TBR1 |
- 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
- 0.25(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
ClinGen Curation ID:
CCID:007975
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)