EPHB2

EPH receptor B2, the group of Sterile alpha motif domain containing|EPH receptors|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:22710838-22921500

Previous symbols: [ "DRT", "ERK", "EPHT3" ]

Links

ENSG00000133216 ∙ NCBI:2048 ∙ OMIM:600997 ∙ HGNC:3393 ∙ Uniprot:P29323 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• bleeding disorder, platelet-type, 22 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bleeding disorder, platelet-type, 22	AR	Hematologic	Individuals have been described with spontaneous subcutaneous bleeding as well as excessive bleeding after minor injuries, and awareness may allow preventative measures to avoid sequelae, as well as other management options (e.g., iron treatment has been described in one patient)	Hematologic	30213874

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPHB2 gene.

• not provided (43 variants)
• Inborn genetic diseases (27 variants)
• Prostate cancer/brain cancer susceptibility (2 variants)
• not specified (1 variants)
• Irido-corneo-trabecular dysgenesis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPHB2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				22	8	30
missense			28	4	2	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				2	3	5
Total	0	0	28	28	13

Variants in EPHB2

This is a list of pathogenic ClinVar variants found in the EPHB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-22784429-C-T		not specified	Uncertain significance (Mar 20, 2023)
1-22784435-G-A		not specified	Uncertain significance (Jan 26, 2022)
1-22784475-C-T			Likely benign (Sep 14, 2018)
1-22784505-C-A			Likely benign (Oct 23, 2018)
1-22784526-C-T			Likely benign (Mar 01, 2018)
1-22784544-G-A		EPHB2-related disorder	Likely benign (Aug 06, 2019)
1-22784609-A-G		not specified	Uncertain significance (Feb 06, 2023)
1-22784656-A-G		not specified	Uncertain significance (Jan 17, 2024)
1-22784658-G-A		not specified	Uncertain significance (May 03, 2023)
1-22784695-G-A		not specified	Uncertain significance (Apr 18, 2023)
1-22784767-C-T		not specified	Uncertain significance (Feb 15, 2023)
1-22784775-C-T		EPHB2-related disorder	Benign (Aug 13, 2019)
1-22784777-G-A		not specified	Uncertain significance (Sep 01, 2021)
1-22784812-G-A		not specified	Uncertain significance (Jun 22, 2021)
1-22784826-C-T			Likely benign (May 26, 2018)
1-22784830-G-A		not specified	Uncertain significance (Jun 23, 2023)
1-22784860-C-T			not provided (-)
1-22784889-G-A			Benign (Dec 31, 2019)
1-22784919-G-T		EPHB2-related disorder	Likely benign (Aug 13, 2019)
1-22784922-G-A			Benign (Dec 31, 2019)
1-22784938-A-G		not specified	Uncertain significance (Apr 18, 2023)
1-22784946-C-T			Likely benign (May 29, 2018)
1-22784955-G-A			Likely benign (Jun 01, 2022)
1-22784991-C-T			Likely benign (Aug 22, 2018)
1-22784997-C-T			Likely benign (May 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPHB2	protein_coding	protein_coding	ENST00000374632	16	204487

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000347	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	465	639	0.727	0.0000453	6501
Missense in Polyphen		154	254.92	0.60412		2558
Synonymous	0.0652	267	268	0.995	0.0000209	1948
Loss of Function	5.59	3	42.2	0.0710	0.00000202	479

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.000510	0.000508
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.0000547	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. {ECO:0000269|PubMed:15300251}.
• Pathway: Axon guidance - Homo sapiens (human);Regulation of Microtubule Cytoskeleton;NLR Proteins;Transcriptional activation by NRF2;Developmental Biology;Alpha6Beta4Integrin;EPH-Ephrin signaling;Ephrin signaling;EGFR1;Ephrin B reverse signaling;L1CAM interactions;Axon guidance;EPHB forward signaling;Syndecan-2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.580

Intolerance Scores

• loftool: 0.112
• rvis_EVS: -1.46
• rvis_percentile_EVS: 3.86

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.783
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.535

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ephb2
• Phenotype: renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: angiogenesis;urogenital system development;negative regulation of protein phosphorylation;transmembrane receptor protein tyrosine kinase signaling pathway;nervous system development;axon guidance;axonal fasciculation;learning or memory;learning;positive regulation of gene expression;phosphorylation;peptidyl-tyrosine phosphorylation;optic nerve morphogenesis;central nervous system projection neuron axonogenesis;corpus callosum development;retinal ganglion cell axon guidance;positive regulation of synaptic plasticity;inner ear morphogenesis;negative regulation of Ras protein signal transduction;ephrin receptor signaling pathway;regulation of neuronal synaptic plasticity;positive regulation of long-term neuronal synaptic plasticity;camera-type eye morphogenesis;negative regulation of axonogenesis;regulation of body fluid levels;inactivation of MAPKK activity;positive regulation of synapse assembly;roof of mouth development;dendritic spine development;dendritic spine morphogenesis;negative regulation of ERK1 and ERK2 cascade;commissural neuron axon guidance;postsynaptic membrane assembly;neuron projection retraction;positive regulation of long-term synaptic potentiation;positive regulation of protein localization to plasma membrane;negative regulation of NMDA glutamate receptor activity;positive regulation of NMDA glutamate receptor activity
• Cellular component: extracellular region;nucleus;cytosol;plasma membrane;integral component of plasma membrane;axon;dendrite;neuron projection;neuronal cell body;receptor complex;postsynapse;glutamatergic synapse;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: amyloid-beta binding;protein tyrosine kinase activity;transmembrane receptor protein tyrosine kinase activity;transmembrane-ephrin receptor activity;signaling receptor binding;protein binding;ATP binding;axon guidance receptor activity;identical protein binding;protein-containing complex binding