• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TBR1 (HGNC:11590) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
T-box brain transcription factor 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
2.97(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.19(Read more about gnomAD LOEUF score)
Cytoband
2q24.2
Genomic Coordinates
GRCh37/hg19: chr2:162272808-162282381 NCBI Ensembl UCSC
GRCh38/hg38: chr2:161416297-161425870 NCBI Ensembl UCSC
MANE Select Transcript
NM_006593.4 ENST00000389554.8 (Read more about MANE Select)
Function
Transcriptional repressor involved in multiple aspects of cortical development, including neuronal migration, laminar and areal identity, and axonal projection (PubMed:25232744, PubMed:30250039). As transcriptional repressor of FEZF2, it blocks the formation of the corticospinal (CS) tract from layer 6 projection neurons, thereby restricting the origin of CS axons specifically to layer 5 neurons (By similarity). {ECO:0000250|UniProtKB:Q64336, ECO:0000269|PubMed:25232744, ECO:0000269|PubMed:30250... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-8312
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
01/24/2018

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Complex Neurodevelopmental Disorder Monarch
HI Evidence:
  • PUBMED: 24458984
    Palumbo et al (2015) identified a de novo deletion by SNP array involving the entire TBR1 gene in an individual with slight dysmorphisms, skeletal alterations, and aggressive-impulsive behavior. Probes over flanking genes were not deviating.
  • PUBMED: 25849321
    Li et al (2016) used WES/WGS to identify a de novo frameshift variant in exon 1 of 6 of TBR1 in a patient with autism spectrum disorder and another de novo TBR1 frameshift in exon 6 (at amino acid 532) in a patient with intellectual disability.
  • PUBMED: 23160955
    O'Roak et al (2012) sequenced 44 candidate genes in 2,446 probands with autism spectrum disorder. They identified a de novo frameshift in exon 1 of TBR1 in one patient. This patient also had a rare, paternally-inherited duplication of at least 315 kb. Another patient was found to have a de novo frameshift in exon 4. Potentially de novo events were confirmed by Sanger sequencing in this study.
HI Evidence Comments:
PMID 25232744: Deriziotis et al performed functional studies on de novo TBR1 variants. One early frameshift was studied, which produced results consistent with loss-of-function. However, per the assays performed expression of the protein product was not reduced. PMID 24896178: c.1588_1594dupGGCTGCA frameshift at amino acid 532 reported as a de novo variant in a patient with intellectual disabiltiy. Appears to be the same variant reported by Li et al (2016).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No duplications involving only the TBR1 gene reported.

Genomic View

Select assembly: (NC_000002.11) (NC_000002.12)