EPHA2

EPH receptor A2, the group of EPH receptors|Sterile alpha motif domain containing

Basic information

Region (hg38): 1:16124337-16156069

Previous symbols: [ "ECK" ]

Links

ENSG00000142627 ∙ NCBI:1969 ∙ OMIM:176946 ∙ HGNC:3386 ∙ Uniprot:P29317 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• early-onset posterior polar cataract (Supportive), mode of inheritance: AD
• total early-onset cataract (Supportive), mode of inheritance: AD
• early-onset posterior subcapsular cataract (Supportive), mode of inheritance: AD
• cataract 6 multiple types (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 6, multiple types	AD	General	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	Ophthalmologic	19005574; 19649315; 20361013

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPHA2 gene.

• Cataract 6 multiple types (7 variants)
• not provided (2 variants)
• Cataract;Bilateral microphthalmos;Congenital aniridia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPHA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	35	22	65
missense		2	97	13	9	121
nonsense	2		1			3
start loss						0
frameshift	4		1			5
inframe indel						0
splice donor/acceptor (+/-2bp)	2	1	1			4
splice region			3	4	3	10
non coding	1		10	21	41	73
Total	9	3	118	69	72

Highest pathogenic variant AF is 0.0000131

Variants in EPHA2

This is a list of pathogenic ClinVar variants found in the EPHA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-16124370-C-T		Cataract 6 multiple types	Uncertain significance (Jan 13, 2018)
1-16124425-G-A		Cataract 6 multiple types	Uncertain significance (Jan 12, 2018)
1-16124473-A-T		Cataract 6 multiple types	Benign (Jan 13, 2018)
1-16124501-C-T		Cataract 6 multiple types	Benign (Jan 12, 2018)
1-16124547-C-A		Cataract 6 multiple types	Benign (Jan 13, 2018)
1-16124556-A-T		Cataract 6 multiple types	Benign (Jan 13, 2018)
1-16124590-C-T		Cataract 6 multiple types	Uncertain significance (Jan 13, 2018)
1-16124591-G-A		Cataract 6 multiple types	Uncertain significance (Jan 12, 2018)
1-16124672-G-A		Cataract 6 multiple types	Uncertain significance (Jan 13, 2018)
1-16124705-C-T		Cataract 6 multiple types	Benign (Jan 12, 2018)
1-16124772-A-G		Cataract 6 multiple types	Benign (Jan 12, 2018)
1-16124855-C-T		Cataract 6 multiple types	Benign (Jan 12, 2018)
1-16124860-T-C		Cataract 6 multiple types	Benign (Jan 13, 2018)
1-16124918-C-T		Cataract 6 multiple types	Benign (Jun 29, 2018)
1-16124931-G-A		Cataract 6 multiple types	Uncertain significance (Jan 13, 2018)
1-16124942-C-T		Cataract 6 multiple types	Uncertain significance (Jan 13, 2018)
1-16124991-C-A		Cataract 6 multiple types	Uncertain significance (Jan 13, 2018)
1-16125002-G-A		Cataract 6 multiple types	Benign (Jan 13, 2018)
1-16125049-C-T		Cataract 6 multiple types	Benign (Nov 10, 2018)
1-16125216-CAG-C		EPHA2-related disorder	Likely pathogenic (May 12, 2023)
1-16125227-C-T		Cataract 6 multiple types	Benign (Dec 20, 2023)
1-16125229-CCA-C		Cataract 6 multiple types	Pathogenic (Dec 30, 2019)
1-16125242-C-G		not specified • Cataract 6 multiple types • EPHA2-related disorder	Conflicting classifications of pathogenicity (Nov 28, 2023)
1-16125248-C-T		Cataract 6 multiple types	Likely benign (Jan 13, 2018)
1-16125254-TC-T			Pathogenic (Feb 01, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPHA2	protein_coding	protein_coding	ENST00000358432	17	31751

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000107	1.00	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	508	617	0.824	0.0000442	6343
Missense in Polyphen		175	258.77	0.67627		2632
Synonymous	-0.831	281	264	1.07	0.0000206	1945
Loss of Function	3.95	17	45.9	0.370	0.00000248	499

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000336	0.000333
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000339	0.000323
European (Non-Finnish)	0.000293	0.000290
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.000327	0.000326

dbNSFP

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}.
• Pathway: 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);Nuclear Receptors Meta-Pathway;NRF2 pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ras Signaling;Developmental Biology;EPH-Ephrin signaling;EGFR1;Direct p53 effectors;Axon guidance;Stabilization and expansion of the E-cadherin adherens junction;Arf6 signaling events;EPHA2 forward signaling;EPHA forward signaling (Consensus)

Recessive Scores

• pRec: 0.289

Intolerance Scores

• loftool: 0.473
• rvis_EVS: -0.63
• rvis_percentile_EVS: 16.82

Haploinsufficiency Scores

• pHI: 0.548
• hipred: Y
• hipred_score: 0.736
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Epha2
• Phenotype: homeostasis/metabolism phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; skeleton phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype

Gene ontology

• Biological process: skeletal system development;vasculogenesis;osteoblast differentiation;blood vessel endothelial cell proliferation involved in sprouting angiogenesis;inflammatory response;cell adhesion;transmembrane receptor protein tyrosine kinase signaling pathway;multicellular organism development;axon guidance;intrinsic apoptotic signaling pathway in response to DNA damage;regulation of lamellipodium assembly;notochord formation;cell migration;negative regulation of angiogenesis;peptidyl-tyrosine phosphorylation;neural tube development;neuron differentiation;keratinocyte differentiation;osteoclast differentiation;negative regulation of chemokine production;mammary gland epithelial cell proliferation;regulation of cell adhesion mediated by integrin;post-anal tail morphogenesis;protein kinase B signaling;regulation of blood vessel endothelial cell migration;regulation of angiogenesis;cAMP metabolic process;viral entry into host cell;bone remodeling;ephrin receptor signaling pathway;axial mesoderm formation;cell motility;defense response to Gram-positive bacterium;negative regulation of protein kinase B signaling;notochord cell development;cell chemotaxis;branching involved in mammary gland duct morphogenesis;lens fiber cell morphogenesis;regulation of ERK1 and ERK2 cascade;response to growth factor;protein localization to plasma membrane;activation of GTPase activity;negative regulation of lymphangiogenesis;positive regulation of protein localization to plasma membrane;positive regulation of bicellular tight junction assembly;pericyte cell differentiation
• Cellular component: plasma membrane;integral component of plasma membrane;focal adhesion;cell surface;lamellipodium;leading edge membrane;lamellipodium membrane;ruffle membrane;neuron projection;receptor complex;tight junction
• Molecular function: virus receptor activity;transmembrane receptor protein tyrosine kinase activity;transmembrane-ephrin receptor activity;protein binding;ATP binding;cadherin binding