• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TBX5 (HGNC:11604) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
T-box transcription factor 5
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
HOS
Alias symbols
No aliases found
%HI
1.67(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.14(Read more about gnomAD LOEUF score)
Cytoband
12q24.21
Genomic Coordinates
GRCh37/hg19: chr12:114791716-114846247 NCBI Ensembl UCSC
GRCh38/hg38: chr12:114353911-114408442 NCBI Ensembl UCSC
MANE Select Transcript
NM_181486.4 ENST00000405440.7 (Read more about MANE Select)
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:89881... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-21865
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/29/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 24664498
    In 2014, Baban et al. used PCR on an individual with Holt-Oram syndrome to investigate TBX5. Analysis identified a confirmed de novo nonsense variant (p.Arg279Ter) in the proband. Per the authors, “In accord with this data, Western blot analysis performed with two different antibodies against both the amino-terminal and the carboxyl end of TBX5, revealed the complete absence of the shorter isoform of the TBX5 protein (Fig. 1C). These data indicate that this mutant behaves as haploinsufficient allele (Table I).”
  • PUBMED: 10077612
    In 1999, Basson et al. used PCR on individuals with Holt-Oram syndrome to investigate TBX5. The authors identified 2 frameshift variants, 1 nonsense variant, and 1 splice site variant in affected individuals. These variants were confirmed as de novo. In the case of the nonsense variant, the variant was identified in a parent’s germline. Analysis also identified 3 other variants resulting in protein truncation which were familial, but the number of segregations in each case is not noted.
  • PUBMED: PMID: 12818525
    In 2003, Gruenauer-Kloevekorn et al. used PCR and direct sequencing on 2 unrelated families with Holt-Oram syndrome. Analysis identified the same nonsense variant (p.Y136X) resulting in protein truncation in both families. This variant was found in the proband of both families and a total of 4 affected family members across both families. This variant was not identified in unaffected individuals from either family.
HI Evidence Comments:
Mutations in TBX5 cause the autosomal dominant developmental disorder, Holt-Oram syndrome. Additional cases: PMID: 16917909 In 2006, Borozdin et al. used PCR and directing sequencing on 21 unrelated families with Holt-Oram syndrome to identify potential variants in TBX5 and SALL4. Analysis identified 9 variants in TBX5. Per the authors, “seven mutations are truncating (3 nonsense mutations, 4 small deletions), and one splice donor site mutation is expected to result in exon skipping or activation of a cryptic splice site, and as such all mutations are predicted to cause the HOS phenotype via TBX5 haploinsufficiency.” There were 5 familial cases with a total of 6 segregations across the families, not including the probands, and 3 cases which appear to be de novo. PMID: 17534187 In 2007, Debeer et al. used PCR on 27 individuals with Holt-Oram syndrome to identify variants in TBX5. 7 patients had variants in TBX5. The authors identified 5 novel variants including 2 small deletions "(c.1128del1, c.726_730del5) resulting in the production of a truncated protein (Q376Q fs X393 and M242I fs X251, respectively), and a small duplication (K159_L160dup)."

Triplosensitivity (TS) Score Details

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

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)