Respiratory ciliopathies including non-CF bronchiectasis

Gene: TUBB4B

Green List (high evidence)

TUBB4B (tubulin beta 4B class IVb)
EnsemblGeneIds (GRCh38): ENSG00000188229
EnsemblGeneIds (GRCh37): ENSG00000188229
OMIM: 602660, Gene2Phenotype
TUBB4B is in 3 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 11 Dec 2025, 4:33 p.m. | Last Modified: 11 Dec 2025, 4:33 p.m.
Panel Version: 4.50

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The ClinGen Motile Ciliopathy expert panel has classified the association of TUBB4B gene to TUBB4B-related ciliopathy (MONDO:1060115) as 'Definitive'. More information can be found in https://search.clinicalgenome.org/CCID:006481.
Created: 17 Jul 2025, 1:51 p.m. | Last Modified: 17 Jul 2025, 1:51 p.m.
Panel Version: 4.41
Comment on list classification: There is sufficient evidence available (>10 unrelated cases and functional work) for the promotion of this gene to green rating on the next GMS update.
Created: 9 Jan 2025, 11:01 a.m. | Last Modified: 9 Jan 2025, 11:01 a.m.
Panel Version: 3.25
PMID:38662826 reported a cohort of 12 patients with primary ciliary dyskinesia (PCD) and with heterozygous variants in TUBB4B gene. Four different variants were reported in these patients. Common clinical features of airway disease including chronic wet cough (7/12), recurrent infections (11/12), bronchiectasis (8/12) and rhinosinusitis (9/12) were observed across the cohort/ 6/12 patients were reported with hydrocephaly. Four patients with the p.Pro358Ser variant also presented with Leber congenital amaurosis (LCA) associated with sensorineural hearing loss (SNHL). Similar cellular phenotype was also observed in patient-derived respiratory epithelial cells.

PMID:39115449 reported eight patients with PCD, of which one patient was identified with a de novo variant in TUBB4B gene. This patient presented with airways disease and hearing loss.

The PCD phenotype has not yet been reported in OMIM, while LCA phenotype is already associated with TUBB4B in OMIM (MIM #617879).
Sources: Literature
Created: 9 Jan 2025, 11 a.m. | Last Modified: 9 Jan 2025, 11:10 a.m.
Panel Version: 3.25

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
primary ciliary dyskinesia, MONDO:0016575

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
  • Literature
Phenotypes
  • primary ciliary dyskinesia, MONDO:0016575
OMIM
602660
Clinvar variants
Variants in TUBB4B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

11 Dec 2025, Gel status: 3

Removed Tag, Removed Tag

Eleanor Williams (Genomics England Curator)

Tag dd_review was removed from gene: TUBB4B. Tag Q1_25_ promote_green was removed from gene: TUBB4B.

11 Dec 2025, Gel status: 3

Added New Source, Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to TUBB4B. Source Expert Review Green was added to TUBB4B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

9 Jan 2025, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: tubb4b has been classified as Amber List (Moderate Evidence).

9 Jan 2025, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

gene: TUBB4B was added gene: TUBB4B was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Literature dd_review, Q1_25_ promote_green tags were added to gene: TUBB4B. Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TUBB4B were set to 38662826; 39115449 Phenotypes for gene: TUBB4B were set to primary ciliary dyskinesia, MONDO:0016575 Review for gene: TUBB4B was set to GREEN