Bleeding and platelet disorders

Gene: TUBA4A

Comment on list classification: As reviewed by Carl Fratter, there is only one published human case of macrothrombocytopenia and functional evidence from mouse model reported in association with variants in TUBA4A gene. This gene has been classified with 'Limited' rating by the Hemostasis Thrombosis expert panel in ClinGen. This gene can therefore be rated amber with the current evidence.

Created: 13 May 2026, 11:30 a.m. | Last Modified: 13 May 2026, 11:30 a.m.

Panel Version: 4.11

I don't know

Reviewed by regional haemostasis genomics MDT and propose amber rating.
ClinGen Gene-Disease Validity for association with AD macrothrombocytopenia has been classified as “limited”.
PMID: 30760556 – heterozygous double missense variant detected in an individual with mild macrothrombocytopenia and tubulin disorganisation in platelets; evidence for TUBA4A association with macrothrombocytopenia supported by mouse model (different variant) and other functional work demonstrating that alpha4A-tubulin is the predominant alpha-tubulin in platelets and is essential for platelet biogenesis.
PMID: 36026602 – further work in mice demonstrating importance of alpha4A-tubulin in platelets.
Vincenot et al. 2024 report 2 further families in a meeting abstract but not yet published in a peer review journal.
Sources: NHS GMS

Created: 11 May 2026, 12:08 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Macrothrombocytopenia

Publications

• PMID: 30760556
• 36026602