TBX3

T-box transcription factor 3, the group of T-box transcription factors

Basic information

Region (hg38): 12:114670254-114684175

Previous symbols: [ "UMS" ]

Links

ENSG00000135111 ∙ NCBI:6926 ∙ OMIM:601621 ∙ HGNC:11602 ∙ Uniprot:O15119 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ulnar-mammary syndrome (Definitive), mode of inheritance: AD
• heart conduction disease (Limited), mode of inheritance: AD
• ulnar-mammary syndrome (Strong), mode of inheritance: AD
• ulnar-mammary syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ulnar-Mammary syndrome	AD	Cardiovascular	Cardiac anomalies, including arrhythmias, have been reported, and surveillance may allow early detection and management	Cardiovascular; Dental; Endocrine; Genitourinary; Musculoskeletal; Renal	9207801; 12116211; 12668170; 19938096; 21199695; 28145909

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBX3 gene.

• Ulnar-mammary syndrome (278 variants)
• not provided (74 variants)
• Inborn genetic diseases (32 variants)
• TBX3-related condition (18 variants)
• not specified (7 variants)
• Obesity (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX3 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			4	71	13	88
missense		3	118	6	4	131
nonsense	3					3
start loss						0
frameshift	5	3				8
inframe indel			5			5
splice donor/acceptor (+/-2bp)		1				1
splice region			3	1		4
non coding			47	19	36	102
Total	8	7	174	96	53

Variants in TBX3

This is a list of pathogenic ClinVar variants found in the TBX3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-114670285-A-C		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114670301-GA-G		Ulnar-mammary syndrome	Uncertain significance (Jun 14, 2016)
12-114670331-T-C		Ulnar-mammary syndrome	Benign (Jan 29, 2024)
12-114670459-C-G		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114670464-G-A		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114670501-C-T		Ulnar-mammary syndrome	Benign (Jan 13, 2018)
12-114670529-A-G		Ulnar-mammary syndrome	Benign (Jan 13, 2018)
12-114670556-T-C		Ulnar-mammary syndrome	Benign (Jan 13, 2018)
12-114670577-G-C		Ulnar-mammary syndrome	Benign (Jan 12, 2018)
12-114670617-A-G		Ulnar-mammary syndrome	Benign (Jan 13, 2018)
12-114670654-C-T		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114670660-C-T		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114670755-TAAC-T		Ulnar-mammary syndrome	Likely benign (Jun 14, 2016)
12-114670767-T-C		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114670951-T-C		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114671046-T-C		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114671094-C-T		Ulnar-mammary syndrome	Benign (Jan 13, 2018)
12-114671102-T-C		Ulnar-mammary syndrome	Benign (Jan 13, 2018)
12-114671126-G-C		Ulnar-mammary syndrome	Uncertain significance (Jan 12, 2018)
12-114671270-G-C		Ulnar-mammary syndrome	Benign (Jan 13, 2018)
12-114671312-C-T		Ulnar-mammary syndrome	Uncertain significance (Jan 12, 2018)
12-114671339-T-C		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114671370-A-C		Ulnar-mammary syndrome	Uncertain significance (Jan 13, 2018)
12-114671418-C-G		Ulnar-mammary syndrome	Benign (Jan 12, 2018)
12-114671434-A-G		Ulnar-mammary syndrome	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBX3	protein_coding	protein_coding	ENST00000257566	8	13911

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0109	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.73	343	446	0.769	0.0000256	4767
Missense in Polyphen		95	168.68	0.56321		1900
Synonymous	-0.858	216	201	1.08	0.0000134	1520
Loss of Function	4.00	2	22.4	0.0892	0.00000109	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000380	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor involved in developmental processes. Probably plays a role in limb pattern formation. Acts as a negative regulator of PML function in cellular senescence. {ECO:0000269|PubMed:10468588, ECO:0000269|PubMed:22002537}.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Mesodermal Commitment Pathway;Preimplantation Embryo (Consensus)

Recessive Scores

• pRec: 0.191

Intolerance Scores

• loftool: 0.00413
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.08

Haploinsufficiency Scores

• pHI: 0.932
• hipred: Y
• hipred_score: 0.809
• ghis: 0.653

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.975

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbx3
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; reproductive system 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); embryo phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial 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; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: tbx3a
• Affected structure: fin bud
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;blood vessel development;in utero embryonic development;heart looping;outflow tract morphogenesis;atrioventricular bundle cell differentiation;regulation of transcription by RNA polymerase II;cell aging;positive regulation of cell population proliferation;anterior/posterior axis specification, embryo;animal organ morphogenesis;specification of animal organ position;stem cell population maintenance;limbic system development;male genitalia development;female genitalia development;negative regulation of epithelial cell differentiation;mammary gland development;luteinizing hormone secretion;embryonic forelimb morphogenesis;embryonic hindlimb morphogenesis;forelimb morphogenesis;embryonic digit morphogenesis;negative regulation of apoptotic process;negative regulation of myoblast differentiation;positive regulation of cell cycle;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;follicle-stimulating hormone secretion;mesoderm morphogenesis;roof of mouth development;ventricular septum morphogenesis;branching involved in mammary gland duct morphogenesis;mammary placode formation;cardiac muscle cell fate commitment;sinoatrial node cell development;cellular senescence;positive regulation of stem cell proliferation
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;RNA polymerase II activating transcription factor binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;protein binding;sequence-specific DNA binding