TBXT

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

Basic information

Region (hg38): 6:166157655-166168700

Previous symbols: [ "T" ]

Links

ENSG00000164458 ∙ NCBI:6862 ∙ OMIM:601397 ∙ HGNC:11515 ∙ Uniprot:O15178 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chordoma (Strong), mode of inheritance: AD
• sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chordoma	AD	Oncologic	Surveillance for neoplasms could potentially be beneficial in order to allow early detection and treatment	Gastrointestinal; Musculoskeletal; Oncologic; Renal	8733136; 10204846; 10332959; 10817656; 12116228; 15449172; 19801981; 23064415; 24253444

ClinVar

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

• Inborn genetic diseases (20 variants)
• not provided (10 variants)
• Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome (2 variants)
• not specified (1 variants)
• Microcephaly-thin corpus callosum-intellectual disability syndrome (1 variants)
• Neural tube defect (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBXT 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					2	2
missense			24	3	2	29
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	1	25	3	4

Variants in TBXT

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

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

Position	Type	Phenotype	Significance	ClinVar
6-166158401-T-TGGCCGC			Uncertain significance (Dec 01, 2023)
6-166158407-C-T		not specified	Likely benign (Feb 06, 2023)
6-166158412-G-T		not specified	Uncertain significance (Aug 30, 2021)
6-166158425-G-C		not specified	Uncertain significance (Jun 21, 2022)
6-166158436-G-A		not specified	Uncertain significance (Feb 13, 2015)
6-166158447-C-T			Benign (Oct 16, 2018)
6-166158457-G-A		not specified	Uncertain significance (Feb 27, 2024)
6-166158460-T-C		not specified	Uncertain significance (Apr 07, 2023)
6-166158516-G-A		TBXT-related disorder	Likely benign (Mar 07, 2019)
6-166158517-T-C		TBXT-related disorder	Benign (May 02, 2019)
6-166158524-C-A			Uncertain significance (Jul 26, 2017)
6-166158524-C-T			Benign (Dec 31, 2019)
6-166158544-G-A		not specified	Uncertain significance (Mar 07, 2024)
6-166158558-G-A		TBXT-related disorder	Likely benign (Jul 30, 2019)
6-166160758-G-A		Neural tube defects, susceptibility to	risk factor (Nov 01, 2004)
6-166160857-G-T		TBXT-related disorder	Likely benign (Mar 05, 2019)
6-166160858-G-A		TBXT-related disorder	Benign/Likely benign (May 02, 2019)
6-166160871-C-T		not specified	Likely benign (Sep 27, 2021)
6-166160936-G-A		not specified	Uncertain significance (Jan 16, 2024)
6-166160974-G-A			Benign (Dec 31, 2019)
6-166162494-C-T		not specified	Uncertain significance (Jan 10, 2022)
6-166162495-G-A		not specified	Uncertain significance (Dec 16, 2022)
6-166162503-C-T		not specified	Uncertain significance (Jul 14, 2022)
6-166162509-G-C		not specified	Uncertain significance (Jan 30, 2024)
6-166162537-A-AG			Likely pathogenic (Jun 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBXT	protein_coding	protein_coding	ENST00000296946	8	11045

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0243	0.973	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.984	207	251	0.825	0.0000139	2837
Missense in Polyphen		43	70.443	0.61043		896
Synonymous	0.232	106	109	0.972	0.00000724	878
Loss of Function	2.64	6	18.1	0.331	7.88e-7	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000335	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the transcriptional regulation of genes required for mesoderm formation and differentiation. Binds to a palindromic site (called T site) and activates gene transcription when bound to such a site. {ECO:0000250|UniProtKB:P20293}.
• Disease: DISEASE: Chordoma (CHDM) [MIM:215400]: Rare, clinically malignant tumors derived from notochordal remnants. They occur along the length of the spinal axis, predominantly in the sphenooccipital, vertebral and sacrococcygeal regions. They are characterized by slow growth, local destruction of bone, extension into adjacent soft tissues and rarely, distant metastatic spread. {ECO:0000269|PubMed:19801981}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to development of chordomas is due to a T gene duplication.; DISEASE: Sacral agenesis with vertebral anomalies (SAVA) [MIM:615709]: A disorder characterized by abnormalities of the spine, including sacral agenesis, abnormal ossification of all vertebral bodies, and a persistent notochordal canal during development. {ECO:0000269|PubMed:24253444}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cardiac Progenitor Differentiation;Regulation of nuclear beta catenin signaling and target gene transcription;Validated transcriptional targets of deltaNp63 isoforms (Consensus)

Recessive Scores

• pRec: 0.276

Intolerance Scores

• rvis_EVS: 0.69
• rvis_percentile_EVS: 85.18

Haploinsufficiency Scores

• pHI: 0.295
• hipred: Y
• hipred_score: 0.712

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: T
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region 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); digestive/alimentary 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); limbs/digits/tail phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); normal phenotype; reproductive system phenotype

Zebrafish Information Network

• Gene name: tbxta
• Affected structure: Rohon-Beard neuron
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;vasculogenesis;somitogenesis;neural plate morphogenesis;neural tube closure;heart morphogenesis;positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation;signal transduction;penetration of zona pellucida;mesoderm development;mesoderm migration involved in gastrulation;positive regulation of cell population proliferation;anterior/posterior axis specification, embryo;notochord formation;signal transduction involved in regulation of gene expression;BMP signaling pathway;post-anal tail morphogenesis;negative regulation of DNA-binding transcription factor activity;embryonic skeletal system development;canonical Wnt signaling pathway;bone morphogenesis;SMAD protein signal transduction;determination of heart left/right asymmetry;cellular response to retinoic acid;primitive streak formation
• Cellular component: nuclear chromatin;nucleus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer 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 factor activity