Genes in panel
STRs in panel
Prev Next
Regions in panel
Prev Next

Deafness_IsolatedAndComplex

Gene: TUBB4B

Green List (high evidence)

TUBB4B (tubulin beta 4B class IVb)
EnsemblGeneIds (GRCh38): ENSG00000188229
EnsemblGeneIds (GRCh37): ENSG00000188229
OMIM: 602660, Gene2Phenotype
TUBB4B is in 6 panels

3 reviews

Chirag Patel (Genetic Health Queensland)

Green List (high evidence)

ESHG 2023:
De novo heterozygous TUBB4B variants found in:
-8 patients with recurrent respiratory infections (PCD phenotype), irregular corpus callosum, and dilated ventricles (suggesting motile cilia anomaly)
-3 patients with retinal dystrophy, SNHL, and PCD respiratory issues

Functional studies:
-variants showed decreased cilia number and length, and mislocalisation of dyenin motors
-mouse models had decreased cilia number and length in trachea, and reduction in cilia in choroid plexus cells leading to hydrocephaly
Created: 25 Jul 2023, 2:22 a.m. | Last Modified: 25 Jul 2023, 2:22 a.m.
Panel Version: 1.157

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Primary ciliary dyskinesia

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Phenotypes
Leber congenital amaurosis with early-onset deafness, MIM# 617879

Lilian Downie (Victorian Clinical Genetics Services)

Green List (high evidence)

The TUBB4B gene has been associated with autosomal dominant Leber congenital amaurosis with early-onset deafness using the ClinGen Clinical Validity Framework as of 6/12/2018. This association was made using case-level data only. At least 2 missense variants have been reported de novo in humans, p.Arg391His and p.Arg391Cys. TUBB4B was first associated with this disease in humans in 2017 (Luscan et al.). Association is seen in at least 4 probands in 1 publication (29198720). Variants in this gene segregated with disease in 3 additional family members. This gene-disease association is supported by an in vitro functional assay. According to Luscan et al. 2017, the Arg391, Arg390 and Lys392 residues form a binding pocket that interacts with alpha-tubulin in the longitudinally adjacent tubulin alpha-beta-heterodimer. It is possible that a substitution at Arg391 destabilizes the hydrophobic interactions between the residues.
Created: 28 Jan 2020, 11:36 p.m. | Last Modified: 28 Jan 2020, 11:36 p.m.
Panel Version: 0.265

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Leber congenital amaurosis with early-onset deafness

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Melbourne Genomics Health Alliance Deafness Flagship
  • Victorian Clinical Genetics Services
Phenotypes
  • Leber congenital amaurosis with early-onset deafness, MIM# 617879
OMIM
602660
Clinvar variants
Variants in TUBB4B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Oct 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness to Leber congenital amaurosis with early-onset deafness, MIM# 617879

29 Jan 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: tubb4b has been classified as Green List (High Evidence).

29 Jan 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness to Leber congenital amaurosis with early-onset deafness

29 Jan 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness to Leber congenital amaurosis with early-onset deafness

29 Jan 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TUBB4B were changed from to Leber congenital amaurosis with early-onset deafness

29 Jan 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: TUBB4B were set to 29198720

29 Jan 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: TUBB4B were set to

29 Jan 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: TUBB4B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: TUBB4B was added gene: TUBB4B was added to Deafness_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Deafness Flagship Mode of inheritance for gene: TUBB4B was set to Unknown