EYA1

Gene Facts

• HGNC Symbol: EYA1 (HGNC:3519)
• HGNC Name: EYA transcriptional coactivator and phosphatase 1
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: BOR
• Alias symbols: No aliases found
• %HI: 1.33
• pLI: 1
• LOEUF: 0.29
• Cytoband: 8q13.3
• Genomic Coordinates:

  GRCh37/hg19:	chr8:72109668-72460329
  GRCh38/hg38:	chr8:71197433-71548094

• MANE Select Transcript: NM_000503.6 ENST00000340726.8
• 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... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-10850
• ClinGen Curation ID: CCID:007099
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Sufficient Evidence for Haploinsufficiency (3)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 08/26/2020

Haploinsufficiency (HI) Score Details

• HI Score: 3
• HI Evidence Strength: Sufficient Evidence for Haploinsufficiency

HI Disease

• branchiootorenal syndrome 1

HI Evidence

• PUBMED: 30086703
  In 2018, Wang et al. used PCR and Sanger sequencing on a family with Branchio-oto-renal (BOR) syndrome to identify potential variants in EYA1. Analysis identified a nonsense variant (p. Arg323X) in EYA1 in the proband and 3 affected family members. Of note, this variant was not present in the unaffected family members.
• PUBMED: 16813606
  In 2006, Clarke et al. used PCR on a family with Branchio-oto-renal (BOR) syndrome and Branchiootic (BO) syndrome to identify potential variants in EYA1. Analysis identified a variant resulting in a premature stop codon and potential protein truncation in the affected father and son. Of note, the father also had a child with bilaterally absent kidneys who is deceased, and thus was not available for this study. Testing revealed that the variant was de novo to the father, as it was not present in his parents. The variant was absent in all unaffected family members. Additionally, a missense variant was also identified in 1 of the affected individuals, but this variant was also present in unaffected family members.
• PUBMED: 29552445
  In 2018, Lie et al. used PCR and direct sequencing on an individual with Branchio-oto-renal (BOR) syndrome to investigate EYA1. Analysis identified a frameshift variant (p.R461fs467X) in EYA1 which leads to protein truncation. This variant was de novo, as it was not present in the proband’s unaffected parents.

• HI Evidence Comments: Large number of nonsense, frameshift, missense mutations reported. Intragenic deletions also reported. Please see GeneReviews for a detailed discussion. Additional references: PMID: 17637804 In 2007, Sanggaard et al. used marker analysis, linkage analysis, multiplex ligation-dependent analysis (MLPA), PCR, and sequencing on 6 families presenting with Branchio-oto-renal (BOR) syndrome to identify potential variants in SIX5, SIX1, and EYA1. In family 1, a nonsense variant (c.1773C>G) in EYA1 was identified in the 3 affected family members and absent in the unaffected family members. In family 6, a frameshift variant (c.920delG) leading to a premature stop codon was identified in the 2 affected family members available for testing. This variant was absent from the unaffected family members. PMID: 16491411 In 2005, Okada et al. used PCR and direct sequencing on 15 patients with Branchio-oto-renal (BOR) syndrome to identify variants in EYA1 and SIX1. Authors identified 4 patients with nonsense or splicing variants in EYA1. Patient 1 had a de novo nonsense variant and patient 2 had a nonsense variant of unknown inheritance. Patient 3 and his affected mother and sibling had a splicing variant in the gene, and patient 4 had a splicing variant of unknown inheritance. PMID: 17049623 In 2006, Lee et al. used PCR and direct sequencing on a Korean family with Branchio-oto-renal (BOR) syndrome to investigate EYA1. Analysis identified a nonsense variant (p.Gln144Ter) in the proband and their 4 affected family members. This variant was absent in unaffected family members. PMID: 19667416 In 2009, Lee et al. used PCR on a family with Branchio-oto-renal (BOR) syndrome. Analysis identified a frameshift variant (p.Ala107fs) resulting in protein truncation in the proband and his affected father.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity