TBX6 (T-box transcription factor 6)

Gene

• Entrez ID: 6911
• Gene name: T-box transcription factor 6
• Gene symbol: TBX6
• Synonyms (NCBI Gene): SCDO5
• Disease Acronyms (UniProt): 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	ISS
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001085	Function	RNA polymerase II transcription factor binding	ISS
GO:0001102	Function	RNA polymerase II activating transcription factor binding	ISS
GO:0001707	Process	Mesoderm formation	IEA
GO:0001708	Process	Cell fate specification	IBA	21873635
GO:0001947	Process	Heart looping	IBA	21873635
GO:0003205	Process	Cardiac chamber development	IBA	21873635
GO:0003677	Function	DNA binding	TAS	9933572
GO:0005515	Function	Protein binding	IPI	24722188, 25416956, 32296183, 32814053
GO:0005634	Component	Nucleus	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0007417	Process	Central nervous system development	IBA	21873635
GO:0007498	Process	Mesoderm development	TAS	9933572
GO:0008284	Process	Positive regulation of cell population proliferation	IBA	21873635
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:0043433	Process	Negative regulation of DNA-binding transcription factor activity	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

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

Causal
Disease term	Disease name	dbSNP ID	References
Congenital anomalies of kidney and urinary tract	Cakut	rs267606865, rs121908436, rs281875326, rs879255515, rs75462234, rs869320679, rs760905589, rs797045022, rs869320624, rs745597204, rs1114167358, rs1555879360, rs1577330805, rs1008555507	30578417
Macrocephaly	Macrocephaly	rs786204854, rs764333096, rs1557739557
Microcephaly	Microcephaly	rs397704721, rs267607176, rs267607177, rs397704725, rs267606717, rs267606718, rs199422202, rs121434311, rs199422203, rs199422126, rs387906274, rs121434305, rs199422125, rs199422135, rs189678019, rs199422184, rs137852994, rs137852995, rs137852996, rs137852997, rs145489194, rs80338860, rs137852494, rs121918609, rs199422207, rs199422206, rs29001566, rs864321658, rs199422138, rs199422139, rs199422141, rs199422144, rs199422147, rs199422151, rs199422152, rs199422153, rs199422157, rs199422159, rs199422160, rs199422161, rs140602858, rs199422164, rs199422165, rs148294838, rs199422134, rs199422168, rs199422172, rs199422173, rs199422131, rs199422177, rs199422180, rs199422185, rs199422186, rs199422187, rs143931757, rs199422189, rs199422192, rs199422194, rs199422195, rs199422196, rs199422197, rs199422199, rs753597039, rs1488084787, rs387906961, rs755862917, rs387907082, rs587776899, rs387907083, rs587776900, rs587776901, rs387907084, rs863223322, rs764201220, rs202247811, rs763915472, rs587776986, rs587777036, rs398122971, rs374351172, rs373278668, rs398122976, rs121909123, rs587783393, rs730882076, rs587783211, rs144716013, rs606231255, rs587783215, rs587783216, rs587783220, rs587783221, rs587783225, rs587783227, rs587783228, rs587783230, rs587783238, rs587783239, rs587783240, rs587783245, rs587783247, rs587783248, rs587783258, rs587783259, rs587783263, rs587783265, rs587783268, rs587783269, rs587783272, rs587783275, rs587783277, rs587783278, rs587783280, rs587783282, rs587783283, rs587783285, rs587783287, rs587783288, rs587783289, rs587783292, rs587783295, rs587784452, rs587783741, rs587783735, rs587783392, rs587783390, rs587783387, rs587783410, rs202058504, rs587783423, rs587783421, rs587783414, rs587784553, rs587784558, rs587784546, rs587784549, rs587784554, rs587784412, rs876661307, rs869025200, rs747831095, rs748529285, rs797045316, rs797045315, rs797045314, rs759632528, rs797045313, rs797045311, rs754282058, rs797045441, rs797045454, rs797045430, rs869312853, rs797046109, rs767399782, rs863225127, rs863225464, rs863225465, rs780270096, rs864321621, rs864321620, rs775277800, rs879253817, rs869312824, rs761447719, rs753406334, rs147622433, rs199422137, rs879255522, rs879255524, rs879255523, rs886037892, rs886037893, rs886037894, rs886037895, rs199422169, rs886041709, rs886041282, rs138228629, rs759188041, rs769688376, rs1057517688, rs1057519087, rs1057518268, rs933106143, rs201362977, rs754909135, rs1057520873, rs1060499758, rs1060499757, rs199422146, rs748016594, rs1085307120, rs763715733, rs1064795945, rs763800571, rs1554728351, rs1553227021, rs555866170, rs1553895368, rs1334947797, rs769818500, rs1321892596, rs1553227645, rs1404276011, rs1553228275, rs1554471681, rs1554496609, rs1555420891, rs1555418825, rs587784548, rs1555723585, rs199736219, rs745997770, rs765275884, rs1553924800, rs1554730137, rs1229568621, rs1482100822, rs979186313, rs758157294, rs1555294652, rs1555299107, rs1553264033, rs1553259539, rs1553254322, rs1553259528, rs981349334, rs1553264036, rs1553253022, rs754267846, rs776034810, rs1342429887, rs752140135, rs1006898944, rs571640983, rs1477524771, rs763909256, rs199910503, rs1553223496, rs759663956, rs1553446603, rs1555139372, rs1555143325, rs1350194762, rs1555141158, rs1553225179, rs769481947, rs769364943, rs748011724, rs1334301723, rs746341112, rs149225624, rs765113367, rs1567024512, rs142865061, rs772050241, rs201721894, rs1557966012, rs1379578836, rs1568334868, rs1185537869, rs1602333390, rs1163303148, rs774338373, rs770540184, rs1571600045, rs1571601267, rs1571602991, rs1588472215, rs1599841026, rs1558328287, rs1571600860, rs1571596976, rs1309880692, rs1435239428, rs1588634016, rs1751797979, rs1810830776, rs1815354949, rs1949984655, rs886039658, rs1943461045, rs777711720, rs2031759596, rs1555710223, rs1221031683, rs774069989, rs2058919680, rs1170413397, rs1213710245, rs1599851667, rs1599760058, rs1971033478, rs746967357
Scoliosis	Scoliosis, unspecified	rs1057518828, rs147296805, rs758163506, rs1555613564, rs1596852902, rs1596853067, rs1596853085	25564734
Spondylocostal dysostosis	SPONDYLOCOSTAL DYSOSTOSIS 5, Autosomal dominant spondylocostal dysostosis	rs113994158, rs71647808, rs71647806, rs118204035, rs786200899, rs786200900, rs777791545, rs786200902, rs104894675, rs786200903, rs104894676, rs104894024, rs113994160, rs387906978, rs387906979, rs118204034, rs398122970, rs587777113, rs201620629, rs786204039, rs786204040, rs786205519, rs879253776, rs758051786, rs879253857, rs771875570, rs1555439013, rs1555439118, rs912110093, rs762067626, rs1452984345, rs1555439061, rs538996447, rs1555439152, rs1206731716, rs1555439049, rs1555439063, rs1332109041, rs1447189148, rs1567342899, rs1211456697, rs1562551396, rs761454301, rs369015359	23335591, 25564734

Unknown
Disease term	Disease name	Evidence	References	Source
Spondylocostal Dysostosis	autosomal dominant spondylocostal dysostosis, spondylocostal dysostosis 5			GenCC
Multiple Sclerosis	Multiple Sclerosis			GWAS

Associations from Text Mining
Disease Name	Relationship Type	References
16p11.2 Deletion Syndrome	Associate	36161696
Cakut	Associate	30578417
Cervical Vertebral Dysplasia	Associate	18466071
gaze palsy familial horizontal with progressive scoliosis	Associate	32933559
Genitourinary Tract Anomalies	Associate	36161696
Jarcho Levin syndrome	Associate	36161696
Johnson Munson syndrome	Associate	32672867
Kidney Diseases	Associate	36161696
Klippel Feil Syndrome	Associate	18466071
Mullerian aplasia	Associate	23954021, 25813282, 33434492, 35361250, 36112137
Neoplasms	Inhibit	33174020
Ribbing disease	Associate	36161696
Sacral defect and anterior sacral meningocele	Associate	18466071
Scoliosis	Associate	25564734, 30019117, 30196550, 30803986, 31827250, 32672867, 32815649, 32933559, 34440387, 36161696
Spondylocostal dysostosis autosomal recessive	Associate	18466071, 37984529