CMT-TUBB3

Genetic Context

HGNC-Approved Gene Symbol

TUBB3

Gene Full Name

Tubulin Beta 3 Class III

Chromosome

16q24.3

Zygosity of Responsible Variant

Heterozygous

Variant Mechanism

Dominant-Negative

Details

Mechanistic basis:
Dominant-negative

Confidence:
Medium

Prediction:
The literature predicts a dominant-negative mechanism for CMT-TUBB3: heterozygous TUBB3 missense variants produce mutant β-tubulin that incorporates into the α/β-heterodimer and the microtubule lattice alongside wild-type, perturbing microtubule dynamics and kinesin interactions and impairing axonal transport, so supplementation is not predicted to rescue. There is no loss-of-function TUBB3 disease and no haploinsufficiency evidence, though some reports frame the altered microtubule behavior as a toxic gain of function, holding confidence at medium.

Rationale:
Mutant β-tubulin incorporates into the α/β-heterodimer and microtubule lattice alongside wild-type and disrupts the shared polymer, so wild-type supplementation is not predicted to rescue: a dominant-negative effect. Some reports read the altered kinesin behavior as a toxic gain of function, and that unsettled question holds confidence at medium.

ClinVar Pathogenic Variants

View CMT-TUBB3 ClinVar Variants

TUBB3 OMIM Entry

TUBB3 OMIM