Alternative titles; symbols
HGNC Approved Gene Symbol: TAF13
Cytogenetic location: 1p13.3 Genomic coordinates (GRCh38): 1:109,064,140-109,076,003 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p13.3 | Intellectual developmental disorder, autosomal recessive 60 | 617432 | Autosomal recessive | 3 |
The TAF13 gene is a constituent of at least 2 protein complexes, the TFIID complex and the small nuclear RNA gene- specific TAF complex (snTAFc), which play a critical role in the regulation of gene transcription in eukaryotic cells (summary by Tawamie et al., 2017).
Control of transcription by RNA polymerase II (see 180660) involves the basal transcription machinery, a collection of proteins which include TFIIB (TF2B; 189963), TFIIE (see 189962), TFIIF (see 189968), TBP (600075), TFIIA and TAFII250 (TAF2A; 313650). These, with RNA polymerase II, assemble into complexes which are modulated by transactivator proteins that bind to cis-regulatory elements located adjacent to the transcription start site. Some modulators interact directly with the basal complex, whereas others may act as bridging proteins linking transactivators to the basal transcription factors. Some of these associated factors are weakly attached while others are tightly associated with TBP in the TFIID complex. Among the latter are the TAF proteins. TAF components of the TFIID complex have been characterized from Drosophila cells and HeLa cells and many of the associated cDNAs have been cloned. Different TAFs are predicted to mediate the function of distinct transcriptional activators for a variety of gene promoters and RNA polymerases.
Mengus et al. (1995) designed degenerate oligonucleotide probes derived from the sequence of the purified TAFII18 subunit and used them to isolate a cDNA encoding a 124-amino acid protein of 16.5 kD, in agreement with the tryptic peptide sequences. They isolated the gene encoding TAF2K (also referred to as TAFII18), which was 28% identical to the yeast protein FUN 81 (whose function was unknown). The authors demonstrated that TAFII18 interacts through distinct domains with TBP, but that it interacts more strongly with TAFII28 (TAF11; 600772) and TAFII30 (TAF2H; 600475).
Crystal Structure
Birck et al. (1998) determined the crystal structure of the human TBP-associated factor TAFII28/TAFII18 heterodimer and showed that these TAFIIs form a novel histone-like pair in the TFIID complex. The histone folds in TAFII28 and TAFII18 were not predicted from their primary sequence, indicating that these TAFIIs define a novel family of atypical histone fold sequences.
The International Radiation Hybrid Mapping Consortium mapped the TAF13 (TAF2K) gene to chromosome 1 (SHGC-64750).
In 4 patients from 2 unrelated consanguineous families with autosomal recessive intellectual developmental disorder-60 (MRT60; 617432), Tawamie et al. (2017) identified homozygous missense mutations in the TAF13 gene (M40K, 600774.0001 and L31H, 600774.0002). The mutations, which were found by a combination of homozygosity mapping and exome sequencing, were confirmed by Sanger sequencing. The mutations segregated with the disorder in both families. Transfection of the mutations into HeLa cells showed that both mutant TAF13 proteins had decreased interaction with TAF11 (600772), thus impairing formation of the functional heterodimer. The M40K mutation had a more deleterious effect than the L31H mutation, which was consistent with the more severe phenotype in the patients with the M40K mutation. Knockdown of the TAF13 gene using siRNA in human neuroblastoma cells resulted in transcriptional dysregulation of genes involved in movement, migration, proliferation, morphology, protrusion formation, and differentiation. These changes affected neuron development and proliferation as well as neuritogenesis. Neuronal cells with knockdown of TAF13 showed increased proliferation and altered differentiation compared to controls. The findings highlighted the role of TAF13 in neuronal development.
In 2 sibs, born of consanguineous parents of Syrian Kurdish descent, with autosomal recessive mental retardation-60 (MRT60; 617432), Tawamie et al. (2017) identified a homozygous c.119T-A transversion (c.119T-A, NM_005645.3) in the TAF13 gene, resulting in a met40-to-lys (M40K) substitution at a highly conserved residue. The mutation, which was found by a combination of homozygosity mapping and exome sequencing, was confirmed by Sanger sequencing. The mutation segregated with the disorder in the family and was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases, in 380 Syrian control individuals, or in 728 in-house control exomes. Transfection of the mutation into HeLa cells showed that mutant TAF13 had decreased interaction with TAF11 (600772).
In 2 brothers, born of consanguineous parents of southern Italian descent, with autosomal recessive intellectual developmental disorder-60 (MRT60; 617432), Tawamie et al. (2017) identified a homozygous c.92T-A transversion (c.92T-A, NM_005645.3) in the TAF13 gene, resulting in a leu31-to-his (L31H) substitution at a highly conserved residue. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases, in 380 Syrian control individuals, or in 728 in-house control exomes. Transfection of the mutation into HeLa cells showed that mutant TAF13 had decreased interaction with TAF11 (600772).
Birck, C., Poch, O., Romier, C., Ruff, M., Mengus, G., Lavigne, A.-C., Davidson, I., Moras, D. Human TAFII28 and TAFII18 interact through a histone fold encoded by atypical evolutionary conserved motifs also found in the SPT3 family. Cell 94: 239-249, 1998. [PubMed: 9695952] [Full Text: https://doi.org/10.1016/s0092-8674(00)81423-3]
Mengus, G., May, M., Jacq, X., Staub, A., Tora, L., Chambon, P., Davidson, I. Cloning and characterization of hTAFII18, hTAFII20 and hTAFII28: three subunits of the human transcription factor TFIID. EMBO J. 14: 1520-1531, 1995. [PubMed: 7729427] [Full Text: https://doi.org/10.1002/j.1460-2075.1995.tb07138.x]
Tawamie, H., Martianov, I., Wohlfahrt, N., Buchert, R., Mengus, G., Uebe, S., Janiri, L., Hirsch, F. W., Schumacher, J., Ferrazzi, F., Sticht, H., Reis, A., Davidson, I., Colombo, R., Abou Jamra, R. Hypomorphic pathogenic variants in TAF13 are associated with autosomal-recessive intellectual disability and microcephaly. Am. J. Hum. Genet. 100: 555-561, 2017. [PubMed: 28257693] [Full Text: https://doi.org/10.1016/j.ajhg.2017.01.032]