TBX22

T-box transcription factor 22, the group of T-box transcription factors

Basic information

Region (hg38): X:80014753-80031774

Previous symbols: [ "CPX", "CLPA" ]

Links

ENSG00000122145 ∙ NCBI:50945 ∙ OMIM:300307 ∙ HGNC:11600 ∙ Uniprot:Q9Y458 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cleft palate with or without ankyloglossia, X-linked (Definitive), mode of inheritance: XLR
• Abruzzo-Erickson syndrome (Supportive), mode of inheritance: XL
• cleft palate with or without ankyloglossia, X-linked (Supportive), mode of inheritance: XL
• Abruzzo-Erickson syndrome (Limited), mode of inheritance: XL
• cleft palate with or without ankyloglossia, X-linked (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cleft palate with or without ankyloglossia	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial	11559848; 12374769; 14729838; 15602089; 17846996; 17868388; 21248356; 22784330

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBX22 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX22 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	9	4	14
missense		2	32	2	2	38
nonsense		1				1
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				2		2
non coding			6	7	15	28
Total	0	4	40	18	21

Variants in TBX22

This is a list of pathogenic ClinVar variants found in the TBX22 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-80014787-G-A		Cleft palate with or without ankyloglossia, X-linked	Benign (Jan 13, 2018)
X-80014862-G-A		Cleft palate with or without ankyloglossia, X-linked	Conflicting classifications of pathogenicity (Dec 01, 2022)
X-80014867-A-G		Cleft palate with or without ankyloglossia, X-linked	Likely benign (Jan 12, 2018)
X-80022027-TAC-T			Benign (May 24, 2021)
X-80022027-TACAC-T			Benign (May 17, 2021)
X-80022027-TACACAC-T			Benign (May 16, 2021)
X-80022027-T-TAC			Benign (May 20, 2021)
X-80022027-T-TACAC			Benign (May 19, 2021)
X-80022128-GGTTTT-G			Benign (May 24, 2021)
X-80022261-C-A		Cleft palate with or without ankyloglossia, X-linked • TBX22-related disorder	Likely benign (Apr 27, 2017)
X-80022261-C-G		Cleft palate with or without ankyloglossia, X-linked • TBX22-related disorder	Benign/Likely benign (May 28, 2019)
X-80022270-A-G		TBX22-related disorder	Uncertain significance (Nov 04, 2022)
X-80022289-C-A			Uncertain significance (Nov 17, 2019)
X-80022322-G-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
X-80022324-C-T		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
X-80022325-C-A		Inborn genetic diseases	Uncertain significance (Apr 19, 2024)
X-80022341-C-T		Cleft palate with or without ankyloglossia, X-linked	Benign (Dec 31, 2019)
X-80022375-C-T		Inborn genetic diseases	Uncertain significance (Jul 07, 2022)
X-80022412-G-A		Cleft palate with or without ankyloglossia, X-linked	Uncertain significance (Jan 13, 2018)
X-80022417-A-T			Uncertain significance (Jun 13, 2019)
X-80022435-G-C		Inborn genetic diseases	Uncertain significance (Dec 20, 2021)
X-80022435-G-T		Cleft palate with ankyloglossia	Pathogenic (Oct 01, 2001)
X-80022439-C-T		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
X-80023047-C-A		Cleft palate with or without ankyloglossia, X-linked • TBX22-related disorder	Benign/Likely benign (Jun 01, 2024)
X-80023049-G-T			Uncertain significance (Apr 29, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBX22	protein_coding	protein_coding	ENST00000373294	8	17014

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.977	0.0230	125646	3	6	125655	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.126	204	199	1.03	0.0000145	3425
Missense in Polyphen		55	65.412	0.84083		1072
Synonymous	-0.266	80	77.0	1.04	0.00000611	997
Loss of Function	3.47	1	16.0	0.0625	0.00000117	277

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000295	0.000280
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000722	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000122	0.00000880
Middle Eastern	0.0000722	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable transcriptional regulator involved in developmental processes. This is major determinant crucial to palatogenesis.
• Disease: DISEASE: Abruzzo-Erickson syndrome (ABERS) [MIM:302905]: A disease characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis. {ECO:0000269|PubMed:22784330}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.0586
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.16

Haploinsufficiency Scores

• pHI: 0.0884
• hipred: N
• hipred_score: 0.482
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.610

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tbx22
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; skeleton phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; respiratory system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;multicellular organism development;negative regulation of transcription, DNA-templated
• Cellular component: nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding