EPHA3

EPH receptor A3, the group of Sterile alpha motif domain containing|EPH receptors

Basic information

Region (hg38): 3:89107620-89482134

Previous symbols: [ "ETK", "ETK1", "TYRO4" ]

Links

ENSG00000044524 ∙ NCBI:2042 ∙ OMIM:179611 ∙ HGNC:3387 ∙ Uniprot:P29320 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPHA3 gene.

• Inborn genetic diseases (17 variants)
• not provided (6 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPHA3 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				2	2	4
missense			18	1	1	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	3	3

Variants in EPHA3

This is a list of pathogenic ClinVar variants found in the EPHA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-89107797-G-C		not specified	Uncertain significance (Nov 30, 2022)
3-89107820-G-T		EPHA3-related disorder	Likely benign (Apr 10, 2019)
3-89127255-C-G		not specified	Uncertain significance (Jan 20, 2023)
3-89210044-T-C		not specified	Uncertain significance (Jan 02, 2024)
3-89210274-G-A		not specified	Uncertain significance (Apr 12, 2023)
3-89210337-A-G		not specified	Uncertain significance (Feb 11, 2022)
3-89210404-A-G		not specified	Uncertain significance (Jul 15, 2021)
3-89210450-C-T		EPHA3-related disorder	Benign (May 28, 2019)
3-89340942-T-C		EPHA3-related disorder	Likely benign (May 02, 2019)
3-89340993-G-C		EPHA3-related disorder	Likely benign (Feb 15, 2023)
3-89341020-G-A		not specified	Uncertain significance (Jun 13, 2023)
3-89341874-A-C		not specified	Uncertain significance (Jan 10, 2023)
3-89341914-G-A		not specified	Uncertain significance (Dec 20, 2023)
3-89342064-C-T		not specified	Uncertain significance (Oct 25, 2023)
3-89342065-G-A		EPHA3-related disorder	Benign/Likely benign (Feb 01, 2023)
3-89395855-C-T		not specified	Uncertain significance (Sep 16, 2021)
3-89395941-G-C		not specified	Uncertain significance (Jan 23, 2024)
3-89399311-C-T		EPHA3-related disorder	Likely benign (Jun 21, 2019)
3-89399460-A-T		not specified	Uncertain significance (Dec 22, 2023)
3-89407300-G-A		EPHA3-related disorder	Likely benign (Oct 28, 2019)
3-89407322-G-C		not specified	Uncertain significance (Jul 13, 2021)
3-89407365-T-C		not specified	Uncertain significance (May 25, 2022)
3-89408126-G-A		not specified	Uncertain significance (Dec 15, 2023)
3-89413146-C-T		not specified	Uncertain significance (Sep 29, 2023)
3-89413153-G-A		not specified	Uncertain significance (Jan 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPHA3	protein_coding	protein_coding	ENST00000336596	17	374611

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000120	1.00	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.652	503	546	0.921	0.0000281	6474
Missense in Polyphen		256	308.31	0.83033		3693
Synonymous	-0.938	214	197	1.08	0.0000104	1878
Loss of Function	4.25	18	50.6	0.356	0.00000301	552

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000428	0.000427
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.000136	0.000131
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin 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. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}.
• Disease: DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12738854}. Note=The gene represented in this entry may be involved in disease pathogenesis.
• Pathway: Axon guidance - Homo sapiens (human);Nuclear Receptors Meta-Pathway;NRF2 pathway;Developmental Biology;EPH-Ephrin signaling;TCR;Axon guidance;EPHA forward signaling (Consensus)

Recessive Scores

• pRec: 0.212

Intolerance Scores

• loftool: 0.291
• rvis_EVS: -0.9
• rvis_percentile_EVS: 10.14

Haploinsufficiency Scores

• pHI: 0.299
• hipred: Y
• hipred_score: 0.747
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Epha3
• Phenotype: homeostasis/metabolism phenotype; 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); 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); liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cell adhesion;transmembrane receptor protein tyrosine kinase signaling pathway;axon guidance;regulation of epithelial to mesenchymal transition;positive regulation of neuron projection development;cell migration;peptidyl-tyrosine phosphorylation;regulation of actin cytoskeleton organization;regulation of GTPase activity;negative regulation of endocytosis;ephrin receptor signaling pathway;regulation of focal adhesion assembly;regulation of microtubule cytoskeleton organization;cellular response to retinoic acid;fasciculation of sensory neuron axon;fasciculation of motor neuron axon;positive regulation of protein localization to plasma membrane
• Cellular component: extracellular region;early endosome;plasma membrane;integral component of plasma membrane;neuron projection;receptor complex
• Molecular function: transmembrane receptor protein tyrosine kinase activity;GPI-linked ephrin receptor activity;transmembrane-ephrin receptor activity;protein binding;ATP binding