EPHA7
protein-codingEPH receptor A7, the group of EPH receptors|Sterile alpha motif domain containing
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. Increased expression of this gene is associated with multiple forms of carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~179.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPHA7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004440.4. 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 | 2 | 1 | 4 | ||
| missense | 98 | 1 | 1 | 100 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 1 | 4 | |||
| Total | 0 | 0 | 104 | 4 | 2 | 110 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004431.1 | 17 | MANE Select | |
| Ensembl | ENSP00000358309.4 | 17 | MANE Select | |
| RefSeq | NP_001275558.1 | 17 | Standard | |
| RefSeq | NP_001275559.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Developmental Biology
- EPH-Ephrin signaling
- Axon guidance
- EPHA forward signaling
Biological Process
- apoptotic process
- transmembrane receptor protein tyrosine kinase signaling pathway
- axon guidance
- brain development
- phosphorylation
Molecular Function
- protein tyrosine kinase activity
- transmembrane receptor protein tyrosine kinase activity
- GPI-linked ephrin receptor activity
- transmembrane-ephrin receptor activity
- protein binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- dendrite
- neuromuscular junction
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369303
- Coding exons
- 17
- Length
- 179528
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125745
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.39 | 385 | 541 | 0.711 | 0.0000268 | 6560 |
| Missense (PolyPhen) | 134 | 221.84 | 0.60405 | 2739 | ||
| Synonymous | -0.384 | 193 | 186 | 1.04 | 0.00000946 | 1879 |
| Loss of Function | 6.24 | 2 | 49.3 | 0.0406 | 0.00000249 | 599 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI- anchored 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. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 AND MAPK3 which are phosphorylated upon activation of EPHA7. {ECO:0000269|PubMed:17726105}.;
Recessive Scores
- pRec
- 0.169
Intolerance Scores
- LoFtool
- 0.223
- RVIS EVS
- -0.86
- RVIS percentile EVS
- 10.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.952
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |