EPHA3
protein-codingEPH receptor A3, the group of Sterile alpha motif domain containing|EPH receptors
Gene summary
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin 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. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]
- ETK
- ETK1
- TYRO4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~374.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPHA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005233.6. 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 | 7 | 3 | 11 | ||
| missense | 85 | 4 | 1 | 90 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 87 | 11 | 4 | 102 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005224.2 | 17 | MANE Select | |
| Ensembl | ENSP00000337451.2 | 17 | MANE Select | |
| RefSeq | NP_001397707.1 | 17 | Standard | |
| RefSeq | NP_872585.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Nuclear Receptors Meta-Pathway
- NRF2 pathway
- Developmental Biology
- EPH-Ephrin signaling
Biological Process
- cell adhesion
- transmembrane receptor protein tyrosine kinase signaling pathway
- axon guidance
- regulation of epithelial to mesenchymal transition
- positive regulation of neuron projection development
Molecular Function
- transmembrane receptor protein tyrosine kinase activity
- GPI-linked ephrin receptor activity
- transmembrane-ephrin receptor activity
- protein binding
- ATP binding
Cellular Component
- extracellular region
- early endosome
- plasma membrane
- integral component of plasma membrane
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336596
- Coding exons
- 17
- Length
- 374611
- Individuals with no LoFs
- 125716
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125748
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.652 | 503 | 546 | 0.921 | 0.0000281 | 6474 |
| Missense (PolyPhen) | 256 | 308.31 | 0.83033 | 3693 | ||
| Synonymous | -0.938 | 214 | 197 | 1.08 | 0.0000104 | 1878 |
| Loss of Function | 4.25 | 18 | 50.6 | 0.356 | 0.00000301 | 552 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin 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. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}.;
- Disease
- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12738854}. Note=The gene represented in this entry may be involved in disease pathogenesis.;
Recessive Scores
- pRec
- 0.212
Intolerance Scores
- LoFtool
- 0.291
- RVIS EVS
- -0.9
- RVIS percentile EVS
- 10.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.962
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | High | High |