TBR1

Chr 2

T-box brain transcription factor 1

Also known as: AUTS5, IDDAS, TBR-1, TES-56

NCBI Gene: 10716ENSG00000136535UniProt: Q16650

This gene is a member of a conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of numerous developmental processes. In mouse, the ortholog of this gene is expressed in the cerebral cortex, hippocampus, amygdala and olfactory bulb and is thought to play an important role in neuronal migration and axonal projection. In mouse, the C-terminal region of this protein was found to be necessary and sufficient for association with the guanylate kinase domain of calcium/calmodulin-dependent serine protein kinase. [provided by RefSeq, Dec 2015]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder with autism and speech delay

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
42
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — TBR1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.19LOEUF
pLI 0.999
Z-score 4.39
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.64Z-score
OE missense 0.47 (0.41–0.53)
172 obs / 368.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.04 (0.01–0.19)
0≤0.351.4
Missense OE?0.47 (0.41–0.53)
0≤0.61.4
Synonymous OE?0.93
0≤1.21.6
LoF obs/exp: 1 / 24.5Missense obs/exp: 172 / 368.4Syn Z: 0.69

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TBR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients