Alternative titles; symbols
HGNC Approved Gene Symbol: TSR2
Cytogenetic location: Xp11.22 Genomic coordinates (GRCh38) : X:54,440,404-54,448,032 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xp11.22 | ?Diamond-Blackfan anemia 14 with mandibulofacial dysostosis | 300946 | X-linked recessive | 3 |
TSR2 is a negative regulator of NF-kappa-B (NFKB; see 164011) (He et al., 2011).
By EST database analysis and PCR of a mixed human cDNA library, He et al. (2011) cloned TSR2. The deduced 191-amino acid protein has a predicted molecular mass of 20.9 kD. It contains a conserved WGG motif found in proteins involved in pre-rRNA processing. Northern blot analysis detected variable expression of a 1.5-kb TSR2 in the 5 human tissues examined: brain, thyroid, larynx, lung, and heart. TSR2 was also expressed in all human cell lines examined. Fluorescence-tagged TSR2 was expressed in both the nucleus and cytosol of transfected HEp-2 human epidermal cells. Database analysis revealed conservation of TSR2 in vertebrates.
He et al. (2011) found that overexpression of TSR2 in HEp-2 cells inhibited expression of an NFKB reporter gene in the presence or absence of TNF-alpha (TNFA; 191160), an inducer of NFKB. EMSA of nuclear extracts revealed that TSR2 diminished binding of NFKB to its specific DNA probe. Overexpression of TSR2 also induced apoptosis in HEp-2 cells.
He et al. (2011) determined that the TSR2 gene has 5 exons.
He et al. (2011) stated that the TSR2 gene maps to chromosome Xp11.22.
In 2 male first cousins with Diamond-Blackfan anemia-14 with mandibulofacial dysostosis (DBA14; 300946), originally reported by Gripp et al. (2001), Gripp et al. (2014) identified a hemizygous missense mutation in the TSR2 gene (E64G; 300945.0001).
In 2 male first cousins with Diamond-Blackfan anemia-14 with mandibulofacial dysostosis (DBA14; 300946), originally reported by Gripp et al. (2001), Gripp et al. (2014) identified a hemizygous c.191A-G transition in the TSR2 gene, resulting in a glu64-to-gly (E64G) substitution at a highly conserved residue. The mutation, which was found by sequencing of candidate ribosomal protein genes, segregated with the disorder in the family and was not present in the dbSNP (build 137), 1000 Genomes Project, or Exome Sequencing Project databases. Functional studies of the variant were not performed, but Gripp et al. (2014) noted that TSR2 is involved in processing and maturation of rRNA and binds to RPS26 (603701), which is mutated in Diamond-Blackfan anemia-10 (DBA10; 613309).
Gripp, K. W., Curry, C., Olney, A. H., Sandoval, C., Fisher, J., Chong, J. X.-L., UW Center for Mendelian Genomics, Pilchman, L., Sahraoui, R., Stabley, D. L., Sol-Church, K. Diamond-Blackfan anemia with mandibulofacial dystostosis (sic) is heterogeneous, including the novel DBA genes TSR2 and RPS28. Am. J. Med. Genet. 164A: 2240-2249, 2014. [PubMed: 24942156] [Full Text: https://doi.org/10.1002/ajmg.a.36633]
Gripp, K. W., McDonald-McGinn, D. M., La Rossa, D., McGain, D., Federman, N., Vlachos, A., Glader, B. E., McKenzie, S. E., Lipton, J. M., Zackai, E. H. Bilateral microtia and cleft palate in cousins with Diamond-Blackfan anemia. Am. J. Med. Genet. 101: 268-274, 2001. [PubMed: 11424144] [Full Text: https://doi.org/10.1002/ajmg.1329]
He, H., Zhu, D., Sun, J., Pei, R., Jia, S. The novel protein TSR2 inhibits the transcriptional activity of nuclear factor-kappa-B and induces apoptosis. Molec. Biol. (Mosk) 45: 451-457, 2011. [PubMed: 21790011]