ClinGen Dosage Sensitivity Curation Page

TUBA1A

  • Curation Status: Complete

Location Information

Select assembly: (NC_000012.11) (NC_000012.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

PMID: 23033978: 100 patients with intellectual disability were analyzed by WES. In the series, a child with moderate ID, microcephaly, hypoplastic corpus callosum and vermis cerebelli, delayed myelination was found to have a de novo, frameshift mutation in TUBA1A. However, contrary to this, a previous large study of lissencephaly and lissencephaly/cerebellar hypoplasia patients found only de novo missense mutations (PMID: 20466733). As well, the authors reported that no TUBA1A deletions were detected in an ID population of ~15,000 patients (Signature Genomics data). The authors argued against haploinsufficiency for these reasons and suggested that the main mechanism of pathogenicity for this gene is likely a dominant negative effect, possibly disrupting tubulin-MAP interactions. However, the authors did not rule out the possibility that null mutations could be embryonic lethal.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity