Alternative titles; symbols
HGNC Approved Gene Symbol: GTF2H2
Cytogenetic location: 5q13.2 Genomic coordinates (GRCh38): 5:71,035,347-71,067,676 (from NCBI)
Transcription factor IIH (TFIIH; see 189972) is associated with the RNA polymerase II transcription complex, which is involved in transcription and transcription-mediated DNA repair. Humbert et al. (1994) described the cloning of the genes encoding the human 44-kD subunit and the 34-kD subunit (601750) of TFIIH. The 44-kD subunit gene (also symbolized GTF2H2) appears to be the human counterpart of yeast SSL1, a gene involved in UV resistance.
The Rift Valley fever virus (RVFV) is the causative agent of fatal hemorrhagic fever in humans and acute hepatitis in ruminants. Le May et al. (2004) found that infection by RVFV led to a rapid and drastic suppression of host cellular RNA synthesis that paralleled a decrease of the TFIIH transcription factor cellular concentration. The nonstructural viral NSs protein interacted with the p44 component of TFIIH to form nuclear filamentous structures that also contained the XPB subunit of TFIIH (ERCC3; 133510). By competing with XPD (ERCC2; 126340), the natural partner of p44 within TFIIH, and sequestering p44 and XPB subunits, NSs prevented the assembly of TFIIH subunits, thus destabilizing the normal host cell life. These observations shed light on the mechanism utilized by RVFV to evade the host response.
The GTF2H2 gene maps to chromosome 5q12.2-q13.3 (van der Steege et al., 1995).
The childhood-onset spinal muscular atrophies are a clinical heterogeneous group of autosomal recessive disorders characterized by selective degeneration of the anterior horn cells with subsequent weakness and atrophy of limb muscles; see SMA1 (253300). The disease locus maps to 5q13, a region characterized by genetic instability and DNA duplication. Carter et al. (1997) noted that, among the duplicated genes in this region, the telomeric copy of the SMN (survival motor neuron) gene (SMN1; 600354) is thought to be the major disease-determining gene, since it is missing in the majority of SMA patients and since small, intragenic mutations in the gene have been associated with the disorder. Approximately half of the severely affected SMA1 patients are also missing both homologs of a neighboring gene, the neuronal apoptosis inhibitory protein (NAIP; 600355). The loss of NAIP may affect disease severity. Clearly, the molecular event underlying the childhood-onset SMAs are complex, possibly involving multiple genes. Carter et al. (1997) reported a third multicopy gene in the SMA region, encoding the p44 subunit of basal transcription factor II (BTF2). One copy of this transcription-repair gene (symbolized BTF2p44 by them) was deleted in at least 15% of all SMA cases. A single copy of the gene was mapped to the SMA region on 5q by van der Steege et al. (1995). Carter et al. (1997) reported the presence of multiple copies of the gene in the SMA region located in close proximity to NAIP and SMN1. Furthermore, they reported a 1-bp polymorphism that distinguished 2 gene copies and they documented the SMA-associated deletion of 1 version of the gene. The 2 polymorphic forms of the p44 gene differ by 2 nonconservative changes (ile-to-met in exon 7 and leu-to-val in exon 10), appear to be ubiquitously expressed, and are present in fetal and adult tissues and in SMA and control lymphoblasts. Carter et al. (1997) stated that physical mapping in the SMA region is complicated and imprecise, presumably due to the great instability and variability arising from the duplication, deletion, and gene conversion of highly homologous DNA in this region.
Carter, T. A., Bonnemann, C. G., Wang, C. H., Obici, S., Parano, E., De Fatima Bonaldo, M., Ross, B. M., Penchaszadeh, G. K., Mackenzie, A., Bento Soares, M., Kunkel, L. M., Gilliam, T. C. A multicopy transcription-repair gene, BTF2p44, maps to the SMA region and demonstrates SMA associated deletions. Hum. Molec. Genet. 6: 229-236, 1997. [PubMed: 9063743] [Full Text: https://doi.org/10.1093/hmg/6.2.229]
Humbert, S., van Vuuren, H., Lutz, Y., Hoeijmakers, J. H., Egly, J. M., Moncollin, V. p44 and p34 subunits of the BTF2/TFIIH transcription factor have homologies with SSL1, a yeast protein involved in DNA repair. EMBO J. 13: 2393-2398, 1994. [PubMed: 8194529] [Full Text: https://doi.org/10.1002/j.1460-2075.1994.tb06523.x]
Le May, N., Dubaele, S., De Santis, L. P., Billecocq, A., Bouloy, M., Egly, J.-M. TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus. Cell 116: 541-550, 2004. [PubMed: 14980221] [Full Text: https://doi.org/10.1016/s0092-8674(04)00132-1]
van der Steege, G., Draaijers, T. G., Grootscholten, P. M., Osinga, J., Anzevino, R., Velona, I., Den Dunnen, J. T., Scheffer, H., Brahe, C., van Ommen, G. J., Buys, H. C. M. A provisional transcript mzp of the spinal muscular atrophy (SMA) critical region. Europ. J. Hum. Genet. 3: 87-95, 1995. [PubMed: 7552146] [Full Text: https://doi.org/10.1159/000472281]