform X1

    UniProtKB/TrEMBL
    Q59F17
    Related
    ENSP00000526950.1, ENST00000856891.1
    Conserved Domains (7) summary
    cd05065
    Location:628 → 896
    PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors
    cd09554
    Location:925 → 991
    SAM_EPH-B4; SAM domain of EPH-B4 subfamily of tyrosine kinase receptors
    smart00454
    Location:922 → 989
    SAM; Sterile alpha motif
    cd10474
    Location:17 → 196
    EphR_LBD_B4; Ligand Binding Domain of Ephrin type-B Receptor 4
    cd00063
    Location:452 → 544
    FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
    pfam07714
    Location:633 → 892
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14575
    Location:582 → 628
    EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    102042646..102067608 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054357461.1 → XP_054213436.1  ephrin type-B receptor 4 isoform X1

    UniProtKB/TrEMBL
    Q59F17
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P54760.2 GenPept UniProtKB/Swiss-Prot:P54760

Gene LinkOut

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