EYA1

EYA transcriptional coactivator and phosphatase 1, the group of EYA transcriptional coactivator and phosphatases

Basic information

Region (hg38): 8:71197432-71592025

Previous symbols: [ "BOR" ]

Links

ENSG00000104313 ∙ NCBI:2138 ∙ OMIM:601653 ∙ HGNC:3519 ∙ Uniprot:Q99502 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• branchiootic syndrome 1 (Strong), mode of inheritance: AD
• branchiootorenal syndrome 1 (Definitive), mode of inheritance: AD
• otofaciocervical syndrome 1 (Limited), mode of inheritance: AD
• branchiootorenal syndrome 1 (Strong), mode of inheritance: AD
• branchio-oto-renal syndrome (Supportive), mode of inheritance: AD
• branchiootic syndrome (Supportive), mode of inheritance: AD
• branchio-oto-renal syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Branchiootic syndrome 1; Branchiootorenal syndrome 1, with or without cataracts; Otofaciocervical syndrome 1	AD	Audiologic/Otolaryngologic; Renal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In BOR, surveillance and treatment/prophylaxis related to vesicoureteral reflux can be beneficial	Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic; Renal	9020840; 9359046; 10991693; 11409867; 12404110; 15146463; 16441263; 16691597; 18177466; 18220287; 20301554; 19206155
Individuals can have characteristic aural anomalies, but these may not be readily ascertained; In BOR, surveillance and treatment/prophylaxis related to renal manifestations can be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EYA1 gene.

• Melnick-Fraser syndrome (206 variants)
• not provided (165 variants)
• Otofaciocervical syndrome 1 (116 variants)
• Branchiootic syndrome 1 (113 variants)
• not specified (50 variants)
• Branchiootorenal syndrome 1 (31 variants)
• Branchiootic syndrome 1;Otofaciocervical syndrome 1;Branchiootorenal syndrome 1 (14 variants)
• Rare genetic deafness (14 variants)
• Inborn genetic diseases (12 variants)
• Branchiootorenal Spectrum Disorders (12 variants)
• EYA1-related condition (11 variants)
• Branchiootorenal syndrome 1;Otofaciocervical syndrome 1;Branchiootic syndrome 1 (8 variants)
• Branchiootic syndrome 1;Branchiootorenal syndrome 1;Otofaciocervical syndrome 1 (7 variants)
• Otofaciocervical syndrome 1;Branchiootic syndrome 1;Branchiootorenal syndrome 1 (5 variants)
• Branchiootorenal syndrome 1;Branchiootic syndrome 1;Otofaciocervical syndrome 1 (4 variants)
• Otofaciocervical syndrome 1;Branchiootorenal syndrome 1;Branchiootic syndrome 1 (3 variants)
• Hearing impairment (2 variants)
• Focal segmental glomerulosclerosis (1 variants)
• Developmental cataract (1 variants)
• Bilateral renal agenesis;Anhydramnios (1 variants)
• Branchiooculofacial syndrome (1 variants)
• Renal hypoplasia (1 variants)
• Branchiootorenal syndrome with cataract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EYA1 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			7	36	6	49
missense	1	9	88	8	3	109
nonsense	28	7				35
start loss						0
frameshift	35	6	1			42
inframe indel			1			1
splice donor/acceptor (+/-2bp)	15	10	1			26
splice region	3	2	14	6	2	27
non coding			47	49	48	144
Total	79	32	145	93	57

Highest pathogenic variant AF is 0.0000200

Variants in EYA1

This is a list of pathogenic ClinVar variants found in the EYA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-71197450-T-C		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Benign (Jan 12, 2018)
8-71197668-A-T		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Uncertain significance (Jan 12, 2018)
8-71197742-T-G		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Uncertain significance (Jan 12, 2018)
8-71197759-C-T		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Benign (Jan 13, 2018)
8-71197771-A-ATGAT		Otofaciocervical syndrome 1 • Branchiootorenal Spectrum Disorders	Likely benign (Jun 14, 2016)
8-71197779-T-C		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Uncertain significance (Jan 13, 2018)
8-71197797-A-C		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Uncertain significance (Jan 13, 2018)
8-71197811-G-A		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Uncertain significance (Jan 12, 2018)
8-71197949-C-T		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Uncertain significance (Jan 12, 2018)
8-71197964-G-GTTGT		Branchiootorenal Spectrum Disorders • Otofaciocervical syndrome 1	Uncertain significance (Jun 14, 2016)
8-71198016-A-G		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Benign (Jan 13, 2018)
8-71198030-C-T		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Benign (Jan 13, 2018)
8-71198043-T-C		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Uncertain significance (Jan 12, 2018)
8-71198056-G-T		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Uncertain significance (Jan 13, 2018)
8-71198065-C-T		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Uncertain significance (Jan 13, 2018)
8-71198077-G-A		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Benign (Jan 13, 2018)
8-71198111-C-T		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Uncertain significance (Jan 13, 2018)
8-71198117-TTAA-T		Otofaciocervical syndrome 1 • Branchiootorenal Spectrum Disorders	Likely benign (Jun 14, 2016)
8-71198118-T-G		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Benign (Jan 13, 2018)
8-71198201-A-ATTCT		Otofaciocervical syndrome 1 • Branchiootorenal Spectrum Disorders	Uncertain significance (Jun 14, 2016)
8-71198214-A-G		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Uncertain significance (Jan 13, 2018)
8-71198438-T-TA		Otofaciocervical syndrome 1 • Branchiootorenal Spectrum Disorders	Uncertain significance (Jun 14, 2016)
8-71198474-G-A		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Uncertain significance (Jan 13, 2018)
8-71198492-C-T		Branchiootic syndrome 1 • Otofaciocervical syndrome 1	Uncertain significance (Jan 13, 2018)
8-71198540-A-G		Otofaciocervical syndrome 1 • Branchiootic syndrome 1	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EYA1	protein_coding	protein_coding	ENST00000340726	16	164800

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.946	0.0541	125740	0	7	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	273	325	0.841	0.0000182	3845
Missense in Polyphen		113	139.95	0.80744		1713
Synonymous	0.0821	121	122	0.991	0.00000735	1153
Loss of Function	4.60	6	35.7	0.168	0.00000187	413

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (By similarity). Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. '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 (PubMed:19234442). Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis (By similarity). Has also phosphatase activity with proteins phosphorylated on Ser and Thr residues (in vitro) (By similarity). Required for normal embryonic development of the craniofacial and trunk skeleton, kidneys and ears (By similarity). Together with SIX1, it plays an important role in hypaxial muscle development; in this it is functionally redundant with EYA2 (By similarity). {ECO:0000250|UniProtKB:P97767, ECO:0000269|PubMed:19234442}.
• Disease: DISEASE: Branchiootorenal syndrome 1 (BOR1) [MIM:113650]: A syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations. {ECO:0000269|PubMed:10464653, ECO:0000269|PubMed:10655545, ECO:0000269|PubMed:10991693, ECO:0000269|PubMed:11558900, ECO:0000269|PubMed:21280147, ECO:0000269|PubMed:9361030}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Otofaciocervical syndrome 1 (OTFCS1) [MIM:166780]: A disorder characterized by facial dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability. {ECO:0000269|PubMed:11409867, ECO:0000269|PubMed:16441263}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Branchiootic syndrome 1 (BOS1) [MIM:602588]: A syndrome characterized by usually bilateral branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, and structural defects of the outer, middle or inner ear. Otic defects include malformed and hypoplastic pinnae, a narrowed external ear canal, bulbous internal auditory canal, stapes fixation, malformed and hypoplastic cochlea. Branchial and otic anomalies overlap with those seen in individuals with the branchiootorenal syndrome. However renal anomalies are absent in branchiootic syndrome patients. {ECO:0000269|PubMed:12701758, ECO:0000269|PubMed:16691597, ECO:0000269|PubMed:9359046}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Anterior segment anomalies with or without cataract (ASA) [MIM:602588]: A disease characterized by various types of developmental eye anomalies, in the absence of other abnormalities. The phenotypic spectrum of anterior segment anomalies include central corneal opacity, Peters anomaly, and bilateral persistence of the pupillary membrane. Some patients have cataract. {ECO:0000269|PubMed:10655545}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human);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: 0.276

Intolerance Scores

• loftool: 0.0120
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.18

Haploinsufficiency Scores

• pHI: 0.827
• hipred: Y
• hipred_score: 0.653
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.931

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eya1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; reproductive system 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); normal 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); hematopoietic system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; 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); digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: eya1
• Affected structure: hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: metanephros development;branching involved in ureteric bud morphogenesis;outflow tract morphogenesis;double-strand break repair;pattern specification process;mesodermal cell fate specification;sensory perception of sound;anatomical structure morphogenesis;response to ionizing radiation;striated muscle tissue development;histone dephosphorylation;protein sumoylation;peptidyl-tyrosine dephosphorylation;aorta morphogenesis;outer ear morphogenesis;middle ear morphogenesis;regulation of neuron differentiation;positive regulation of DNA repair;positive regulation of transcription by RNA polymerase II;neuron fate specification;embryonic skeletal system morphogenesis;semicircular canal morphogenesis;anatomical structure development;positive regulation of epithelial cell proliferation;pharyngeal system development;otic vesicle morphogenesis;positive regulation of secondary heart field cardioblast proliferation;cochlea morphogenesis;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear body;protein-DNA complex
• Molecular function: RNA binding;protein tyrosine phosphatase activity;protein binding;metal ion binding