• 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TBX2 (HGNC:11597) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
T-box transcription factor 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
5.16(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.99(Read more about gnomAD pLI score)
LOEUF
0.25(Read more about gnomAD LOEUF score)
Cytoband
17q23.2
Genomic Coordinates
GRCh37/hg19: chr17:59477204-59486827 NCBI Ensembl UCSC
GRCh38/hg38: chr17:61399843-61409466 NCBI Ensembl UCSC
MANE Select Transcript
NM_005994.4 ENST00000240328.4 (Read more about MANE Select)
Function
Transcription factor which acts as a transcriptional repressor (PubMed:11111039, PubMed:11062467, PubMed:12000749, PubMed:22844464, PubMed:30599067). May also function as a transcriptional activator (By similarity). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence, or a half-site, which are present in the regulatory region of several genes (PubMed:11111039, PubMed:12000749, PubMed:22844464, PubMed:30599067). Required for cardiac atrioventricular canal formation (PubMed:29726... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-2974
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
08/08/2018

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 28372585
    Qian et al (2017) reported a frameshift mutation in a patient with Tetralogy of Fallot (TOF) and atrioventricular septal defect within cohort of 106 patients with TOF tested for genetic causes using a 29 gene sequencing panel.
HI Evidence Comments:
Thus far, a single patient with a frameshift (presumed LOF) variant of TBX2 has been reported. Therefore the haploinsufficiency score is 1. Additional relevant literature is summarized below: PMID 29726930: Liu et al. 2018 reported four patients with craniofacial dysmorphisms, cardiac anomalies, skeletal anomalies, immune deficiency, endocrine anomalies and developmental delay with missense mutations in TBX2. Patients included one family with two siblings and a more mildly affected mother as well as one patient with a de novo mutation. Functional studies show reduced activity of transcriptional repressor, reduced protein levels and suggest partial loss of function alleles. PMID 23727221: Pang et al (2013) identified four novel heterozygous DSVs (DNA sequence variants) within the TBX2 gene promoter in VSD (ventricular septal defects) patients, which significantly decreased transcriptional activities of the TBX2 gene promoter. These results suggested that these DNA sequence variants may change TBX2 levels, contributing to VSD etiology.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Focal duplication of TBX2 has not been reported in association with clinical phenotypes. Therefore the triplosensitivity score is 0. Additional relevant literature is summarized below: PMID 20635360: Radio et al (2010) reported a four year old male patient with mild intellectual disability, minor dysmorphic features and skeletal anomalies, complex heart defect, laryngomalacia, cerebellar, pons and medulla hypoplasia, and Duane anomaly. Patient was found to have a de novo 131 kb duplication including all of TBX2 as well as C17orf82, and a portion of BCAS3. Authors propose heart malformation and mild digital anomalies in the patient could be related to gene overexpression.

Genomic View

Select assembly: (NC_000017.10) (NC_000017.11)