TBX6 (T-box transcription factor 6)

Gene

• Entrez ID: 6911
• Gene name: T-box transcription factor 6
• Gene symbol: TBX6
• Synonyms (NCBI Gene): SCDO5
• Chromosome: 16
• Chromosome location: 16p11.2
• Summary: This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2289292	C>G,T	Benign, pathogenic	Downstream transcript variant, synonymous variant, genic downstream transcript variant, coding sequence variant
rs3809624	T>A,C	Pathogenic	5 prime UTR variant, non coding transcript variant, intron variant
rs148435229	G>A,C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, synonymous variant
rs149724027	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, synonymous variant
rs200175825	C>T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs201620629	G>A,C	Pathogenic	Non coding transcript variant, stop gained, missense variant, coding sequence variant
rs202193096	G>A	Likely-pathogenic, pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs369603655	G>T	Conflicting-interpretations-of-pathogenicity	Intron variant
rs587777113	T>A	Pathogenic	Terminator codon variant, stop lost, downstream transcript variant, genic downstream transcript variant
rs756921502	C>G,T	Likely-pathogenic	Genic downstream transcript variant, missense variant, downstream transcript variant, coding sequence variant
rs758051786	C>-,CC	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs759383268	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, synonymous variant
rs786204039	->A	Pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant, downstream transcript variant
rs786204040	->G	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs879253776	->G	Pathogenic	Downstream transcript variant, frameshift variant, genic downstream transcript variant, coding sequence variant
rs879253857	CT>-	Pathogenic	Downstream transcript variant, frameshift variant, genic downstream transcript variant, coding sequence variant
rs1567342899	->C	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1596852902	->CCC	Pathogenic	Inframe insertion, non coding transcript variant, coding sequence variant
rs1596853067	C>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1596853085	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT734804	hsa-miR-874-5p	RNA-seq	31540331
MIRT1415316	hsa-miR-1225-3p	CLIP-seq
MIRT1415317	hsa-miR-1233	CLIP-seq
MIRT1415318	hsa-miR-147	CLIP-seq
MIRT1415319	hsa-miR-3151	CLIP-seq
MIRT1415320	hsa-miR-3184	CLIP-seq
MIRT1415321	hsa-miR-3689d	CLIP-seq
MIRT1415322	hsa-miR-3911	CLIP-seq
MIRT1415323	hsa-miR-423-5p	CLIP-seq
MIRT1415324	hsa-miR-4283	CLIP-seq
MIRT1415325	hsa-miR-4447	CLIP-seq
MIRT1415326	hsa-miR-4450	CLIP-seq
MIRT1415327	hsa-miR-4472	CLIP-seq
MIRT1415328	hsa-miR-4651	CLIP-seq
MIRT1415329	hsa-miR-4710	CLIP-seq
MIRT1415330	hsa-miR-491-5p	CLIP-seq
MIRT1415331	hsa-miR-608	CLIP-seq
MIRT1415332	hsa-miR-644	CLIP-seq
MIRT1415318	hsa-miR-147	CLIP-seq
MIRT2124630	hsa-miR-199a-5p	CLIP-seq
MIRT2124631	hsa-miR-199b-5p	CLIP-seq
MIRT1415319	hsa-miR-3151	CLIP-seq
MIRT1415320	hsa-miR-3184	CLIP-seq
MIRT1415321	hsa-miR-3689d	CLIP-seq
MIRT1415322	hsa-miR-3911	CLIP-seq
MIRT1415323	hsa-miR-423-5p	CLIP-seq
MIRT1415324	hsa-miR-4283	CLIP-seq
MIRT2124632	hsa-miR-4302	CLIP-seq
MIRT1415325	hsa-miR-4447	CLIP-seq
MIRT1415326	hsa-miR-4450	CLIP-seq
MIRT1415327	hsa-miR-4472	CLIP-seq
MIRT1415328	hsa-miR-4651	CLIP-seq
MIRT1415329	hsa-miR-4710	CLIP-seq
MIRT1415330	hsa-miR-491-5p	CLIP-seq
MIRT1415331	hsa-miR-608	CLIP-seq
MIRT1415332	hsa-miR-644	CLIP-seq
MIRT2346894	hsa-miR-1275	CLIP-seq
MIRT1415318	hsa-miR-147	CLIP-seq
MIRT2124630	hsa-miR-199a-5p	CLIP-seq
MIRT2124631	hsa-miR-199b-5p	CLIP-seq
MIRT1415319	hsa-miR-3151	CLIP-seq
MIRT1415322	hsa-miR-3911	CLIP-seq
MIRT2124632	hsa-miR-4302	CLIP-seq
MIRT1415325	hsa-miR-4447	CLIP-seq
MIRT1415327	hsa-miR-4472	CLIP-seq
MIRT2346895	hsa-miR-4525	CLIP-seq
MIRT2346896	hsa-miR-4665-5p	CLIP-seq
MIRT2346897	hsa-miR-4723-5p	CLIP-seq
MIRT1415330	hsa-miR-491-5p	CLIP-seq
MIRT2346898	hsa-miR-625	CLIP-seq
MIRT1415332	hsa-miR-644	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS
GO:0000785	Component	Chromatin	IBA
GO:0000785	Component	Chromatin	IEA
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001707	Process	Mesoderm formation	IEA
GO:0001708	Process	Cell fate specification	IBA
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	9933572
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003714	Function	Transcription corepressor activity	IEA
GO:0003714	Function	Transcription corepressor activity	ISS
GO:0005515	Function	Protein binding	IPI	24722188, 25416956, 32296183, 32814053
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007498	Process	Mesoderm development	IEA
GO:0007498	Process	Mesoderm development	TAS	9933572
GO:0007501	Process	Mesodermal cell fate specification	IEA
GO:0009653	Process	Anatomical structure morphogenesis	IEA
GO:0009653	Process	Anatomical structure morphogenesis	TAS	9888994
GO:0010977	Process	Negative regulation of neuron projection development	IEA
GO:0014043	Process	Negative regulation of neuron maturation	IEA
GO:0023019	Process	Signal transduction involved in regulation of gene expression	IEA
GO:0032525	Process	Somite rostral/caudal axis specification	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0061629	Function	RNA polymerase II-specific DNA-binding transcription factor binding	IEA
GO:0061629	Function	RNA polymerase II-specific DNA-binding transcription factor binding	ISS
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IEA

Other IDs

• MIM: 602427
• HGNC: 11605
• e!Ensembl: ENSG00000149922

Protein

• UniProt ID: O95947
• Protein name: T-box transcription factor TBX6 (T-box protein 6)
• Protein 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 a
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00907	T-box	93 → 273	T-box	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in fetal tail bud, posterior spinal tissue, intervertebral disk and testis. Also expressed in adult testis, kidney, lung, muscle and thymus.
• Sequence:

  MYHPRELYPSLGAGYRLGPAQPGADSSFPPALAEGYRYPELDTPKLDCFLSGMEAAPRTL
  AAHPPLPLLPPAMGTEPAPSAPEALHSLPGVSLSLENRELWKEFSSVGTEMIITKAGRRM
  FPACRVSVTGLDPEARYLFLLDVIPVDGARYRWQGRRWEPSGKAEPRLPDRVYIHPDSPA
  TGAHWMRQPVSFHRVKLTNSTLDPHGHLILHSMHKYQPRIHLVRAAQLCSQHWGGMASFR
  FPETTFISVTAYQNPQITQLKIAANPFAKGFRENGRNCKRERDARVKRKLRGPEPAATEA
  YGSGDTPGGPCDSTLGGDIRESDPEQAPAPGEATAAPAPLCGGPSAEAYLLHPAAFHGAP
  SHLPTRSPSFPEAPDSGRSAPYSAAFLELPHGSGGSGYPAAPPAVPFAPHFLQGGPFPLP
  YTAPGGYLDVGSKPMY

• Sequence length: 436

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Scoliosis	Pathogenic; Likely pathogenic	rs1596852902, rs1596853067, rs1596853085	RCV000855738 RCV000855735 RCV000855746	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spondylocostal dysostosis 2, autosomal recessive	Pathogenic	rs587777113	RCV002269823	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spondylocostal dysostosis 5	Pathogenic; Likely pathogenic	rs587777113, rs2151031013, rs762321473, rs2072634304, rs786204039, rs786204040, rs879253776, rs758051786, rs879253857, rs2543659119, rs1567342899, rs369015359	RCV000087033 RCV001785053 RCV001783853 RCV002283684 RCV000167864 RCV000167865 RCV000235075 RCV000235054 RCV000235062 RCV003986016 RCV000735670 RCV001254941	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
TBX6-related disorder	Likely pathogenic	rs754292378, rs2072686903, rs2543660247	RCV003397275 RCV003400073 RCV003902089	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT SPONDYLOCOSTAL DYSOSTOSIS	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE SPONDYLOCOSTAL DYSOSTOSIS	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CAKUT	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ANOMALY OF KIDNEY AND URINARY TRACT	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JARCHO-LEVIN SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAYER-ROKITANSKY-KUSTER-HAUSER SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE SCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental abnormality	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS, UNSPECIFIED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Accessory rib	Accessory Rib	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia, Sickle Cell	Anemia	BEFREE	23335591, 27861764, 31015262		★☆☆☆☆ Found in Text Mining only
Atresia of vagina	Atresia Of Vagina	BEFREE	31233831		★☆☆☆☆ Found in Text Mining only
Atrioventricular Block	Atrioventricular block	BEFREE	30305954		★☆☆☆☆ Found in Text Mining only
Autosomal dominant spondylocostal dysostosis	Spondylocostal Dysostosis	BEFREE	23335591, 28054739		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal dominant spondylocostal dysostosis	Spondylocostal Dysostosis	ORPHANET_DG	23335591		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal dominant spondylocostal dysostosis	Spondylocostal Dysostosis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cakut	Congenital anomalies of kidney and urinary tract	BEFREE	30578417, 30604070		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cakut	Congenital anomalies of kidney and urinary tract	CTD_human_DG	30578417		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cakut	Congenital anomalies of the kidney and urinary tract	Pubtator	30578417	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Defect of vertebral segmentation	Abnormal spinal segmentation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
gaze palsy familial horizontal with progressive scoliosis	Horizontal gaze palsy with progressive scoliosis	Pubtator	32933559	Associate	★☆☆☆☆ Found in Text Mining only
Jarcho-Levin syndrome	Jarcho-Levin Syndrome	BEFREE	27861764, 28990171		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Jarcho-Levin syndrome	Jarcho-Levin Syndrome	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Diseases	Kidney disease	Pubtator	36161696	Associate	★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal carnitine transport defect	Renal Carnitine Transport Defect	BEFREE	23335591, 27861764, 31015262		★☆☆☆☆ Found in Text Mining only
Sacral defect and anterior sacral meningocele	Sacral defect	Pubtator	18466071	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis	Scoliosis	Pubtator	25564734, 30019117, 30196550, 30803986, 31827250, 32672867, 32815649, 32933559, 34440387, 36161696	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Scoliosis, unspecified	Scoliosis	CLINVAR_DG	25564734		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Scoliosis, unspecified	Scoliosis	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs ambiguus	Situs ambiguus	BEFREE	27637763, 28606934		★☆☆☆☆ Found in Text Mining only
Spina Bifida Occulta	Spina bifida occulta	HPO_DG			★☆☆☆☆ Found in Text Mining only
SPONDYLOCOSTAL DYSOSTOSIS 5	Spondylocostal Dysostosis	CLINVAR_DG	23335591, 25564734		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SPONDYLOCOSTAL DYSOSTOSIS 5	Spondylocostal Dysostosis	UNIPROT_DG	23335591, 25564734		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SPONDYLOCOSTAL DYSOSTOSIS 5	Spondylocostal Dysostosis	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SPONDYLOCOSTAL DYSOSTOSIS 5	Spondylocostal Dysostosis	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Spondylocostal dysostosis autosomal recessive	Spondylocostal dysostosis	Pubtator	18466071, 37984529	Associate	★☆☆☆☆ Found in Text Mining only