TBX1

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

Basic information

Region (hg38): 22:19756702-19783593

Previous symbols: [ "VCF" ]

Links

ENSG00000184058 ∙ NCBI:6899 ∙ OMIM:602054 ∙ HGNC:11592 ∙ Uniprot:O43435 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• DiGeorge syndrome (Definitive), mode of inheritance: AD
• 22q11.2 deletion syndrome (Supportive), mode of inheritance: AD
• velocardiofacial syndrome (Strong), mode of inheritance: AD
• conotruncal heart malformations (Definitive), mode of inheritance: AD
• conotruncal heart malformations (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Conotruncal anomaly face syndrome; Tetralogy of Fallot	AD	Cardiovascular	The conditions can include congenital cardiac anomalies, and awareness may allow early identification and management	Cardiovascular; Craniofacial; Neurologic	14585638; 16684884; 17273972; 17377518; 19948535; 20937753

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBX1 gene.

• DiGeorge syndrome (563 variants)
• Cardiovascular phenotype (236 variants)
• not provided (179 variants)
• not specified (23 variants)
• TBX1-related condition (14 variants)
• Inborn genetic diseases (13 variants)
• Tetralogy of Fallot (5 variants)
• Velocardiofacial syndrome (3 variants)
• Conotruncal heart malformations;Velocardiofacial syndrome;Tetralogy of Fallot;DiGeorge syndrome (3 variants)
• Conotruncal heart malformations;Velocardiofacial syndrome;DiGeorge syndrome;Tetralogy of Fallot (2 variants)
• Conotruncal heart malformations (2 variants)
• Tetralogy of Fallot;Conotruncal heart malformations;Velocardiofacial syndrome;DiGeorge syndrome (2 variants)
• Conotruncal heart malformations;DiGeorge syndrome;Velocardiofacial syndrome;Tetralogy of Fallot (2 variants)
• Velocardiofacial syndrome;Conotruncal heart malformations;DiGeorge syndrome;Tetralogy of Fallot (2 variants)
• Tetralogy of Fallot;Velocardiofacial syndrome;DiGeorge syndrome (1 variants)
• Conotruncal heart malformations;Tetralogy of Fallot;DiGeorge syndrome;Velocardiofacial syndrome (1 variants)
• Hypoplastic left heart syndrome (1 variants)
• DiGeorge syndrome;Velocardiofacial syndrome;Tetralogy of Fallot;Conotruncal heart malformations (1 variants)
• Velocardiofacial syndrome;Tetralogy of Fallot;Conotruncal heart malformations;DiGeorge syndrome (1 variants)
• Seizure (1 variants)
• DiGeorge syndrome;Tetralogy of Fallot;Velocardiofacial syndrome;Conotruncal heart malformations (1 variants)
• Velocardiofacial syndrome;DiGeorge syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX1 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			7	205	7	219
missense		2	337	15	2	356
nonsense	6	1	2			9
start loss			1			1
frameshift	14	3	5			22
inframe indel			40	7	1	48
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			15	12	3	30
non coding			4	57	22	83
Total	21	8	397	284	32

Variants in TBX1

This is a list of pathogenic ClinVar variants found in the TBX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-19759380-A-T			Benign (Mar 03, 2015)
22-19759510-C-G			Benign (Mar 01, 2024)
22-19759519-C-T			Benign (Jul 26, 2018)
22-19759559-G-C			Benign (Mar 03, 2015)
22-19759559-G-TC			Benign (Mar 03, 2015)
22-19759605-C-T		not specified • DiGeorge syndrome	Benign/Likely benign (Mar 01, 2024)
22-19759628-A-C		not specified	Uncertain significance (Mar 12, 2024)
22-19759638-GCAGGGATGCA-G		DiGeorge syndrome	Uncertain significance (Sep 17, 2022)
22-19759641-G-A		Cardiovascular phenotype	Likely benign (May 26, 2022)
22-19759657-C-T		Cardiovascular phenotype	Uncertain significance (Apr 28, 2023)
22-19759658-C-A		DiGeorge syndrome	Conflicting classifications of pathogenicity (Dec 26, 2023)
22-19759658-C-T		DiGeorge syndrome • Cardiovascular phenotype	Likely benign (Mar 27, 2023)
22-19759661-C-G		Cardiovascular phenotype	Likely benign (Dec 24, 2021)
22-19759669-A-T		Cardiovascular phenotype	Uncertain significance (Jul 12, 2021)
22-19759671-A-G		DiGeorge syndrome	Uncertain significance (Jul 12, 2020)
22-19759679-T-A		DiGeorge syndrome	Likely pathogenic (Aug 24, 2023)
22-19759682-G-A			Uncertain significance (Jan 26, 2018)
22-19759683-C-T		DiGeorge syndrome	Uncertain significance (Apr 01, 2024)
22-19759689-G-A		DiGeorge syndrome	Likely benign (Sep 13, 2023)
22-19759694-T-A		DiGeorge syndrome	Likely benign (Dec 11, 2023)
22-19759695-G-C		DiGeorge syndrome	Likely benign (Aug 24, 2023)
22-19759960-A-AG			Likely benign (Jan 09, 2020)
22-19759962-G-C			Benign (Jul 07, 2018)
22-19759963-G-T			Likely benign (Aug 10, 2018)
22-19759964-G-A			Likely benign (Aug 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBX1	protein_coding	protein_coding	ENST00000332710	8	26891

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.837	0.163	125734	0	2	125736	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.735	189	220	0.860	0.0000124	3128
Missense in Polyphen		85	106.82	0.7957		1131
Synonymous	-3.55	139	95.0	1.46	0.00000597	1022
Loss of Function	3.07	2	14.7	0.136	7.77e-7	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable transcriptional regulator involved in developmental processes. Is required for normal development of the pharyngeal arch arteries (By similarity). {ECO:0000250}.
• Disease: DISEASE: Note=Haploinsufficiency of the TBX1 gene is responsible for most of the physical malformations present in DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). DGS is characterized by the association of several malformations: hypoplastic thymus and parathyroid glands, congenital conotruncal cardiopathy, and a subtle but characteristic facial dysmorphology. VCFS is marked by the association of congenital conotruncal heart defects, cleft palate or velar insufficiency, facial dysmorpholgy and learning difficulties. It is now accepted that these two syndromes represent two forms of clinical expression of the same entity manifesting at different stages of life.; DISEASE: DiGeorge syndrome (DGS) [MIM:188400]: A congenital syndrome characterized by a wide spectrum of characteristics including parathyroid hypoplasia resulting in hypocalcemia, thymic hypoplasia resulting in T-cell immunodeficiency, defects in the outflow tract of the heart, and craniofacial anomalies. Disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches can account for the phenotype. {ECO:0000269|PubMed:14585638}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Velocardiofacial syndrome (VCFS) [MIM:192430]: A syndrome characterized by abnormal pharyngeal arch development that results in defective development of the parathyroid glands, thymus, and conotruncal region of the heart. The phenotype is highly variable, with no single clinical feature present in every patient. Affected individuals may present with structural or functional palatal abnormalities, cardiac defects, unique facial characteristics, hypernasal speech, hypotonia, and defective thymic development associated with impaired immune function. In addition, affected individuals may present with learning disabilities, overt developmental delay, and psychiatric disorders. {ECO:0000269|PubMed:14585638, ECO:0000269|PubMed:17273972}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Heart Development;Mesodermal Commitment Pathway;FTO Obesity Variant Mechanism (Consensus)

Haploinsufficiency Scores

• pHI: 0.326
• hipred: Y
• hipred_score: 0.809
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbx1
• Phenotype: skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; 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); digestive/alimentary phenotype; normal phenotype; 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: tbx1
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: angiogenesis;blood vessel development;cell fate specification;neural crest cell migration;positive regulation of protein phosphorylation;lymph vessel development;positive regulation of mesenchymal cell proliferation;heart morphogenesis;outflow tract septum morphogenesis;outflow tract morphogenesis;regulation of transcription by RNA polymerase II;determination of left/right symmetry;pattern specification process;mesoderm development;heart development;muscle organ development;sensory perception of sound;cell population proliferation;positive regulation of cell population proliferation;anterior/posterior pattern specification;vagus nerve morphogenesis;epithelial cell differentiation;thyroid gland development;social behavior;aorta morphogenesis;ear morphogenesis;inner ear morphogenesis;outer ear morphogenesis;middle ear morphogenesis;odontogenesis of dentin-containing tooth;muscle cell fate commitment;positive regulation of MAPK cascade;tongue morphogenesis;cellular response to fibroblast growth factor stimulus;negative regulation of cell differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;retinoic acid receptor signaling pathway;blood vessel morphogenesis;thymus development;muscle organ morphogenesis;embryonic cranial skeleton morphogenesis;embryonic viscerocranium morphogenesis;semicircular canal morphogenesis;artery morphogenesis;positive regulation of epithelial cell proliferation;parathyroid gland development;soft palate development;pharyngeal system development;face morphogenesis;muscle tissue morphogenesis;coronary artery morphogenesis;enamel mineralization;cellular response to retinoic acid;cochlea morphogenesis;mesenchymal cell apoptotic process;regulation of animal organ morphogenesis;positive regulation of tongue muscle cell differentiation;negative regulation of mesenchymal cell apoptotic process
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein homodimerization activity;sequence-specific DNA binding