TBX1
T-box transcription factor 1, the group of T-box transcription factors
Basic information
Region (hg38): 22:19756703-19783593
Previous symbols: [ "VCF" ]
Links
Phenotypes
GenCC
Source:
- DiGeorge syndrome (Definitive), mode of inheritance: AD
- 22q11.2 deletion syndrome (Supportive), mode of inheritance: AD
- velocardiofacial syndrome (Strong), mode of inheritance: AD
- conotruncal heart malformations (Definitive), mode of inheritance: AD
- conotruncal heart malformations (Strong), mode of inheritance: AD
- DiGeorge syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Conotruncal anomaly face syndrome; Tetralogy of Fallot | AD | Cardiovascular | The conditions can include congenital cardiac anomalies, and awareness may allow early identification and management | Cardiovascular; Craniofacial; Neurologic | 14585638; 16684884; 17273972; 17377518; 19948535; 20937753 |
ClinVar
This is a list of variants' phenotypes submitted to
- DiGeorge_syndrome (780 variants)
- Cardiovascular_phenotype (385 variants)
- not_provided (198 variants)
- TBX1-related_disorder (53 variants)
- not_specified (42 variants)
- Velocardiofacial_syndrome (29 variants)
- Tetralogy_of_Fallot (25 variants)
- Conotruncal_heart_malformations (21 variants)
- Inborn_genetic_diseases (2 variants)
- Conotruncal_anomaly_face_syndrome (2 variants)
- Hypoplastic_left_heart_syndrome (1 variants)
- KBG_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379200.1. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 9 | 307 | 1 | 317 | ||
| missense | 2 | 6 | 483 | 28 | 2 | 521 |
| nonsense | 10 | 4 | 4 | 18 | ||
| start loss | 0 | |||||
| frameshift | 22 | 4 | 5 | 31 | ||
| splice donor/acceptor (+/-2bp) | 3 | 5 | 1 | 9 | ||
| Total | 37 | 19 | 502 | 335 | 3 |
Highest pathogenic variant AF is 0.0000027212438
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TBX1 | protein_coding | protein_coding | ENST00000332710 | 8 | 26891 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 125734 | 0 | 2 | 125736 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.735 | 189 | 220 | 0.860 | 0.0000124 | 3128 |
| Missense in Polyphen | 85 | 106.82 | 0.7957 | 1131 | ||
| Synonymous | -3.55 | 139 | 95.0 | 1.46 | 0.00000597 | 1022 |
| Loss of Function | 3.07 | 2 | 14.7 | 0.136 | 7.77e-7 | 190 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000291 | 0.0000291 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Probable transcriptional regulator involved in developmental processes. Is required for normal development of the pharyngeal arch arteries (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Note=Haploinsufficiency of the TBX1 gene is responsible for most of the physical malformations present in DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). DGS is characterized by the association of several malformations: hypoplastic thymus and parathyroid glands, congenital conotruncal cardiopathy, and a subtle but characteristic facial dysmorphology. VCFS is marked by the association of congenital conotruncal heart defects, cleft palate or velar insufficiency, facial dysmorpholgy and learning difficulties. It is now accepted that these two syndromes represent two forms of clinical expression of the same entity manifesting at different stages of life.; DISEASE: DiGeorge syndrome (DGS) [MIM:188400]: A congenital syndrome characterized by a wide spectrum of characteristics including parathyroid hypoplasia resulting in hypocalcemia, thymic hypoplasia resulting in T-cell immunodeficiency, defects in the outflow tract of the heart, and craniofacial anomalies. Disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches can account for the phenotype. {ECO:0000269|PubMed:14585638}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Velocardiofacial syndrome (VCFS) [MIM:192430]: A syndrome characterized by abnormal pharyngeal arch development that results in defective development of the parathyroid glands, thymus, and conotruncal region of the heart. The phenotype is highly variable, with no single clinical feature present in every patient. Affected individuals may present with structural or functional palatal abnormalities, cardiac defects, unique facial characteristics, hypernasal speech, hypotonia, and defective thymic development associated with impaired immune function. In addition, affected individuals may present with learning disabilities, overt developmental delay, and psychiatric disorders. {ECO:0000269|PubMed:14585638, ECO:0000269|PubMed:17273972}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Heart Development;Mesodermal Commitment Pathway;FTO Obesity Variant Mechanism
(Consensus)
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.969
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Zebrafish Information Network
- Gene name
- tbx1
- Affected structure
- cardiac muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- angiogenesis;blood vessel development;cell fate specification;neural crest cell migration;positive regulation of protein phosphorylation;lymph vessel development;positive regulation of mesenchymal cell proliferation;heart morphogenesis;outflow tract septum morphogenesis;outflow tract morphogenesis;regulation of transcription by RNA polymerase II;determination of left/right symmetry;pattern specification process;mesoderm development;heart development;muscle organ development;sensory perception of sound;cell population proliferation;positive regulation of cell population proliferation;anterior/posterior pattern specification;vagus nerve morphogenesis;epithelial cell differentiation;thyroid gland development;social behavior;aorta morphogenesis;ear morphogenesis;inner ear morphogenesis;outer ear morphogenesis;middle ear morphogenesis;odontogenesis of dentin-containing tooth;muscle cell fate commitment;positive regulation of MAPK cascade;tongue morphogenesis;cellular response to fibroblast growth factor stimulus;negative regulation of cell differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;retinoic acid receptor signaling pathway;blood vessel morphogenesis;thymus development;muscle organ morphogenesis;embryonic cranial skeleton morphogenesis;embryonic viscerocranium morphogenesis;semicircular canal morphogenesis;artery morphogenesis;positive regulation of epithelial cell proliferation;parathyroid gland development;soft palate development;pharyngeal system development;face morphogenesis;muscle tissue morphogenesis;coronary artery morphogenesis;enamel mineralization;cellular response to retinoic acid;cochlea morphogenesis;mesenchymal cell apoptotic process;regulation of animal organ morphogenesis;positive regulation of tongue muscle cell differentiation;negative regulation of mesenchymal cell apoptotic process
- Cellular component
- nucleus
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein homodimerization activity;sequence-specific DNA binding