• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TBX3 (HGNC:11602) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
T-box transcription factor 3
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
UMS
Alias symbols
TBX3-ISO, XHL
%HI
3.05(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.99(Read more about gnomAD pLI score)
LOEUF
0.28(Read more about gnomAD LOEUF score)
Cytoband
12q24.21
Genomic Coordinates
GRCh37/hg19: chr12:115108060-115121980 NCBI Ensembl UCSC
GRCh38/hg38: chr12:114670255-114684175 NCBI Ensembl UCSC
MANE Select Transcript
NM_005996.4 ENST00000349155.7 (Read more about MANE Select)
Function
Transcriptional repressor involved in developmental processes (PubMed:10468588). 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:12000749). Probably plays a role in limb pattern formation (PubMed:10468588). Required for mammary placode induction, and maintenance of the mammary buds during development (By similarity). Involved in branching morphogenesis in both developing lungs and adult ma... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-30692
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
09/23/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 12668170
    Wollnik et al. (2002) reported a frameshift pathogenic variant (TBX3: c.88_89insA , M30fsX110) segregation among 10 family members spanning 3 generations in a large Turkish family affected with ulnar-mammary syndrome. The phenotypic expression of the disease was highly variable among the affected family members.
  • PUBMED: 28145909
    Tanteles et al. (2017) identified a heterozygous pathogenic variant (TBX3: c.1423C>T, p.Glu475Ter) in a Cypriot family in which twin brothers and their father had ulnar-mammary syndrome. The variant segregated with the disorder in the family. The twins showed classic features of the disorder, whereas their father was mildly affected.
  • PUBMED: 12116211
    Sasaki et al. (2002) identified a heterozygous pathogenic variant (TBX3: TBX3: c.817A>T, p.Lys273Ter) in a Japanese mother and her 2 sons with ulnar-mammary syndrome, micropenis with or without cryptorchidism, and hypoplastic nipples in the brothers; and hypoplastic mammary glands and nipples, poor perspiration, and bicornuate uterus in the mother.
HI Evidence Comments:
Haploinsufficiency of TBX3 has been associated with ulnar-mammary syndrome (UMS), an autosomal dominant pleotropic disorder characterized with mammary and apocrine gland hypoplasia, upper limb defects, malformations of areola, dental structures, heart and genitalia. Variable expressivity has been well-documented for this syndrome. Additional Evidence: Khan et al, 2020 (PMID:31669645) summarized total eighteen UMS causing pathogenic variants of TBX3 gene including 5 nonsense, 8 frameshift (due to deletion and insertion), 3 missense and 2 splice site mutations. Among all of these, fifteen variants present apparently haploinsufficiency.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Although somatic PBX3 overexpression has been associated with tumor formation, angiogenesis and metastasis in several cancer type including breast cancer, colorectal cancer, etc. due to its tumor suppressor role. Currently there is no available evidence for TBX3 triplosensitivity in the hereditary disease.

Genomic View

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