EPHA6
protein-codingEPH receptor A6, the group of EPH receptors|Sterile alpha motif domain containing
Gene summary
Predicted to enable transmembrane-ephrin receptor activity. Predicted to be involved in axon guidance and ephrin receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in dendrite and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~947.0 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 EPHA6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080448.3. 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 | 1 | 1 | 3 | ||
| missense | 128 | 2 | 1 | 131 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 129 | 3 | 2 | 134 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001073917.2 | 18 | MANE Select | |
| Ensembl | ENSP00000374323.5 | 18 | MANE Select | |
| RefSeq | NP_001265229.1 | 11 | Standard | |
| RefSeq | NP_001265230.1 | 4 | 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
- transmembrane receptor protein tyrosine kinase signaling pathway
- axon guidance
- biological_process
- peptidyl-tyrosine phosphorylation
- ephrin receptor signaling pathway
Molecular Function
- molecular_function
- transmembrane receptor protein tyrosine kinase activity
- transmembrane-ephrin receptor activity
- ATP binding
Cellular Component
- cellular_component
- nucleoplasm
- plasma membrane
- integral component of plasma membrane
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000389672
- Coding exons
- 18
- Length
- 937880
- Individuals with no LoFs
- 124726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 124746
- p
- 0.0000802
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.50 | 505 | 609 | 0.829 | 0.0000311 | 7408 |
| Missense (PolyPhen) | 185 | 288 | 0.64237 | 3444 | ||
| Synonymous | -1.11 | 233 | 212 | 1.10 | 0.0000108 | 2176 |
| Loss of Function | 5.05 | 10 | 47.5 | 0.210 | 0.00000252 | 614 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00021 | 0.00019 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00017 | rare |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000074 | 0.000071 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| 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 (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.440
- RVIS EVS
- -0.77
- RVIS percentile EVS
- 13.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.315
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |