EPHA1
protein-codingEPH receptor A1, 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 is expressed in some human cancer cell lines and has been implicated in carcinogenesis. [provided by RefSeq, Jul 2008]
- EPHT
- EPHT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.6 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 EPHA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005232.5. 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 | 3 | 2 | 4 | 9 | ||
| missense | 170 | 11 | 181 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 180 | 13 | 4 | 197 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005223.4 | 18 | MANE Select | |
| Ensembl | ENSP00000275815.3 | 18 | MANE Select | |
| Ensembl | ENSP00000589390.1 | 18 | Standard | |
| Ensembl | ENSP00000589390.1 | 18 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
- Developmental Biology
- EPH-Ephrin signaling
- POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
Biological Process
- angiogenesis
- positive regulation of cell-matrix adhesion
- negative regulation of protein kinase activity
- cell surface receptor signaling pathway
- transmembrane receptor protein tyrosine kinase signaling pathway
Molecular Function
- protein kinase activity
- transmembrane receptor protein tyrosine kinase activity
- transmembrane-ephrin receptor activity
- ATP binding
- protein kinase binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- neuron projection
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000275815
- Coding exons
- 18
- Length
- 18604
- Individuals with no LoFs
- 125561
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 185
- Defined
- 125748
- p
- 0.000744
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.222 | 574 | 589 | 0.974 | 0.0000371 | 6266 |
| Missense (PolyPhen) | 222 | 254.71 | 0.87158 | 2811 | ||
| Synonymous | 0.0113 | 238 | 238 | 0.999 | 0.0000144 | 2055 |
| Loss of Function | 1.29 | 41 | 50.9 | 0.805 | 0.00000305 | 505 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00088 | 0.00080 | rare |
| Latino/Admixed American | 0.00069 | 0.00069 | rare |
| Ashkenazi Jewish | 0.0014 | 0.0014 | notable |
| East Asian | 0.00084 | 0.00082 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00081 | 0.00080 | rare |
| South Asian | 0.00062 | 0.00059 | rare |
| Other | 0.0015 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A 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. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Plays also a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis. {ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:19118217, ECO:0000269|PubMed:20043122}.;
Recessive Scores
- pRec
- 0.179
Intolerance Scores
- LoFtool
- 0.565
- RVIS EVS
- -0.9
- RVIS percentile EVS
- 10.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.712
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |