Intellectual disability syndromic and non-syndromic
Gene: TAF4

TAF4 (TATA-box binding protein associated factor 4)
EnsemblGeneIds (GRCh38): ENSG00000130699
EnsemblGeneIds (GRCh37): ENSG00000130699
OMIM: 601796, Gene2Phenotype
TAF4 is in 2 panels

3 reviews

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Janssen et al (2022 - PMID: 35904126) describe the phenotype of 8 unrelated individuals with de novo pLoF TAF4 variants.

Overlapping features included speech delay (in 7/8), ID (7/8), behavioral abnormalities (6/8), joint laxity (4/8), spine anomalies (3/8), brain MRI abnrmalities (3/5). Mild non-specific/recognizable facial features were observed.

All 8 individuals were investigated with trio-ES/GS and harbored harbored de novo pLoF (nonsense / frameshift) TAF4 variants with no other SNVs/CNVs explaining their phenotype.

TAF4 encodes TATA-binding protein associated factor 4, a subunit of the transcription factor IID complex, which has a central role in transcription initiation.

TAF4 participates in the formation of a subcomplex with TAF12 (TAF4-TAF12 dimerization mediated by the C-terminal domain of TAF4), TAF5, TAF6 and TAF9. As the TFIID complex has 3 main lobes (A,B,C) with the TAF4/5/6/9/12 complex participating in A and B, TFIID contains 2 copies of TAF4.

In gnomAD TAF4 has a pLI score of 1, o/e : 0, LOEUF : 0.08.

Among the 8 different variants reported, 6 are expected to lead to NMD while 2 further localize in the last exon (15/15 - NM_003185.3) leading presumably to a truncated protein. This C-terminal domain is however important for TAF4-TAF12 dimerization essential for the TFIID complex.

Comparison with other disorders caused by mutation in genes encoding other TFIID complex members (incl. TAF1, TAF2, TAF6, TAF13) revealed that all TAF-opathies all share ID as a feature.
Created: 18 Aug 2022, 9:36 a.m. | Last Modified: 18 Aug 2022, 9:36 a.m.

Panel Version: 0.4895

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

Publications

35904126

Created: 18 Aug 2022, 9:36 a.m.
Last Modified: 18 Aug 2022, 9:36 a.m.
Panel version: 0.4895

Ee Ming Wong (Victorian Clinical Genetics Services)

Green List (high evidence)

PMIDs: 33875846; 28191890 - Three individuals reported with de novo LoF variants as part of large cohorts, limited phenotypic information available.

PMID: 35904126 - Additional eight unrelated individuals with neurodevelopmental disorder heterozygous for de novo loss-of-function variants in TAF4. Common features include intellectual disability, behavioural abnormalities, skeletal anomalies, and variable facial dysmorphologies.
Two frameshift variants not predicted to result in NMD are expected to disrupt the CCTD motif at the C‐terminus of TAF4 (known to facilitate the binding of TAF4 to TAF12).
Created: 11 Aug 2022, 6:54 a.m. | Last Modified: 11 Aug 2022, 6:54 a.m.

Panel Version: 0.4874

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder, MONDO:0700092, TAF4-related

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 11 Aug 2022, 6:54 a.m.
Last Modified: 11 Aug 2022, 6:54 a.m.
Panel version: 0.4874

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Three individuals reported with de novo LoF variants as part of large cohorts, limited phenotypic information available.
Sources: Literature
Created: 3 Dec 2021, 8:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder, autosomal dominant 73, MIM# 620450

Publications

Created: 3 Dec 2021, 8:23 p.m.

Panel version: 0.5294

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Literature

Phenotypes

Intellectual developmental disorder, autosomal dominant 73, MIM# 620450

OMIM

601796

Clinvar variants

Variants in TAF4

Penetrance

None

Publications

Panels with this gene