ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

TUBB3 encodes a beta-tubulin class III protein that functions in the nervous system to regulate a variety of processes including microtubule dynamics, kinesin interactions and axon guidance. Heterozygous missense variants in TUBB3 have been identified in association with a spectrum of nervous system development phenotypes including hypoplasia of the oculomotor nerves and malformations of cortical development. Functional studies suggest a dominant effect of these mutations underlies pathogenicity of TUBB3-related phenotypes. There is currently insufficient evidence that deletion (haploinsufficiency) of TUBB3 is disease-causing. A report of non-focal deletion involving TUBB3 and additional genes is summarized below. Therefore the current haploinsufficiency score is 0. Additional relevant literature is summarized below: Gronborg et al. 2015 (PMID: 26109418) described monozygotic twins with a 320 kb de novo deletion of 16q24.3 which included the gene TUBB3 and 10 other genes. The phenotypic features included global developmental delay, secondary microcephaly, mild spastic diplegia and mild facial dysmorphism, but did not include cortical or other cerebral malformations commonly observed in TUBB3-related disorders. Tischfield et al., 2010 (PMID: 20074521) reported 8 novel heterozygous missense variants and performed functional studies that support a dominant-negative or gain-of-function effect leading to TUBB3 syndromes.

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