Alternative titles; symbols
HGNC Approved Gene Symbol: GTF2IRD2
Cytogenetic location: 7q11.23 Genomic coordinates (GRCh38) : 7:74,796,151-74,851,605 (from NCBI)
By searching for genes within the Williams-Beuren syndrome (WBS; 194050) critical region on chromosome 7, Tipney et al. (2004) identified a duplicated region containing at least 2 transcribed GTF2IRD2 genes, which they designated GTF2IRD2A and GTF2IRD2B (608900), and a pseudogene. They isolated mouse Gtf2ird2 and identified human GTF2IRD2A cDNAs. The human GTF2IRD2A protein contains 949 amino acids and has a calculated molecular mass of 107 kD. Its N-terminal half contains a leucine zipper motif, followed by 2 helix-loop-helix motifs (I repeats) that share homology with the TFII-I family of transcription factors (see 601679). The C-terminal half of GTF2IRD2A contains a CHARLIE8 transposable element-like sequence, including 3 transposase-related domains that may be functional, and a BED zinc finger DNA-binding motif. The 949-amino acid GTF2IRD2B protein has 6 C-terminal amino acid changes relative to GTF2IRD2A. Northern blot and RT-PCR analyses of mouse tissues showed nearly ubiquitous expression of Gtf2ird2. No expression was detected in day-9.5 or -10.5 mouse embryos. Tipney et al. (2004) identified GTF2IRD2 gene orthologs in several mammalian genomes, but not in fly, nematode, or pufferfish genomes.
By searching human and mouse EST databases for sequences similar to mouse Gtf2i (601679), Makeyev et al. (2004) identified human and mouse GTF2IRD2. They also identified a GTF2IRD2 splice variant in a lung epithelial cell cDNA library that utilizes an alternate first exon. GTF2IRD2 orthologs were present in trout, chicken, baboon, and rat genomes.
Makeyev et al. (2004) determined that the GTF2IRD2 gene contains 17 exons, including an alternate exon 1, and spans 57 kb. The promoter region contains putative TFIIB (GTF2B; 189963) recognition elements and binding sites for GC and CCAAT box-binding proteins, but no TATA boxes, initiators, or downstream promoter elements near the transcription start site. The mouse Gtf2ird2 gene has 16 exons and spans 34 kb.
By genomic sequence analysis, Tipney et al. (2004) mapped the GTF2IRD2A gene to a duplicated region of chromosome 7q11.23. It is located centromeric to the GTF2IRD2B gene and telomeric to a GTF2IRD2 pseudogene. By FISH, Tipney et al. (2004) mapped the single-copy mouse Gtf2ird2 gene to a region of chromosome 5G that shows homology of synteny to human chromosome 7q11.23.
Tipney et al. (2004) screened 4 WBS patients for deletions at chromosome 7q11.23 large enough to include the GTF2IRD2 genes. They identified 2 patients with deletions extending to the GTF2IRD2A gene, but the patients had no phenotypic differences compared with WBS patients having both copies of the GTF2IRD2A gene.
Makeyev, A. V., Erdenechimeg, L., Mungunsukh, O., Roth, J. J., Enkhmandakh, B., Ruddle, F. H., Bayarsaihan, D. GTF2IRD2 is located in the Williams-Beuren syndrome critical region 7q11.23 and encodes a protein with two TFII-I-like helix-loop-helix repeats. Proc. Nat. Acad. Sci. 101: 11052-11057, 2004. [PubMed: 15243160] [Full Text: https://doi.org/10.1073/pnas.0404150101]
Tipney, H. J., Hinsley, T. A., Brass, A., Metcalfe, K., Donnai, D., Tassabehji, M. Isolation and characterization of GTF2IRD2, a novel fusion gene and member of the TFII-I family of transcription factors, deleted in Williams-Beuren syndrome. Europ. J. Hum. Genet. 12: 551-560, 2004. [PubMed: 15100712] [Full Text: https://doi.org/10.1038/sj.ejhg.5201174]