• 2
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TBX20 (HGNC:11598) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
T-box transcription factor 20
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
5.83(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.97(Read more about gnomAD pLI score)
LOEUF
0.32(Read more about gnomAD LOEUF score)
Cytoband
7p14.2
Genomic Coordinates
GRCh37/hg19: chr7:35242042-35293711 NCBI Ensembl UCSC
GRCh38/hg38: chr7:35202430-35254100 NCBI Ensembl UCSC
MANE Select Transcript
NM_001077653.2 ENST00000408931.4 (Read more about MANE Select)
Function
Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart. {ECO:0000250}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-13021
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Emerging Evidence for Haploinsufficiency (2)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
05/10/2023

Haploinsufficiency (HI) Score Details

HI Score:
2
HI Evidence Strength:
Emerging Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 17668378
    Kirk et al. (2007) identified a c.583C>T transition in the TBX20 gene in a family in which 6 members in 3 generations had a history of various cardiac anomalies (ASD, mitral valve disease, pulmonary hypertension and cardiomyopathy). The c.583C>T is a nonsense mutation (Q195X) resulting in a truncated TBX20 protein that lacks the C-terminal trans activation and trans repression domains. The c.583C>T transition was not seen in >300 controls. This mutation resulted in reduced transcriptional activation and the inability to induce cardiac tissue formation in frogs and seems to be consistent with loss of function. This group also reports a missense mutation in a family with cardiac anomalies that showed increased DNA binding affinity and possible gain of function mechanism.
  • PUBMED: 30820038
    Luyckx et al (2019) screened 637 unrelated bicuspid aortic valve (BAV) / thoracic aortic aneurysms (TAA) patients for SNVs in the DGCR6 and TBX20 genes. They report a TBX20 nonsense p.(Ser125*) variant in a patient with BAV/TAA. The variant was in a functionally important T-box domain. Inheritance not tested.
  • PUBMED: 27510170
    Zhou et al (2016) sequenced 115 unrelated patients with idiopathic dilated cardiomyopathy and they report on a novel heterozygous nonsense mutation, p.E143*, which they identified in one patient. The mutation was present in 2 other family members with DCM, and also in a female family member with a congenital atrial septal defect. Functional assays using a dual‑luciferase reporter assay system revealed that the truncated TBX20 protein had no transcriptional activity in contrast to the wild‑type.
  • PUBMED: 28553164
    Huang et al (2017) sequenced in 175 unrelated patients with congenital heart disease, and report on a novel heterozygous nonsense p.K274* mutation in a patient with tetralogy of Fallot (TOF). Family studies show the mutation co-segregates with autosomal dominant CHD with complete penetrance. The proband's father, elder brother and son had also TOF. In addition, his father and elder brother had also atrial septal defect, and his niece had persistent truncus arteriosus and ventricular septal defect.
HI Evidence Comments:
Loss of function mutations in TBX20 have been identified in families with atrial septal defect (ASD) and other congenital heart disease. Due to the many TBX20 missense variants reported and lack of whole genes/exonic deletions other disease mechanisms can not be ruled out. Other papers of note: Myasnikov et al (2021, PMID 34202524) report on a three-generation family, with two nonsense mutations in DSG2 and TBX20 cosegregating with a left ventricular non-compaction cardiomyopathy phenotype. Miszalski-Jamka et al (2017, PMID 28798025) report a frameshift variant in association with Left ventricular non-compaction. Liu et al (2008, PMID:18834961) report three patients with cardiac anomalies and missense mutations; two were de novo and one was present in a normal sibling and mother. Functional studies were not performed. Posch et al. (2010, PMID: 19762328) identified a c.374C>G transversion in exon 2 of the TBX20 gene in 3 members of a Lebanese family with heart defects (ASD and cardiac valve defects). The c.374C>G results in a I121M missense mutation. The mutation was not found in 2 unaffected family members, in 680 control alleles, or in 218 control probands from Lebanon. Functional analysis (transcriptional activity via luciferase assay) revealed that the I121M mutant had significantly enhanced transcriptional activity, suggesting that it is a gain-of-function allele.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000007.13) (NC_000007.14)