EYA3

EYA transcriptional coactivator and phosphatase 3, the group of EYA transcriptional coactivator and phosphatases

Basic information

Region (hg38): 1:27970344-28088637

Links

ENSG00000158161 ∙ NCBI:2140 ∙ OMIM:601655 ∙ HGNC:3521 ∙ Uniprot:Q99504 ∙ 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 EYA3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EYA3 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						0
missense			27			27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	27	0	1

Variants in EYA3

This is a list of pathogenic ClinVar variants found in the EYA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-27974503-A-G		not specified	Uncertain significance (Jan 23, 2023)
1-27978424-T-A		not specified	Uncertain significance (Feb 13, 2025)
1-27978465-C-G		not specified	Uncertain significance (Apr 22, 2022)
1-27989727-G-A		not specified	Uncertain significance (Jan 04, 2025)
1-27989742-G-A		not specified	Uncertain significance (Jul 13, 2022)
1-27993444-C-T		not specified	Uncertain significance (Apr 19, 2023)
1-27993504-C-T		not specified	Uncertain significance (Dec 07, 2021)
1-27999970-T-C			Uncertain significance (May 04, 2022)
1-28000037-C-G		not specified	Uncertain significance (Sep 26, 2024)
1-28000058-C-T			Benign (Dec 31, 2018)
1-28004412-A-T		not specified	Uncertain significance (Jun 07, 2024)
1-28010996-C-T		not specified	Uncertain significance (Feb 10, 2022)
1-28011035-G-C		not specified	Uncertain significance (Apr 19, 2024)
1-28011065-G-A		not specified	Uncertain significance (Jan 24, 2025)
1-28011083-T-A		not specified	Uncertain significance (Aug 12, 2021)
1-28011084-C-A		not specified	Uncertain significance (Feb 13, 2025)
1-28013121-T-A		not specified	Uncertain significance (Jan 18, 2023)
1-28013143-G-A		not specified	Likely benign (Feb 07, 2025)
1-28013164-G-A		not specified	Uncertain significance (Mar 07, 2025)
1-28013189-T-C		not specified	Uncertain significance (Feb 27, 2024)
1-28013195-T-C		not specified	Uncertain significance (Sep 24, 2024)
1-28013219-C-T		not specified	Uncertain significance (Oct 21, 2024)
1-28013221-G-A		not specified	Uncertain significance (Apr 04, 2024)
1-28013266-T-C		not specified	Uncertain significance (Mar 30, 2024)
1-28017179-G-A		not specified	Uncertain significance (Dec 03, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EYA3	protein_coding	protein_coding	ENST00000373871	17	118353

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00298	125718	1	24	125743	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	205	299	0.685	0.0000141	3729
Missense in Polyphen		68	116.73	0.58253		1494
Synonymous	0.693	97	106	0.914	0.00000513	1096
Loss of Function	4.83	4	34.7	0.115	0.00000157	432

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000786	0.000786
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000114	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.000114	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye. {ECO:0000250|UniProtKB:P97480, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19351884}.
• Pathway: DNA Repair;DNA Double-Strand Break Repair;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response (Consensus)

Recessive Scores

• pRec: 0.0783

Intolerance Scores

• loftool: 0.237
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.883
• hipred: Y
• hipred_score: 0.728
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eya3
• Phenotype: skeleton 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: double-strand break repair;multicellular organism development;visual perception;anatomical structure morphogenesis;response to ionizing radiation;histone dephosphorylation;peptidyl-tyrosine dephosphorylation;positive regulation of DNA repair;anatomical structure development;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytoplasm;centrosome
• Molecular function: protein tyrosine phosphatase activity;protein binding;metal ion binding