TBX6

T-box transcription factor 6, the group of T-box transcription factors

Basic information

Region (hg38): 16:30085793-30091924

Links

ENSG00000149922 ∙ NCBI:6911 ∙ OMIM:602427 ∙ HGNC:11605 ∙ Uniprot:O95947 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant spondylocostal dysostosis (Supportive), mode of inheritance: AD
• spondylocostal dysostosis 5 (Moderate), mode of inheritance: Semidominant
• congenital anomaly of kidney and urinary tract (Limited), mode of inheritance: AD
• spondylocostal dysostosis 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondylocostal dysostosis 5	AD/AR	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	Musculoskeletal	23335591; 25564734; 28054739; 31015262

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBX6 gene.

• Spondylocostal dysostosis 5 (9 variants)
• Scoliosis (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX6 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	50	6	60
missense	1	1	120	2	1	125
nonsense	3		2			5
start loss			1			1
frameshift	7	6	3	1		17
inframe indel	1					1
splice donor/acceptor (+/-2bp)		1	3			4
splice region			3	4	2	9
non coding			2	14	5	21
Total	12	8	135	67	12

Highest pathogenic variant AF is 0.0000134

Variants in TBX6

This is a list of pathogenic ClinVar variants found in the TBX6 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-30086225-T-A		Spondylocostal dysostosis 5 • Spondylocostal dysostosis 2, autosomal recessive	Pathogenic (Apr 15, 2013)
16-30086227-A-G		Spondylocostal dysostosis 5	Likely pathogenic (-)
16-30086232-A-G			Uncertain significance (Jun 07, 2024)
16-30086235-G-C			Uncertain significance (Jun 29, 2020)
16-30086236-G-A		Scoliosis	Uncertain significance (Aug 01, 2019)
16-30086239-T-G			Uncertain significance (Aug 10, 2023)
16-30086245-C-T			Uncertain significance (Nov 11, 2024)
16-30086248-C-T		not specified	Uncertain significance (Jul 30, 2024)
16-30086258-G-A		Spondylocostal dysostosis 5	Uncertain significance (Jul 10, 2019)
16-30086258-G-T			Likely benign (May 05, 2023)
16-30086259-C-A		Spondylocostal dysostosis 5	Uncertain significance (Jul 10, 2019)
16-30086260-C-T			Uncertain significance (May 20, 2022)
16-30086267-C-T			Likely benign (Dec 31, 2019)
16-30086268-G-A		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
16-30086285-GA-TT			Uncertain significance (Oct 06, 2023)
16-30086285-G-GA		Spondylocostal dysostosis 5	Pathogenic (Nov 15, 2015)
16-30086292-C-A			Uncertain significance (Dec 10, 2022)
16-30086293-C-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
16-30086309-C-G			Likely benign (Oct 17, 2023)
16-30086309-C-T		not specified	Benign (Jan 31, 2024)
16-30086310-G-A			Uncertain significance (Jan 25, 2024)
16-30086324-C-T			Likely benign (Sep 11, 2023)
16-30086325-G-A			Uncertain significance (Aug 09, 2023)
16-30086327-C-T			Likely benign (Mar 29, 2022)
16-30086328-G-A		Inborn genetic diseases	Uncertain significance (Oct 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBX6	protein_coding	protein_coding	ENST00000395224	8	6095

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00681	0.990	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.535	254	279	0.910	0.0000186	2745
Missense in Polyphen		87	122.59	0.70967		1208
Synonymous	0.165	113	115	0.980	0.00000764	955
Loss of Function	2.57	7	19.1	0.366	0.00000115	192

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000237	0.000237
Ashkenazi Jewish	0.00169	0.00169
East Asian	0.000167	0.000163
Finnish	0.000694	0.000693
European (Non-Finnish)	0.000135	0.000123
Middle Eastern	0.000167	0.000163
South Asian	0.000164	0.000163
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: T-box transcription factor that plays an essential role in the determination of the fate of axial stem cells: neural vs mesodermal. Acts in part by down-regulating, a specific enhancer (N1) of SOX2, to inhibit neural development. Seems to play also an essential role in left/right axis determination and acts through effects on Notch signaling around the node as well as through an effect on the morphology and motility of the nodal cilia (By similarity). {ECO:0000250}.
• Disease: DISEASE: Spondylocostal dysostosis 5 (SCDO5) [MIM:122600]: A rare condition of variable severity characterized by vertebral and costal anomalies. The main feature include dwarfism, vertebral fusion, hemivertebrae, posterior rib fusion, reduced rib number, and other rib malformations. SCDO5 inheritance can be autosomal dominant or recessive. {ECO:0000269|PubMed:23335591, ECO:0000269|PubMed:25564734}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neural Crest Differentiation;Gene regulatory network modelling somitogenesis;Mesodermal Commitment Pathway (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.220
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.22

Haploinsufficiency Scores

• pHI: 0.169
• hipred: N
• hipred_score: 0.372
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.381

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbx6
• 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; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; embryo 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); reproductive system phenotype; 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); cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: tbx6
• Affected structure: CaP motoneuron
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;mesoderm formation;cell fate specification;mesoderm development;anatomical structure morphogenesis;negative regulation of neuron projection development;negative regulation of neuron maturation;signal transduction involved in regulation of gene expression;somite rostral/caudal axis specification;negative regulation of DNA-binding transcription factor activity;positive regulation of transcription by RNA polymerase II
• Cellular component: nuclear chromatin
• Molecular function: 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;protein binding