TBX5
T-box transcription factor 5, the group of T-box transcription factors
Basic information
Region (hg38): 12:114353911-114408442
Previous symbols: [ "HOS" ]
Links
Phenotypes
GenCC
Source:
- Holt-Oram syndrome (Definitive), mode of inheritance: AD
- heart conduction disease (Moderate), mode of inheritance: AD
- Holt-Oram syndrome (Supportive), mode of inheritance: AD
- Holt-Oram syndrome (Definitive), mode of inheritance: AD
- Holt-Oram syndrome (Strong), mode of inheritance: AD
- Holt-Oram syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Holt-Oram syndrome | AD | Cardiovascular | While the condition may be recognizable in the majority, individuals may have cardiac conduction abnormalities even without known cardiac malformations, and surveillance (eg, with electrocardiography) may allow early detection and management | Cardiovascular; Musculoskeletal | 14402857; 8730285; 8911604; 8988165; 8988164; 10077612; 10842287; 12818525; 17366586; 18818409; 20301290 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cardiovascular_phenotype (355 variants)
- Aortic_valve_disease_2 (322 variants)
- Holt-Oram_syndrome (145 variants)
- not_provided (126 variants)
- TBX5-related_disorder (29 variants)
- not_specified (22 variants)
- Primary_dilated_cardiomyopathy (2 variants)
- Congenital_heart_disease_(variable) (2 variants)
- Heart,_malformation_of (2 variants)
- Familial_atrioventricular_septal_defect (1 variants)
- Wolff-Parkinson-White_pattern (1 variants)
- Clubbing_of_fingers (1 variants)
- Abnormal_radial_ray_morphology (1 variants)
- Ventricular_septal_defect (1 variants)
- Small_thenar_eminence (1 variants)
- Mitral_regurgitation (1 variants)
- Atrial_septal_defect,_ostium_secundum_type (1 variants)
- Thumb_deformity (1 variants)
- Atrial_septal_defect_1 (1 variants)
- Blue_nevus (1 variants)
- Atrial_septal_defect (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181486.4. 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 | 154 | 164 | ||||
| missense | 15 | 22 | 255 | 40 | 332 | |
| nonsense | 42 | 53 | ||||
| start loss | 0 | |||||
| frameshift | 69 | 77 | ||||
| splice donor/acceptor (+/-2bp) | 13 | 11 | 24 | |||
| Total | 140 | 47 | 264 | 194 | 5 |
Highest pathogenic variant AF is 0.00000657255
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TBX5 | protein_coding | protein_coding | ENST00000310346 | 8 | 54512 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000463 | 125556 | 0 | 2 | 125558 | 0.00000796 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 234 | 291 | 0.803 | 0.0000153 | 3423 |
| Missense in Polyphen | 49 | 81.032 | 0.6047 | 997 | ||
| Synonymous | -3.44 | 170 | 122 | 1.40 | 0.00000717 | 1004 |
| Loss of Function | 4.35 | 0 | 22.1 | 0.00 | 0.00000103 | 254 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000579 | 0.0000579 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation (PubMed:25725155, PubMed:25963046, PubMed:29174768, PubMed:26917986, PubMed:27035640, PubMed:8988164). Binds to the core DNA motif of NPPA promoter (PubMed:26926761). {ECO:0000269|PubMed:25725155, ECO:0000269|PubMed:25963046, ECO:0000269|PubMed:26917986, ECO:0000269|PubMed:26926761, ECO:0000269|PubMed:27035640, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:8988164}.;
- Disease
- DISEASE: Holt-Oram syndrome (HOS) [MIM:142900]: Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects. {ECO:0000269|PubMed:10077612, ECO:0000269|PubMed:10842287, ECO:0000269|PubMed:12818525, ECO:0000269|PubMed:15735645, ECO:0000269|PubMed:20450920, ECO:0000269|PubMed:8988164, ECO:0000269|PubMed:8988165}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in TBX5 are associated with susceptibility to heart disorders including dilated cardiomyopathy (DCM) and atrial fibrillation (AF). DCM is characterized by ventricular and impaired systolic function, resulting in heart failure and arrhythmia. Patient are at risk of premature death. AF is a common sustained cardiac rhythm disturbance. AF is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:25725155, ECO:0000269|PubMed:25963046, ECO:0000269|PubMed:26917986, ECO:0000269|PubMed:27035640}.;
- Pathway
- Heart Development;Cardiac Progenitor Differentiation;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;YAP1- and WWTR1 (TAZ)-stimulated gene expression
(Consensus)
Recessive Scores
- pRec
- 0.209
Intolerance Scores
- loftool
- rvis_EVS
- -0.55
- rvis_percentile_EVS
- 19.8
Haploinsufficiency Scores
- pHI
- 0.825
- hipred
- Y
- hipred_score
- 0.837
- ghis
- 0.474
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.937
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tbx5
- Phenotype
- growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; skeleton phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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; limbs/digits/tail phenotype;
Zebrafish Information Network
- Gene name
- tbx5a
- Affected structure
- cardiac muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- dissociated from
Gene ontology
- Biological process
- morphogenesis of an epithelium;bundle of His development;atrioventricular valve morphogenesis;endocardial cushion development;cardiac left ventricle formation;ventricular septum development;transcription initiation from RNA polymerase II promoter;cell-cell signaling;pattern specification process;heart development;negative regulation of cell population proliferation;negative regulation of epithelial to mesenchymal transition;lung development;embryonic limb morphogenesis;negative regulation of cell migration;embryonic forelimb morphogenesis;forelimb morphogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of cardioblast differentiation;cardiac muscle cell differentiation;pericardium development;negative regulation of cardiac muscle cell proliferation;positive regulation of cardiac muscle cell proliferation;atrial septum morphogenesis;cell migration involved in coronary vasculogenesis;positive regulation of secondary heart field cardioblast proliferation
- Cellular component
- nucleus;nucleoplasm;cytoplasm;protein-containing complex;protein-DNA complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;sequence-specific DNA binding