EPHB4
Basic information
Region (hg38): 7:100802565-100827523
Previous symbols: [ "HTK" ]
Links
Phenotypes
GenCC
Source:
- capillary malformation-arteriovenous malformation 2 (Limited), mode of inheritance: AD
- capillary malformation-arteriovenous malformation 2 (Strong), mode of inheritance: AD
- capillary malformation-arteriovenous malformation 2 (Definitive), mode of inheritance: AD
- lymphatic malformation 7 (Limited), mode of inheritance: AD
- capillary malformation-arteriovenous malformation syndrome (Supportive), mode of inheritance: AD
- capillary malformation-arteriovenous malformation 2 (Strong), mode of inheritance: AD
- lymphatic malformation 7 (Strong), mode of inheritance: AD
- EPHB4-associated vascular malformation spectrum (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Capillary malformation-arteriovenous malformation 2 | AD | Cardiovascular | Life-threatening complications of arteriovenous malformations and arteriovenous fistulas can include bleeding, congestive heart failure, and/or neurologic consequences, and surveillance may allow early detection and medical/surgical management, which may decrease morbidity/mortality | Cardiovascular | 27400125; 28687708; 28730721; 29444212 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (36 variants)
- Capillary malformation-arteriovenous malformation 2 (7 variants)
- Cardiovascular phenotype (4 variants)
- Capillary malformation-arteriovenous malformation syndrome (2 variants)
- Hereditary lymphedema type I (1 variants)
- Lymphatic malformation 7 (1 variants)
- EPHB4-related disorder (1 variants)
- Arteriovenous malformation (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPHB4 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 | 183 | 192 | ||||
missense | 15 | 241 | 62 | 325 | ||
nonsense | 25 | 35 | ||||
start loss | 1 | |||||
frameshift | 20 | 10 | 31 | |||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 8 | |||||
splice region | 2 | 6 | 11 | 1 | 20 | |
non coding | 22 | 43 | 69 | |||
Total | 49 | 41 | 249 | 267 | 56 |
Highest pathogenic variant AF is 0.00000657
Variants in EPHB4
This is a list of pathogenic ClinVar variants found in the EPHB4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
7-100803321-GTC-G | Benign (May 26, 2021) | |||
7-100803456-G-A | EPHB4-related disorder | Likely benign (Nov 07, 2022) | ||
7-100803468-T-C | Cardiovascular phenotype | Uncertain significance (Apr 22, 2022) | ||
7-100803470-C-T | Cardiovascular phenotype | Benign/Likely benign (Mar 23, 2021) | ||
7-100803471-G-A | Cardiovascular phenotype | Uncertain significance (Mar 09, 2021) | ||
7-100803476-C-A | Cardiovascular phenotype | Benign (Dec 18, 2023) | ||
7-100803476-C-T | Cardiovascular phenotype | Likely benign (May 20, 2019) | ||
7-100803477-G-A | Cardiovascular phenotype • EPHB4-related disorder | Uncertain significance (Jun 08, 2023) | ||
7-100803477-G-C | Cardiovascular phenotype | Likely benign (Oct 03, 2022) | ||
7-100803494-C-T | Cardiovascular phenotype | Benign (Nov 27, 2023) | ||
7-100803495-G-A | Cardiovascular phenotype | Conflicting classifications of pathogenicity (Jan 29, 2024) | ||
7-100803502-C-T | Cardiovascular phenotype | Uncertain significance (Jul 12, 2021) | ||
7-100803503-C-T | Cardiovascular phenotype | Likely benign (Dec 08, 2019) | ||
7-100803509-G-A | Cardiovascular phenotype | Likely benign (May 11, 2023) | ||
7-100803510-G-T | EPHB4-associated vascular malformation spectrum | Uncertain significance (Jan 05, 2024) | ||
7-100803513-T-C | Cardiovascular phenotype | Uncertain significance (Jan 01, 2024) | ||
7-100803515-G-A | Cardiovascular phenotype | Likely benign (Jan 28, 2021) | ||
7-100803517-A-G | Cardiovascular phenotype | Uncertain significance (Oct 08, 2023) | ||
7-100803532-C-T | Cardiovascular phenotype | Likely benign (Apr 20, 2023) | ||
7-100803535-T-C | Cardiovascular phenotype | Uncertain significance (Oct 12, 2021) | ||
7-100803548-C-A | Cardiovascular phenotype | Uncertain significance (Jan 01, 2024) | ||
7-100803557-T-C | Cardiovascular phenotype | Likely benign (Mar 07, 2024) | ||
7-100803561-G-A | Benign/Likely benign (Jan 12, 2024) | |||
7-100803563-CAG-C | Lymphatic malformation 7 | Likely pathogenic (Apr 12, 2018) | ||
7-100803574-C-T | Cardiovascular phenotype | Uncertain significance (Jan 16, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
EPHB4 | protein_coding | protein_coding | ENST00000358173 | 17 | 24935 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.0135 | 0.987 | 125724 | 0 | 24 | 125748 | 0.0000954 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 2.30 | 475 | 638 | 0.744 | 0.0000437 | 6241 |
Missense in Polyphen | 178 | 301.11 | 0.59115 | 3021 | ||
Synonymous | -1.02 | 303 | 281 | 1.08 | 0.0000207 | 2073 |
Loss of Function | 4.87 | 14 | 51.8 | 0.270 | 0.00000308 | 500 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000294 | 0.000294 |
Ashkenazi Jewish | 0.000499 | 0.000496 |
East Asian | 0.0000545 | 0.0000544 |
Finnish | 0.000105 | 0.0000924 |
European (Non-Finnish) | 0.0000444 | 0.0000439 |
Middle Eastern | 0.0000545 | 0.0000544 |
South Asian | 0.0000327 | 0.0000327 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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. Together with its cognate ligand/functional ligand EFNB2 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 form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis. {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904, ECO:0000269|PubMed:27400125}.;
- Disease
- DISEASE: Hydrops fetalis, non-immune, and/or atrial septal defect (HFASD) [MIM:617300]: A form of non-immune hydrops fetalis, a condition characterized by fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are non-immune conditions that present with generalized edema of the fetus. Approximately 15% of non-immune cases result from a lymphatic abnormality. HFASD is an autosomal dominant, lymphatic-related form with variable expressivity. Some patients suffer from severe manifestations that can result in early death, whereas others have milder clinical features, such as atrial septal defect or varicose veins as adults. The hydrops and/or swelling improves spontaneously in those who survive the neonatal period. {ECO:0000269|PubMed:27400125}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
- Pathway
- Axon guidance - Homo sapiens (human);Vitamin D Receptor Pathway;Developmental Biology;EPH-Ephrin signaling;Ephrin signaling;EGFR1;Ephrin B reverse signaling;Axon guidance;EPHB forward signaling
(Consensus)
Recessive Scores
- pRec
- 0.258
Intolerance Scores
- loftool
- 0.274
- rvis_EVS
- -1.5
- rvis_percentile_EVS
- 3.6
Haploinsufficiency Scores
- pHI
- 0.469
- hipred
- Y
- hipred_score
- 0.694
- ghis
- 0.638
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.876
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ephb4
- Phenotype
- muscle phenotype; growth/size/body region phenotype; renal/urinary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); embryo phenotype;
Zebrafish Information Network
- Gene name
- ephb4b
- Affected structure
- heart tube
- Phenotype tag
- abnormal
- Phenotype quality
- decreased occurrence
Gene ontology
- Biological process
- angiogenesis;cell migration involved in sprouting angiogenesis;heart morphogenesis;cell adhesion;transmembrane receptor protein tyrosine kinase signaling pathway;axon guidance;peptidyl-tyrosine phosphorylation;protein autophosphorylation;ephrin receptor signaling pathway
- Cellular component
- extracellular region;cytosol;plasma membrane;integral component of plasma membrane;neuron projection;receptor complex;extracellular exosome
- Molecular function
- protein tyrosine kinase activity;transmembrane receptor protein tyrosine kinase activity;ephrin receptor activity;transmembrane-ephrin receptor activity;protein binding;ATP binding