Gene Symbol: TBX22
Description: T-box 22
Alias: ABERS, CLPA, CPX, TBXX, dJ795G23.1, T-box transcription factor TBX22, T-box protein 22
Species: human
Products:     TBX22

Top Publications

  1. Braybrook C, Lisgo S, Doudney K, Henderson D, Marcano A, Strachan T, et al. Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients. Hum Mol Genet. 2002;11:2793-804 pubmed
    ..defect in CPX was identified, where unique mutations were found in the T-box-containing transcription factor TBX22. Here we report two new familial cases with novel missense and insertion mutations, each occurring within the T-..
  2. Kantaputra P, Paramee M, Kaewkhampa A, Hoshino A, Lees M, McEntagart M, et al. Cleft lip with cleft palate, ankyloglossia, and hypodontia are associated with TBX22 mutations. J Dent Res. 2011;90:450-5 pubmed publisher
    X-linked cleft palate and ankyloglossia (CPX) are caused by mutations in the TBX22 transcription factor...
  3. Braybrook C, Doudney K, Marçano A, Arnason A, Bjornsson A, Patton M, et al. The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia. Nat Genet. 2001;29:179-83 pubmed
    ..we show that CPX is caused by mutations in the gene encoding the recently described T-box transcription factor TBX22 (ref. 14)...
  4. Marçano A, Doudney K, Braybrook C, Squires R, Patton M, Lees M, et al. TBX22 mutations are a frequent cause of cleft palate. J Med Genet. 2004;41:68-74 pubmed
  5. Suphapeetiporn K, Tongkobpetch S, Siriwan P, Shotelersuk V. TBX22 mutations are a frequent cause of non-syndromic cleft palate in the Thai population. Clin Genet. 2007;72:478-83 pubmed
    Mutations in the TBX22 gene underlie an X-linked malformation syndrome with cleft palate (CP) and ankyloglossia. Its mutations also result in non-syndromic CP in some populations...
  6. Jagomagi T, Nikopensius T, Krjutskov K, Tammekivi V, Viltrop T, Saag M, et al. MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. Eur J Oral Sci. 2010;118:213-20 pubmed publisher
    ..This study provides further evidence implicating MSX1 and MTHFR in the etiology of nonsyndromic CL/P across different populations...
  7. Ichikawa E, Watanabe A, Nakano Y, Akita S, Hirano A, Kinoshita A, et al. PAX9 and TGFB3 are linked to susceptibility to nonsyndromic cleft lip with or without cleft palate in the Japanese: population-based and family-based candidate gene analyses. J Hum Genet. 2006;51:38-46 pubmed
    ..population, relationships between CL/P or CPO and seven candidate genes (TGFB3, DLX3, PAX9, CLPTM1, TBX10, PVRL1, TBX22) that showed positive associations in other populations and are expressed in the oral/lip region in developing ..
  8. Andreou A, Pauws E, Jones M, Singh M, Bussen M, Doudney K, et al. TBX22 missense mutations found in patients with X-linked cleft palate affect DNA binding, sumoylation, and transcriptional repression. Am J Hum Genet. 2007;81:700-12 pubmed
    The T-box transcription factor TBX22 is essential for normal craniofacial development, as demonstrated by the finding of nonsense, frameshift, splice-site, or missense mutations in patients with X-linked cleft palate (CPX) and ..
  9. Carinci F, Scapoli L, Palmieri A, Zollino I, Pezzetti F. Human genetic factors in nonsyndromic cleft lip and palate: an update. Int J Pediatr Otorhinolaryngol. 2007;71:1509-19 pubmed
    ..In addition, MTHFR, TGF-beta3, and RARalpha play a role in cleft onset. In CPI one gene has been identified (TBX22) at present, but others are probably involved...

More Information


  1. Chaabouni M, Smaoui N, Benneji N, M rad R, Jemaa L, Hachicha S, et al. Mutation analysis of TBX22 reveals new mutation in Tunisian CPX family. Clin Dysmorphol. 2005;14:23-5 pubmed
    ..Linkage studies resulted in mapping CPX to Xq13-q 21-31 region. TBX22 was identified as causing CPX...
  2. Hoeksema M, Jonker M, Bel K, Brul S, ter Kuile B. Genome rearrangements in Escherichia coli during de novo acquisition of resistance to a single antibiotic or two antibiotics successively. BMC Genomics. 2018;19:973 pubmed publisher
    ..Partial deletion of clpS and clpA occurred in strains exposed to enrofloxacin and tetracycline...
  3. Marsee J, Ridings A, Yu T, Miller J. Mycobacterium tuberculosis ClpC1 N-Terminal Domain Is Dispensable for Adaptor Protein-Dependent Allosteric Regulation. Int J Mol Sci. 2018;19: pubmed publisher
    ..that include MecA regulation of Bacillus subtilis ClpC or ClpS-mediated control of Escherichia coli ClpA. No adaptor protein-mediated control has been reported for mycobacterial ClpC1...
  4. Dai J, Xu C, Wang G, Liang Y, Wan T, Zhang Y, et al. Novel TBX22 mutations in Chinese nonsyndromic cleft lip/palate families. J Genet. 2018;97:411-417 pubmed
    i>TBX22 is a gene which contribute to cleft lip/palate, and many mutation sites of TBX22 have been reported...
  5. Zeng L, Zhuang X, Huang L, Zhang Y, Chen C, Dong K, et al. Comparative subproteome analysis of three representative Leptospira interrogans vaccine strains reveals cross-reactive antigens and novel virulence determinants. J Proteomics. 2015;112:27-37 pubmed publisher
    ..Interestingly, LipL45, ClpA and ClpB, exhibiting obvious amino acid mutations among str.56601, str...
  6. Kim J, Kimber M, Nishimura K, Friso G, Schultz L, Ponnala L, et al. Structures, Functions, and Interactions of ClpT1 and ClpT2 in the Clp Protease System of Arabidopsis Chloroplasts. Plant Cell. 2015;27:1477-96 pubmed publisher
    ..4- and 2.0-Ã… resolution) and detailed the similarities to the N-domains of bacterial ClpA/C chaperones...
  7. Rivera Rivera I, Román Hernández G, Sauer R, Baker T. Remodeling of a delivery complex allows ClpS-mediated degradation of N-degron substrates. Proc Natl Acad Sci U S A. 2014;111:E3853-9 pubmed publisher
    ..ClpS binds the substrate N-degron and assembles into a high-affinity ClpS-substrate-ClpA complex, but how the N-degron is transferred from ClpS to the axial pore of the AAA+ ClpA unfoldase to initiate ..
  8. Olivares A, Nager A, Iosefson O, Sauer R, Baker T. Mechanochemical basis of protein degradation by a double-ring AAA+ machine. Nat Struct Mol Biol. 2014;21:871-5 pubmed publisher
    ..Using single-molecule optical trapping, we determine how the double-ring ClpA enzyme from Escherichia coli, in complex with the ClpP peptidase, mechanically degrades proteins...
  9. Sabitova Y, Fomenko N, Tikunov A, Stronin O, Khasnatinov M, Abmed D, et al. Multilocus sequence analysis of Borrelia burgdorferi sensu lato isolates from Western Siberia, Russia and Northern Mongolia. Infect Genet Evol. 2018;62:160-169 pubmed publisher
    ..Genotyping of Borrelia strains using the clpA, pepX, and p83/100 genes demonstrated the same result as genotyping based on MLST; and further investigations are ..
  10. Baytshtok V, Baker T, Sauer R. Assaying the kinetics of protein denaturation catalyzed by AAA+ unfolding machines and proteases. Proc Natl Acad Sci U S A. 2015;112:5377-82 pubmed publisher
    ..For example, AAA+ ClpX and ClpA hexamers collaborate with the self-compartmentalized ClpP peptidase to unfold and degrade specific proteins in ..
  11. Huang H, Lin Y, Chen P, Li L, Ning H, Yang T. ClpA and HtpX Proteases Are Involved in Intrinsic Aminoglycoside Resistance of Stenotrophomonas maltophilia and Are Potential Aminoglycoside Adjuvant Targets. Antimicrob Agents Chemother. 2018;62: pubmed publisher
    ..system, SmeYZ pump, and aminoglycoside resistance was assessed in Stenotrophomonas maltophilia The clpA, clpS, clpP, and htpX genes were upregulated in response to kanamycin exposure...
  12. Ji Z, Yan H, Cui Q, Wang E, Chen W, Chen W. Genetic divergence and gene flow among Mesorhizobium strains nodulating the shrub legume Caragana. Syst Appl Microbiol. 2015;38:176-83 pubmed publisher
    ..Five core genes-atpD, glnII, gyrB, recA, and rpoB, six heat-shock factor genes-clpA, clpB, dnaK, dnaJ, grpE, and hlsU, and five nodulation genes-nodA, nodC, nodD, nodG, and nodP, of 72 representative ..
  13. Duran E, Lucius A. ATP hydrolysis inactivating Walker B mutation perturbs E. coli ClpA self-assembly energetics in the absence of nucleotide. Biophys Chem. 2018;242:6-14 pubmed publisher
    E. coli ClpA is an AAA+ (ATPase Associated with diverse cellular Activities) chaperone that catalyzes the ATP-dependent unfolding and translocation of substrate proteins for the purposes of proper proteome maintenance...
  14. Song C, Sundqvist G, Malm E, de Bruijn I, Kumar A, van de Mortel J, et al. Lipopeptide biosynthesis in Pseudomonas fluorescens is regulated by the protease complex ClpAP. BMC Microbiol. 2015;15:29 pubmed publisher
    ..This study provides evidence that the chaperone ClpA, together with the serine protease ClpP, regulates the biosynthesis of the LP massetolide in Pseudomonas ..
  15. Chu B, Colognori D, Yang G, Xie M, Lindsey Bergman R, Piacentini J. Mediators of exposure therapy for youth obsessive-compulsive disorder: specificity and temporal sequence of client and treatment factors. Behav Ther. 2015;46:395-408 pubmed publisher
    ..Regression analysis using Generalized Estimation Equations and cross-lagged panel analysis (CLPA) were conducted to model anxiety change within and across sessions, to determine formal mediators of anxiety change,..
  16. Giordano M, Gertosio C, Pagani S, Meazza C, Fusco I, Bozzola E, et al. A 5.8 Mb interstitial deletion on chromosome Xq21.1 in a boy with intellectual disability, cleft palate, hearing impairment and combined growth hormone deficiency. BMC Med Genet. 2015;16:74 pubmed publisher
    ..8 Mb rearrangement encompasses 14 genes, including BRWD3 (involved in X-linked intellectual disability), TBX22 (a gene whose alterations have been related to the presence of cleft palate), POU3F4 (mutated in X-linked deafness)..
  17. Li T, Weaver C, Lin J, Duran E, Miller J, Lucius A. Escherichia coli ClpB is a non-processive polypeptide translocase. Biochem J. 2015;470:39-52 pubmed publisher
    ..Using single-turnover FRET experiments we show that ClpB containing the IGL loop from ClpA does not translocate substrate through its axial channel and into ClpP for proteolytic degradation...
  18. Stein B, Grant R, Sauer R, Baker T. Structural Basis of an N-Degron Adaptor with More Stringent Specificity. Structure. 2016;24:232-42 pubmed publisher
    ..Here, we demonstrate that both ClpS1 and ClpS2 from A. tumefaciens deliver N-end-rule substrates to ClpA, but ClpS2 has more stringent binding specificity, recognizing only a subset of the canonical bacterial N-end-rule ..
  19. Hall B, Breidenstein E, de la Fuente Nunez C, Reffuveille F, Mawla G, Hancock R, et al. Two Isoforms of Clp Peptidase in Pseudomonas aeruginosa Control Distinct Aspects of Cellular Physiology. J Bacteriol. 2017;199: pubmed publisher
    ..the biological roles of ClpP1 and ClpP2 and biochemical assays to characterize purified ClpP1, ClpP2, ClpX, and ClpA. Interestingly, ClpP1 and ClpP2 have distinct intracellular roles for motility, pigment production, iron scavenging,..
  20. Lin J, Lucius A. Analysis of Linked Equilibria. Methods Enzymol. 2015;562:161-86 pubmed publisher
    ..We have been studying two example members, Escherichia coli ClpA and ClpB. These two enzymes are active as hexameric rings that both require nucleotide binding for assembly...
  21. Amato S, Brynildsen M. Persister Heterogeneity Arising from a Single Metabolic Stress. Curr Biol. 2015;25:2090-8 pubmed publisher
    ..We discovered that diauxie-dependent formation of ampicillin persisters required RelA and that loss of clpA, ssrA, or smpB eliminated persister formation through relaxation of the stringent response...
  22. Nimmagadda S, Buchtová M, Fu K, Geetha Loganathan P, Hosseini Farahabadi S, Trachtenberg A, et al. Identification and functional analysis of novel facial patterning genes in the duplicated beak chicken embryo. Dev Biol. 2015;407:275-88 pubmed publisher
    ..Expression of TP63, TBX22, BMP4 and FOXE1, all human clefting genes, were upregulated...
  23. Jungnick S, Margos G, Rieger M, Dzaferovic E, Bent S, Overzier E, et al. Borrelia burgdorferi sensu stricto and Borrelia afzelii: Population structure and differential pathogenicity. Int J Med Microbiol. 2015;305:673-81 pubmed publisher
    ..The scheme employed used eight chromosomally located housekeeping genes (i.e. clpA, clpX, nifS, pepX, pyrG, recG, rplB and uvrA)...
  24. Meenakshi S, Munavar M. Suppression of capsule expression in Δlon strains of Escherichia coli by two novel rpoB mutations in concert with HNS: possible role for DNA bending at rcsA promoter. Microbiologyopen. 2015;4:712-29 pubmed publisher
    ..coli in concert with HNS. clpA, clpB, clpY, and clpQ mutations do not affect this capsule expression suppressor (Ces) phenotype...
  25. Margos G, Hojgaard A, Lane R, Cornet M, Fingerle V, Rudenko N, et al. Multilocus sequence analysis of Borrelia bissettii strains from North America reveals a new Borrelia species, Borrelia kurtenbachii. Ticks Tick Borne Dis. 2010;1:151-8 pubmed publisher
    ..We amplified internal fragments of 8 housekeeping genes (clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA) located on the main linear chromosome by polymerase chain reaction...
  26. Sangpuii L, Dixit S, Kumawat M, Apoorva S, Kumar M, Kappala D, et al. Comparative roles of clpA and clpB in the survival of S. Typhimurium under stress and virulence in poultry. Sci Rep. 2018;8:4481 pubmed publisher
    ..In the current study, comparative roles of two such Clps, ClpA (involved in proteolysis) and ClpB (involved in protein disaggregation and refolding) in the survival of Salmonella ..
  27. Phan M, Conte F, Khandelwal K, Ockeloen C, Bartzela T, Kleefstra T, et al. Tooth agenesis and orofacial clefting: genetic brothers in arms?. Hum Genet. 2016;135:1299-1327 pubmed
    ..underlying the co-occurrence of the two congenital defects: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFα, TGFβ3, TGFβR1, TGFβR2, FGF8, FGFR1, KISS1R, WNT3, WNT5A, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, ..
  28. AhYoung A, Koehl A, Vizcarra C, Cascio D, Egea P. Structure of a putative ClpS N-end rule adaptor protein from the malaria pathogen Plasmodium falciparum. Protein Sci. 2016;25:689-701 pubmed publisher
    ..bacteria, the ClpS adaptor binds and delivers N-end rule substrates for their degradation upon association with the ClpA/P chaperone/protease. Here, we report the first crystal structure, solved at 2...
  29. Schwarzer S, Margos G, Overzier E, Fingerle V, Baneth G, Straubinger R. Borrelia persica: In vitro cultivation and characterization via conventional PCR and multilocus sequence analysis of two strains isolated from a cat and ticks from Israel. Ticks Tick Borne Dis. 2015;6:751-7 pubmed publisher
    ..In addition, seven housekeeping genes (clpA, clpX, pepX, pyrG, recG, rplB and uvrA) of this B...
  30. Zhao X, Wang R, Shang Q, Hao H, Li Y, Zhang Y, et al. The new flagella-associated collagen-like proteins ClpB and ClpC of Bacillus amyloliquefaciens FZB42 are involved in bacterial motility. Microbiol Res. 2016;184:25-31 pubmed publisher
    ..However, bacterial localization of the CLPs remains unclear. Here, disrupted strains on all four clp genes (clpA, clpB, clpC and clpD) shown fewer filament than wild-type bacteria in extracellular matrix under scanning electron ..
  31. Krüger A, Engel J, Buettner F, Routier F. Aspergillus fumigatus Cap59-like protein A is involved in α1,3-mannosylation of GPI-anchors. Glycobiology. 2016;26:30-8 pubmed publisher
    ..putative glycosyltransferase involved in capsule formation and virulence, and was thus named Cap59-like protein A (ClpA). Targeted deletion of the clpA gene in A. fumigatus led to absence of α1,3-mannose from mature GPI-anchors...
  32. Wong F, Hagg U. An update on the aetiology of orofacial clefts. Hong Kong Med J. 2004;10:331-6 pubmed
    ..Three of them--namely T-box transcription factor-22 (TBX22), poliovirus receptor like-1 (PVRL1), and interferon regulatory factor-6 (IRF6)--are responsible for causing X-..
  33. Kaewkhampa A, Jotikasthira D, Malaivijitnond S, Kantaputra P. TBX22 mutation associated with cleft lip/palate, hypodontia, and limb anomaly. Cleft Palate Craniofac J. 2012;49:240-4 pubmed publisher
    Mutations in TBX22 are known causes of cleft palate with/without ankyloglossia. We identified a hemizygous missense c.452G>T (p...
  34. Aldred M. Cleft lip and palate: new genetic clues. Trends Mol Med. 2001;7:539-40 pubmed
  35. Sismani C, Donoghue J, Alexandrou A, Karkaletsi M, Christopoulou S, Konstantinidou A, et al. A prenatally ascertained, maternally inherited 14.8 Mb duplication of chromosomal bands Xq13.2-q21.31 associated with multiple congenital abnormalities in a male fetus. Gene. 2013;530:138-42 pubmed publisher
    ..8 Mb in size and includes fourteen genes: SLC16A2, KIAA2022, ABCB7, ZDHHC15, ATRX, MAGT1, ATP7A, PGK1, TBX22, BRWD3, POU3F4, ZNF711, POF1B and CHM...
  36. Laugier Anfossi F, Villard L. Molecular characterization of a new human T-box gene (TBX22) located in xq21.1 encoding a protein containing a truncated T-domain. Gene. 2000;255:289-96 pubmed
    ..We show here that this new gene, called TBX22, is composed of seven exons spanning 8.7 kilobases of genomic DNA in Xq21.1...
  37. Gurramkonda V, Hussain S, Murthy J, Lakkakula B. Two promoter polymorphisms in TBX22 are associated with the risk of NSCLP in Indian women. Clin Dysmorphol. 2015;24:140-3 pubmed publisher
    ..b>TBX22 encodes a T-box containing transcription factor and mutations in this gene are responsible for X-linked cleft ..
  38. Pauws E, Moore G, Stanier P. A functional haplotype variant in the TBX22 promoter is associated with cleft palate and ankyloglossia. J Med Genet. 2009;46:555-61 pubmed publisher
    Mutations in the T-box transcription factor gene TBX22 are found in patients with X-linked cleft palate and ankyloglossia (CPX), and are reported in approximately 5% of all non-syndromic cleft palate patients...
  39. Enkhmandakh B, Bayarsaihan D. Genome-wide Chromatin Mapping Defines AP2? in the Etiology of Craniofacial Disorders. Cleft Palate Craniofac J. 2015;52:135-42 pubmed publisher
    ..in the regulatory regions of many target genes involved in the development of facial tissues including MSX1, IRF6, TBX22, and MAFB...
  40. Brim H, Abu Asab M, Nouraie M, Salazar J, Deleo J, Razjouyan H, et al. An integrative CGH, MSI and candidate genes methylation analysis of colorectal tumors. PLoS ONE. 2014;9:e82185 pubmed publisher
    ..The most amplified markers were CD248, ERCC6, ERGIC3, GNAS, MMP2, NF1, P2RX7, SFRS6, SLC29A1 and TBX22. Most deletions were noted for ADAM29, CHL1, CSMD3, FBXW7, GALNS, MMP2, NF1, PRKD1, SMAD4 and TP53...
  41. Jiang R, Zhao X, Liu R. Non-syndromic cleft palate: analysis of TBX22 exon 5 gene mutation. Arch Med Sci. 2012;8:406-10 pubmed publisher
    This study aimed to investigate the mutation of T-box transcription factor TBX22 exon 5 in children with non-syndromic cleft palate...
  42. Miller J, Chaudhary H, Marsee J. Phylogenetic analysis predicts structural divergence for proteobacterial ClpC proteins. J Struct Biol. 2018;201:52-62 pubmed publisher
    ..Copies of the clpA, clpC, clpE, clpK, and clpL genes are present in all characterized bacteria and their gene products are highly ..
  43. Fu X, Cheng Y, Yuan J, Huang C, Cheng H, Zhou R. Loss-of-function mutation in the X-linked TBX22 promoter disrupts an ETS-1 binding site and leads to cleft palate. Hum Genet. 2015;134:147-58 pubmed publisher
    ..The molecular etiology of the CPO remains unknown. Here, we report a loss-of-function mutation in X-linked TBX22 gene (T-box 22) in a six-generation family of the CPO with obvious phenotypes of both cleft palate and hyper-nasal ..
  44. Packham E, Brook J. T-box genes in human disorders. Hum Mol Genet. 2003;12 Spec No 1:R37-44 pubmed
    ..syndrome/TBX3, and more recently DiGeorge syndrome/TBX1, ACTH deficiency/TBX19 and cleft palate with ankyloglossia/TBX22. This review describes the key features of these disorders and the involvement of T-box genes in their phenotype.
  45. Klockars T, Kyttänen S, Ellonen P. TBX22 and tongue-tie. Cleft Palate Craniofac J. 2012;49:378-9 pubmed publisher
    To resolve if TBX22 mutations cause isolated tongue-tie in the Finnish population. Mutation analysis of the coding region of the TBX22 gene in 50 Finnish isolated tongue-tie patients and 61 control samples...
  46. Pauws E, Peskett E, Boissin C, Hoshino A, Mengrelis K, Carta E, et al. X-linked CHARGE-like Abruzzo-Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations. Clin Genet. 2013;83:352-8 pubmed publisher
    X-linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or ..
  47. Kohli S, Kohli V. A comprehensive review of the genetic basis of cleft lip and palate. J Oral Maxillofac Pathol. 2012;16:64-72 pubmed publisher
    ..Several genes causing syndromic CLP have been discovered. Three of them-T-box transcription factor-22 (TBX22), poliovirus receptor-like-1 (PVRL1), and interferon regulatory factor-6 (IRF6)-are responsible for causing X-..