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The gene TADA1 (HGNC:30631) has been recently implicated as a candidate for intellectual disability (MONDO_0001071) based on genomic findings from a large exome sequencing study of 337 individuals with intellectual disability (PMID:27431290). In this study, TADA1 was included among 32 potential candidates, predominantly identified via a recessive mode of inheritance. However, unlike other genes where multiple independent probands and clear pathogenic variants were reported, no explicit TADA1 variant meeting stringent HGVS criteria was provided. Furthermore, there is no segregation or detailed variant spectrum data (e.g., missense, LoF) uniquely ascribed to TADA1 in the available evidence. The absence of recurrent variants or functional analyses further limits the evidence supporting a definitive role of TADA1 in intellectual disability. As such, while its inclusion in the candidate gene list suggests a possible association, the overall genetic evidence for TADA1 remains modest.
The current evidence lacks functional validation or experimental studies (e.g., animal models, expression assays) to corroborate TADA1’s pathogenic mechanism, leaving its contribution to intellectual disability unconfirmed. Importantly, although the genomic approach in the study provided a high diagnostic yield overall, the role of TADA1 was not independently stratified from other genes with stronger supporting data. This limited level of evidence underscores the need for additional replication in independent cohorts, segregation analyses in affected families, and rigorous functional evaluation. In summary, while TADA1 emerges as an intriguing candidate gene for intellectual disability, clinicians and researchers should interpret its association with caution until further supporting studies are conducted.
Key Take‑home sentence: The emerging association of TADA1 with intellectual disability shows promise but currently remains limited in scope, necessitating further validation for robust clinical utility.
Gene–Disease AssociationLimitedTADA1 was identified among 32 candidate genes in a large exome sequencing study of intellectual disability (337 subjects) (PMID:27431290). However, the absence of recurrent variants, segregation data, or experimental confirmation limits the overall strength of this association. Genetic EvidenceLimitedNo explicit pathogenic variant in TADA1 meeting rigorous HGVS criteria was provided, and the candidate status relies solely on its inclusion in a broad panel with rare recessive variants. Functional EvidenceNoneThere are no functional assessment studies or experimental data offered in the supplied evidence to support a pathogenic mechanism for TADA1. |