TBR1

T-box brain transcription factor 1, the group of T-box transcription factors

Basic information

Region (hg38): 2:161416296-161425870

Links

ENSG00000136535 ∙ NCBI:10716 ∙ OMIM:604616 ∙ HGNC:11590 ∙ Uniprot:Q16650 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism (Definitive), mode of inheritance: AD
• occipital pachygyria and polymicrogyria (Supportive), mode of inheritance: AR
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with autism and speech delay	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	25232744; 29288087; 30250039; 30268909

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBR1 gene.

• not provided (81 variants)
• Inborn genetic diseases (60 variants)
• Autism, susceptibility to, 5 (34 variants)
• Autistic behavior;Moderate global developmental delay (7 variants)
• Intellectual disability (6 variants)
• Neurodevelopmental disorder (4 variants)
• Autistic behavior;Severe global developmental delay (4 variants)
• See cases (3 variants)
• TBR1-related condition (3 variants)
• not specified (2 variants)
• Moderate global developmental delay (2 variants)
• Severe global developmental delay (2 variants)
• Delayed fine motor development;Moderate global developmental delay;Attention deficit hyperactivity disorder;Autistic behavior (1 variants)
• Moderate global developmental delay;Autistic behavior (1 variants)
• Focal cortical dysplasia;Severe global developmental delay;Gait ataxia;Seizure;Delayed fine motor development (1 variants)
• Delayed fine motor development;Seizure;Aggressive behavior;Gait disturbance;Severe global developmental delay (1 variants)
• Limb myoclonus;Aggressive behavior;Severe global developmental delay;Autistic behavior (1 variants)
• Severe global developmental delay;Hypoplasia of the frontal lobes;Gait ataxia;Delayed fine motor development (1 variants)
• Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (1 variants)
• Marfanoid habitus and intellectual disability (1 variants)
• Seizure (1 variants)
• History of neurodevelopmental disorder (1 variants)
• Atypical behavior;Moderate global developmental delay;Aplasia/Hypoplasia of the corpus callosum;Seizure (1 variants)
• Abnormal brainstem MRI signal intensity;Severe global developmental delay;Autistic behavior;Delayed fine motor development (1 variants)
• 10 conditions (1 variants)
• Moderate global developmental delay;Attention deficit hyperactivity disorder;Autistic behavior;Aggressive behavior (1 variants)
• Severe global developmental delay;Autistic behavior (1 variants)
• Autistic behavior (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	21	3	25
missense	2	12	100	9		123
nonsense	1	7				8
start loss						0
frameshift	7	14				21
inframe indel		1			1	2
splice donor/acceptor (+/-2bp)	1	1				2
splice region			5	1		6
non coding					1	1
Total	11	35	101	30	5

Variants in TBR1

This is a list of pathogenic ClinVar variants found in the TBR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-161416427-GC-G			Likely pathogenic (Sep 01, 2023)
2-161416464-C-G		Inborn genetic diseases	Benign (Dec 31, 2019)
2-161416467-T-C		Inborn genetic diseases	Likely benign (Nov 26, 2019)
2-161416483-C-A		Autism, susceptibility to, 5	Uncertain significance (Apr 29, 2021)
2-161416483-C-G		Inborn genetic diseases	Likely benign (Jun 12, 2017)
2-161416504-C-A			Uncertain significance (Sep 01, 2023)
2-161416516-G-A			Uncertain significance (Apr 14, 2022)
2-161416522-C-T			Uncertain significance (Jul 07, 2020)
2-161416557-T-A			Uncertain significance (Mar 10, 2023)
2-161416573-AT-A		Inborn genetic diseases	Pathogenic (Apr 14, 2022)
2-161416574-T-C		Autism, susceptibility to, 5	Uncertain significance (Apr 20, 2021)
2-161416577-C-G			Uncertain significance (Oct 07, 2022)
2-161416583-G-T		Intellectual disability	Uncertain significance (Sep 10, 2020)
2-161416602-TACAG-T		See cases	Pathogenic (Jul 28, 2022)
2-161416622-C-G			Uncertain significance (Feb 01, 2020)
2-161416625-A-G		Inborn genetic diseases	Uncertain significance (Aug 26, 2019)
2-161416627-G-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
2-161416637-G-A		Inborn genetic diseases	Uncertain significance (Feb 13, 2017)
2-161416641-C-A			Uncertain significance (Nov 03, 2021)
2-161416653-T-C		Inborn genetic diseases	Likely benign (Apr 20, 2017)
2-161416661-C-G		Autism, susceptibility to, 5	Uncertain significance (Aug 16, 2022)
2-161416666-G-T			Likely benign (Jan 01, 2024)
2-161416671-G-A			Likely benign (Mar 19, 2018)
2-161416687-C-T		Inborn genetic diseases	Uncertain significance (May 31, 2023)
2-161416688-T-A			Uncertain significance (Dec 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBR1	protein_coding	protein_coding	ENST00000389554	6	9777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000992	125456	0	1	125457	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.64	172	368	0.467	0.0000169	4420
Missense in Polyphen		66	167.09	0.39499		1943
Synonymous	0.687	145	156	0.930	0.00000745	1373
Loss of Function	4.39	1	24.4	0.0409	0.00000112	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000328
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable transcriptional regulator involved in developmental processes. Required for normal brain development.

Recessive Scores

• pRec: 0.380

Intolerance Scores

• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.932
• hipred: Y
• hipred_score: 0.851
• ghis: 0.584

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.980

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tbr1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: conditioned taste aversion;brain development;specification of animal organ identity;amygdala development;commitment of neuronal cell to specific neuron type in forebrain;cerebral cortex development;hindbrain development;positive regulation of transcription by RNA polymerase II;regulation of axon guidance
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;protein kinase binding;identical protein binding