Monogenic hearing loss
Gene: ATP11A
Comment on list classification: This gene should be rated GREEN as it has been implicated in sensorineural hearing loss from four unrelated families, and supported by functional studies from mouse model.Created: 23 Mar 2023, 4:42 p.m. | Last Modified: 23 Mar 2023, 4:42 p.m.
Panel Version: 4.3
A heterozygous cryptic donor splice site variant in ATP11A has been identified in a large 6-generation family from Newfoundland in which 16 individuals had progressive sensorineural hearing loss. In addition, several individuals with postlingual-onset progressive hearing loss from two unrelated multigenerational Jewish Israeli families with their origins in Uzbekistan and Afghanistan were also identified with a novel duplication in ATP11A (PMID:35278131).
5500 bp deletion involving the last coding exon of both ATP11A isoforms were identified in the large German multi-generational family that was first reported in PMID:28601886 with auditory synaptopathy/neuropathy, which is a distinct type of sensorineural hearing loss. The deletion is present in all affected individuals from the family and absent in two unaffected family members tested (PMID:36300302).
Functional studies in mice showed ATP11A protein is expressed in mouse inner ear and conditional Atp11a knockout mice showed age-progressive dysfunction or loss of spiral ganglion neurons, recapitulating the human phenotype of auditory neuropathy (PMID:36300302).
This gene has been associated with relevant phenotypes in OMIM, but not in Gene2Phenotype.
Sources: LiteratureCreated: 23 Mar 2023, 4:41 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Deafness, autosomal dominant 84, OMIM:619810
Publications
Gene: atp11a has been classified as Amber List (Moderate Evidence).
Tag Q1_23_promote_green tag was added to gene: ATP11A.
gene: ATP11A was added gene: ATP11A was added to Monogenic hearing loss. Sources: Literature Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP11A were set to 35278131; 36300302 Phenotypes for gene: ATP11A were set to Deafness, autosomal dominant 84, OMIM:619810 Review for gene: ATP11A was set to GREEN