TBX22 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | TBX22 , ABERS, CLPA, CPX, TBXX, dJ795G23.1, T-box 22, T-box transcription factor 22 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 300307 MGI: 2389465 HomoloGene: 9666 GeneCards: TBX22 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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T-box transcription factor TBX22 is a protein that in humans is encoded by the TBX22 gene. [5]
TBX22 is a member of a phylogenetically conserved family of proteins that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Mutations in this gene have been associated with the inherited X-linked disorder, cleft palate with ankyloglossia (tongue-tie), and it is believed to play a major role in human palatogenesis. [5] It has previously been mapped to the long arm of the X chromosome and it has now been demonstrated that mutations in the gene TBX22 are the cause of this syndrome. [6] TBX22 mutations also result in non-syndromic cleft palate in some populations. [7]
TBX22 is composed of seven exons spanning 8.7 kilobases of genomic DNA in Xq21.1. The TBX22 mRNA is 2099 base pairs long and encodes a 400-amino-acids protein containing a T-domain in its NH2-terminal region which has the unique feature of missing 20 amino-acids relative to the other known T-domains. [8]
T-box genes are members of a family of transcriptional regulators that contain a region encoding a conserved DNA-binding motif of approximately 200 amino acids: the T-domain. These genes are grouped together on the basis of the homology existing between their products and the mouse Brachyury (or T) protein. In human and mouse, numerous T-domain-containing genes have been identified so far and mapped throughout the genome. The spatio-temporal expression of these genes is strictly regulated during the development of both vertebrates and invertebrates. [8]
Functional studies have demonstrated that several T-box genes are involved in mesoderm specification in the developing embryo of mouse or Xenopus . In mice, the Brachyury gene is expressed in early mesoderm cells and its expression then becomes restricted to the notochord. The Brachyury protein binds as a dimer to a 20-nucleotide partially palindromic sequence recognized by its T-domain. More generally, T-box genes have been shown to be critical during development for proper morphogenesis and organogenesis. Abnormal expression of several T-box genes has been shown to cause developmental anomalies in mouse, Drosophila or zebrafish.
In humans, two T-box genes are involved in inherited disorders: mutations in TBX5 cause Holt–Oram syndrome, whereas mutations in TBX3 cause ulnar–mammary syndrome. [8]
Mutations in TBX22 cause X-linked cleft palate and ankyloglossia. [9] CPX has been described in a small number of families exhibiting a strong X linked Mendelian inheritance. The cleft phenotype predominantly affects males who show variation ranging from a complete cleft of the secondary palate, submucous cleft, or bifid uvula to high arched palate. Ankyloglossia is frequently seen in affected patients and carrier females, and has proved to be a useful indicator of CPX. Temporal and spatial studies using in situ hybridization in both human and mouse has shown that TBX22/Tbx22 is expressed primarily in the palatal shelves and tongue during palatogenesis, indicating a specific role of TBX22 in both palatal and tongue development. In addition to families with well defined X linked inheritance, TBX22 mutations have been identified in several families where pedigree size and/or family history were too limited to predict mode of inheritance. In these cases, ascertainment was largely based on the presence of ankyloglossia as well as cleft palate. [10]
It has been demonstrated that TBX22 makes a significant contribution to the prevalence of cleft palate at least in the Brazilian and the North American cohorts. [8] To date, 10 different TBX22 mutations have been reported in patients with CP and/or ankyloglossia. [11] These include small deletions/insertions, nonsense, splice site, frameshift and missense alterations. [7]
Treacle protein is a protein that in humans is encoded by the TCOF1 gene.
T-box transcription factor TBX1 also known as T-box protein 1 and testis-specific T-box protein is a protein that in humans is encoded by the TBX1 gene. Genes in the T-box family are transcription factors that play important roles in the formation of tissues and organs during embryonic development. To carry out these roles, proteins made by this gene family bind to specific areas of DNA called T-box binding element (TBE) to control the expression of target genes.
T-box transcription factor T, also known as Brachyury protein, is encoded for in humans by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra.
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent infections, developmental delay, learning problems and cleft palate. Associated conditions include kidney problems, schizophrenia, hearing loss and autoimmune disorders such as rheumatoid arthritis or Graves' disease.
Interferon regulatory factor 6 also known as IRF6 is a protein that in humans is encoded by the IRF6 gene.
Abruzzo–Erickson syndrome is an extremely rare disorder characterized by deafness, protruding ears, coloboma, a cleft palate or palatal rugosity, radial synostosis, and short stature. It was first characterized by Abruzzo and Erickson in 1977 as a CHARGE like syndrome as variably expressed among a family of two brothers, their mother, and their maternal uncle. Members of this family exhibited many of the CHARGE symptoms, but notably did not have choanal atresia and the brothers experienced typical genital development. Due to the recent discovery of this disorder, its etiology is not fully known but it is understood that it arises from mutations on the TBX22 gene on the X-chromosome. The disorder is inherited in an X-linked recessive manner. There is currently no known cure but its symptoms can be treated.
T-box refers to a group of transcription factors involved in embryonic limb and heart development. Every T-box protein has a relatively large DNA-binding domain, generally comprising about a third of the entire protein that is both necessary and sufficient for sequence-specific DNA binding. All members of the T-box gene family bind to the "T-box", a DNA consensus sequence of TCACACCT.
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.
T-box transcription factor TBX19 is a protein that in humans is encoded by the TBX19 gene.
Homeobox protein MSX-1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and is responsive to thyroid hormone. MSX1 is also expressed in highly differentiated pituitary cells which until recently was thought to be expressed exclusively during embryogenesis. There is a highly conserved structural organization of the members of the MSX family of genes and their abundant expression at sites of inductive cell–cell interactions in the embryo suggest that they have a pivotal role during early development.
Protein patched homolog 1 is a protein that is the member of the patched family and in humans is encoded by the PTCH1 gene.
T-box transcription factor TBX5, is a protein that in humans is encoded by the TBX5 gene.
T-box transcription factor TBX3 is a protein that in humans is encoded by the TBX3 gene.
Collagen alpha-1(XI) chain is a protein that in humans is encoded by the COL11A1 gene.
Forkhead box protein E1 is a protein that in humans is encoded by the FOXE1 gene.
Transcription factor AP-2 alpha, also known as TFAP2A, is a protein that in humans is encoded by the TFAP2A gene.
Ventral anterior homeobox 1 is a protein that in humans is encoded by the VAX1 gene.
Homeobox protein Hox-A2 is a protein that in humans is encoded by the HOXA2 gene.
Special AT-rich sequence-binding protein 2 (SATB2) also known as DNA-binding protein SATB2 is a protein that in humans is encoded by the SATB2 gene. SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling. SATB2 shows a restricted mode of expression and is expressed in certain cell nuclei. The SATB2 protein is mainly expressed in the epithelial cells of the colon and rectum, followed by the nuclei of neurons in the brain.
T-box transcription factor TBX15 is protein that is encoded in humans by the Tbx15 gene, mapped to Chromosome 3 in mice and Chromosome 1 in humans. Tbx15 is a transcription factor that plays a key role in embryonic development. Like other members of the T-box subfamily, Tbx15 is expressed in the notochord and primitive streak, where it assists with the formation and differentiation of the mesoderm. It is steadily downregulated after segmentation of the paraxial mesoderm.