Alternative titles; symbols
HGNC Approved Gene Symbol: GTF2E2
Cytogenetic location: 8p12 Genomic coordinates (GRCh38): 8:30,578,318-30,658,236 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8p12 | Trichothiodystrophy 6, nonphotosensitive | 616943 | Autosomal recessive | 3 |
The GTF2E2 gene encodes the beta (34-kD) subunit of the general transcription factor TFIIE. The structure of TFIIE appears to be a heterotetramer of 2 alpha (189962) and 2 beta subunits, both subunits being required for optimal reconstituted basal-level transcription (summary by Peterson et al., 1991).
Human TFIIE consists of 2 subunits of relative molecular masses 56,000 and 34,000. Peterson et al. (1991) isolated human cDNA clones for both subunits of the general transcription factor IIE. Using purified recombinant proteins they found that both subunits are essential to form a stable preinitiation complex and to reconstitute basal-level and Sp1-activated (189906) transcription in vitro.
Imbert et al. (1996) studied the chromosomal region 8p21-p12 by constructing an integrated physical and genetic map extending from the genes NEFL (162280) located at 8p21, to FGFR1 (136350) located at 8p11.2-p11.1. The map comprised a series of contigs of YACs. Imbert et al. (1996) precisely mapped the GTFE2 gene within the YAC contigs.
In 2 unrelated patients with a nonphotosensitive form of trichothiodystrophy (TTD6; 616943), Kuschal et al. (2016) identified homozygosity for different mutations in the GTF2E2 gene, A150P (189964.0001) and D187Y (189964.0002).
In a 10-year-old Asian boy with nonphotosensitive trichothiodystrophy (TTD6; 616943), Kuschal et al. (2016) identified homozygosity for a c.448G-C transversion (c.448G-C, NM_002095.4) in the GTF2E2 gene, resulting in an ala150-to-pro (A150P) substitution at a highly conserved residue within a leucine repeat motif of the wing helix-2 (WH2) domain. His first-cousin parents were heterozygous for the mutation, which was not found in the dbSNP database. Immunoblot analysis of patient fibroblasts revealed marked reductions in the levels of both the alpha (189962) and beta (encoded by GTF2E2) subunits of the TFIIE complex compared to healthy relative and controls. In addition, reduced phosphorylation of TFIIE-alpha was observed in patient cells.
In a 16-year-old Moroccan girl with nonphotosensitive trichothiodystrophy (TTD6; 616943), Kuschal et al. (2016) identified homozygosity for a c.559G-T transversion (c.559G-T, NM_002095.4) in the GTF2E2 gene, resulting in an asp187-to-tyr (D187Y) substitution at a highly conserved residue within a delta-3 region of the wing helix-2 (WH2) domain. Her distantly related parents and her unaffected sister were each heterozygous for the mutation, which was not found in the dbSNP database. Immunoblot analysis of patient fibroblasts and lymphoblasts revealed marked reductions in the levels of both the alpha (189962) and beta subunits of the TFIIE complex compared to healthy relatives and controls. In addition, reduced phosphorylation of TFIIE-alpha was observed in patient cells.
Imbert, A., Chaffanet, M., Essioux, L., Noguchi, T., Adelaide, J., Kerangueven, F., Le Paslier, D., Bonaiti-Pellie, C., Sobol, H., Birnbaum, D., Pebusque, M.-J. Integrated map of the chromosome 8p12-p21 region, a region involved in human cancers and Werner syndrome. Genomics 32: 29-38, 1996. [PubMed: 8786118] [Full Text: https://doi.org/10.1006/geno.1996.0073]
Kuschal, C., Botta, E., Orioli, D., Digiovanna, J. J., Seneca, S., Keymolen, K., Tamura, D., Heller, E., Khan, S. G., Caligiuri, G., Lanzafame, M., Nardo, T., and 9 others. GTF2E2 mutations destabilize the general transcription factor complex TFIIE in individuals with DNA repair-proficient tricothiodystrophy. Am. J. Hum. Genet. 98: 627-642, 2016. [PubMed: 26996949] [Full Text: https://doi.org/10.1016/j.ajhg.2016.02.008]
Peterson, M. G., Inostroza, J., Maxon, M. E., Flores, O., Admon, A., Reinberg, D., Tjian, R. Structure and functional properties of human general transcription factor IIE. Nature 354: 369-373, 1991. [PubMed: 1956398] [Full Text: https://doi.org/10.1038/354369a0]