TBX22 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- TBX22 (HGNC:11600) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- T-box transcription factor 22
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- CPX, CLPA
- Alias symbols
- No aliases found
- %HI
- 43.82(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.98(Read more about gnomAD pLI score)
- LOEUF
- 0.3(Read more about gnomAD LOEUF score)
- Cytoband
- Xq21.1
- Genomic Coordinates
-
GRCh37/hg19: chrX:79270252-79287273 NCBI Ensembl UCSC GRCh38/hg38: chrX:80014753-80031774 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001109878.2 ENST00000373296.8 (Read more about MANE Select)
- Function
- Probable transcriptional regulator involved in developmental processes. This is major determinant crucial to palatogenesis. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- 0010560 Monarch
-
PUBMED:
11559848
Braybrook et al. (2001) report several families with cleft palate and ankyloglossia (CPX) with variants in TBX22, including one nonsense (E56X;166G>T), one frameshift (664delC), two splice-site (IVS4+1G>A; IVS6+1G>C), and two missense variants. All six variants segregated with the disorder in the respective families, and none was present in 200 control chromosomes. The authors note that they "attempted to amplify cDNA from across the splice-site mutation in a cell line from an Icelandic male with cleft palate and ankyloglossia, [and were unable to] detect any PCR product, even with primer pairs from other portions of the transcript." They hypothesize that the particular splice site variant may result in nonsense-mediated decay.
-
PUBMED:
14729838
Marcano ACB et al., (2004) described 5 variants in coding exons and 4 putative splicing variants in TBX22 gene in a cohort of 256 random CP patients with 18 being syndromic patients. Among them one frameshift mutation, 1056-106delGC was reported. In addition, a splicing mutation, IVS4+1G>A, in all 6 affected males in a four generation large family W; another missense, 790A>T (N264Y) in exon 5, all 4 affected males in a three generation family K.
-
PUBMED:
17868388
Suphapeetiporn K et al. (2007) reported 4 unrelated Thai patients with apparently non-syndromic cleft palate and variants in TBX22, including one frameshift variant, 1252delG, predicted to result in premature termination. This variant was found in a female with non-syndromic cleft palate and her father with bifid uvula. A paternal uncle was reported to have isolated cleft soft palate, but no testing was done on this individual. The variant was not found in 112 ethnically-matched unaffected control chromosomes. The other four potentially pathogenic missense mutations are 359G->A (R120Q), 452G->T (R151L), 1166C->A (P389Q).
-
PUBMED:
22784330
Pauws E et al., (2013) reported three splice mutation (c.593-5T>A, c.767+5G>A and c.767+1G>A) in three affected individuals. The first one affecting acceptor side was tracked with the phenotype in a family; the latter two splice donor variants were identified in patients with classic CPX phenotypes. All three variants were predicted to abolish normal mRNA splicing and an in vitro assay indicated that use of alternative splice sites was a likely outcome.
-
PUBMED:
25373698
Fu X et al., (2015) reported a loss-of-function mutation, -73G>A, in the promoter of TBX22 gene in a six-generation family of the CPO (cleft palate only) with obvious phenotypes of both cleft palate and hyper-nasal speech. The mutation was detected in all five affected male members cosegregating with the affected phenotype and heterozygote occurred only in some unaffected females of the family, suggesting an X-linked transmission of the mutation in the family. Functional study using EMSA and ChiP assays, as well as cell con-transfection showed this mutation disrupts the binding site of ETS-1, thus markedly decreases the activity of the TBX22 promoter, which is likely to lead to the birth defect of the CPO without ankyloglossia.
-
PUBMED:
29932061
Dai J et al., (2018) reported a novel essential splicing site mutation, IVS6-1G>C, in a family with cleft palate. The bioinformatic analysis results showed that this mutation would lead to abnormal transcription or translation, followed by a loss of function of TBX22.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.