GeneBe

EPHA2

protein-coding

EPH receptor A2, 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. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]

Previous symbols:
  • ECK

MANE transcript

NM_004431.5

Inheritance

AD, AR

ClinVar variants

P:23U:246B:116

Top phenotype

Cataract 6, multiple types

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr1:16,124,337-16,156,069

External References & Databases

Ensembl (ENSG00000142627)NCBI Gene (1969)OMIM (176946)HGNC:3386GenCCUniProt (P29317)AlphaFoldClinVar (EPHA2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~31.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

early-onset posterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020378

Submitter: Orphanet

cataract 6 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007288

Submitter: PanelApp Australia

cataract 6 multiple typesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007288

Submitter: Ambry Genetics

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

cataract 6 multiple typesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007288

Submitter: G2P

early-onset posterior subcapsular cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018610

Submitter: Orphanet

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

early-onset non-syndromic cataractMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011060

Submitter: Ambry Genetics

eye disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0005328

Submitter: PanelApp Australia

cataract 6 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007288

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Cataract 6, multiple typesAD

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 19005574; 19649315; 20361013Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EPHA2 variants in ClinVar

14 Conditions Cataloged
Cataract 6 multiple typesTotal: 201
Inborn genetic diseasesTotal: 143
not providedTotal: 101
EPHA2-related disorderTotal: 64
not specifiedTotal: 28
EPHA2-related disordersTotal: 6
Meniere diseaseTotal: 3
Bilateral microphthalmosTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004431.5. 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.

EffectPLPVUSLBBSum
synonymous
10
clinvar
62
clinvar
16
clinvar
 88
missense
2
clinvar
3
clinvar
224
clinvar
32
clinvar
6
clinvar
 267
nonsense
2
clinvar
2
clinvar
1
clinvar
 5
start loss
1
clinvar
 1
frameshift
5
clinvar
3
clinvar
2
clinvar
 10
splice donor/acceptor (+/-2bp)
2
clinvar
3
clinvar
9
clinvar
 14
Total11122469422385

Highest pathogenic variant AF is 0.000014910203

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004431.5RefSeqNP_004422.217MANE Select
ENST00000358432.8EnsemblENSP00000351209.517MANE Select
NM_001329090.2RefSeqNP_001316019.115Standard
ENST00000863593.1EnsemblENSP00000533652.117Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • PI3K-Akt signaling pathway - Homo sapiens (human)
  • Axon guidance - Homo sapiens (human)
  • Rap1 signaling pathway - Homo sapiens (human)
  • Ras signaling pathway - Homo sapiens (human)
  • MAPK signaling pathway - Homo sapiens (human)

Biological Process

  • skeletal system development
  • vasculogenesis
  • osteoblast differentiation
  • blood vessel endothelial cell proliferation involved in sprouting angiogenesis
  • inflammatory response

Molecular Function

  • virus receptor activity
  • transmembrane receptor protein tyrosine kinase activity
  • transmembrane-ephrin receptor activity
  • protein binding
  • ATP binding

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • focal adhesion
  • cell surface
  • lamellipodium

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000358432
Coding exons
17
Length
31751
Individuals with no LoFs
125695
Homozygous LoFs
0
Heterozygous LoFs
53
Defined
125748
p
0.000211
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.565086170.8240.00004426343
Missense (PolyPhen)175258.770.676272632
Synonymous-0.8312812641.070.00002061945
Loss of Function3.951745.90.3700.00000248499

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.000340.00032rare
European (Non-Finnish)0.000290.00029rare
South Asian0.000130.00013rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand- independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.;
Disease
DISEASE: Cataract 6, multiple types (CTRCT6) [MIM:116600]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT6 includes posterior polar and age- related cortical cataracts, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Age-related cortical cataract is a developmental punctate opacity restricted to the cortex. The cataract is white or cerulean, increases in number with age, but rarely affects vision. {ECO:0000269|PubMed:19005574, ECO:0000269|PubMed:19306328, ECO:0000269|PubMed:19649315, ECO:0000269|PubMed:22570727}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Overexpressed in several cancer types and promotes malignancy. {ECO:0000269|PubMed:19573808}.;

Recessive Scores

pRec
0.289

Intolerance Scores

LoFtool
0.473
RVIS EVS
-0.63
RVIS percentile EVS
16.82

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.757

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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