Alternative titles; symbols
HGNC Approved Gene Symbol: THADA
Cytogenetic location: 2p21 Genomic coordinates (GRCh38): 2:43,230,851-43,596,038 (from NCBI)
By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (2000) cloned THADA, which they designated KIAA1767. The cDNA contains repetitive elements in its 5-prime end, and the deduced protein contains 894 amino acids. RT-PCR ELISA detected high expression in liver and moderate expression in all other adult and fetal tissues examined.
Using positional cloning and 3-prime RACE to identify the gene disrupted in thyroid adenomas with chromosome 2p21 aberrations, Rippe et al. (2003) cloned THADA. The full-length protein contains 1,954 amino acids and has a calculated molecular mass of 220 kD. Rippe et al. (2003) also identified a THADA splice variant lacking exons 27 and 28. Northern blot analysis detected variable expression of a 6.2-kb THADA transcript in all tissues examined.
Drieschner et al. (2007) determined that the full-length THADA protein contains an ARM repeat for protein-protein interactions. Human THADA shares 95.9%, 78.2%, and 64.9% amino acid similarity with African green monkey, mouse, and chicken Thada, respectively. The most conserved region of THADA among vertebrates corresponds to amino acids 1033 to 1415 of human THADA.
Rippe et al. (2003) determined that the THADA gene contains 38 exons and spans about 365 kb. Drieschner et al. (2007) stated that the start codon of THADA is in exon 2.
By genomic sequence analysis, Rippe et al. (2003) mapped the THADA gene to chromosome 2p21.
Rearrangements at chromosome 2p21 are found in about 10% of benign thyroid tumors. Rippe et al. (2003) found that the 2p21 breakpoint in 2 thyroid adenomas characterized by translocations t(2;20;3) (p21;q11.2;p25) and t(2;7)(p21;p15), respectively, occurred in exon 28 of the THADA gene. The sequences derived from chromosomes 3p25 and 7p15 did not appear to include a coding region. Drieschner et al. (2007) determined that the THADA truncations observed in thyroid adenomas by Rippe et al. (2003) disrupted the most conserved region of the THADA protein among vertebrates.
Green et al. (2010) published a draft sequence of the Neandertal genome. Comparisons of the Neandertal genome to the genomes of 5 present-day humans from different parts of the world identified a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. Green et al. (2010) identified a total of 212 regions containing putative selective sweeps. Of the 20 widest regions, 5 contained no protein-coding genes and the others had 1 to 12 genes. The widest region is located on chromosome 2 and contains the gene THADA, where a region of 336 kb is depleted of derived alleles in Neandertals. SNPs in the vicinity of THADA have been associated with type 2 diabetes (125853), and THADA expression differs between individuals with diabetes and healthy controls (Parikh et al., 2009). Green et al. (2010) also showed that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.
Drieschner, N., Kerschling, S., Soller, J. T., Rippe, V., Belge, G., Bullerdiek, J., Nimzyk, R. A domain of the thyroid adenoma associated gene (THADA) conserved in vertebrates becomes destroyed by chromosomal rearrangements observed in thyroid adenomas. Gene 403: 110-117, 2007. [PubMed: 17889454] [Full Text: https://doi.org/10.1016/j.gene.2007.06.029]
Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., Hansen, N. F., Durand, E. Y., and 44 others. A draft sequence of the Neandertal genome. Science 328: 710-722, 2010. [PubMed: 20448178] [Full Text: https://doi.org/10.1126/science.1188021]
Nagase, T., Kikuno, R., Hattori, A., Kondo, Y., Okumura, K., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 347-355, 2000. [PubMed: 11214970] [Full Text: https://doi.org/10.1093/dnares/7.6.347]
Parikh, H., Lyssenko, V., Groop, L. C. Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus. BMC Med. Genomics 2: 72, 2009. Note: Electronic Article. [PubMed: 20043853] [Full Text: https://doi.org/10.1186/1755-8794-2-72]
Rippe, V., Drieschner, N., Meiboom, M., Escobar, H. M., Bonk, U., Belge, G., Bullerdiek, J. Identification of a gene rearranged by 2p21 aberrations in thyroid adenomas. Oncogene 22: 6111-6114, 2003. [PubMed: 12955091] [Full Text: https://doi.org/10.1038/sj.onc.1206867]