TBX22 (T-box transcription factor 22)

Gene

• Entrez ID: 50945
• Gene name: T-box transcription factor 22
• Gene symbol: TBX22
• Synonyms (NCBI Gene): ABERS, CLPA, CPX, TBXX, dJ795G23.1
• Chromosome: X
• Chromosome location: Xq21.1
• 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. Mutations in this gene have been assoc

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28935177	A>T	Pathogenic	Coding sequence variant, missense variant
rs104894943	C>T	Pathogenic	Coding sequence variant, missense variant
rs104894944	G>T	Pathogenic	Coding sequence variant, 5 prime UTR variant, missense variant
rs104894945	G>C,T	Pathogenic	Stop gained, missense variant, upstream transcript variant, coding sequence variant, 5 prime UTR variant, genic upstream transcript variant
rs104894946	T>C	Pathogenic	Coding sequence variant, missense variant
rs200060292	T>A	Likely-pathogenic, pathogenic	Intron variant
rs1555993323	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1602410858	->GCT	Pathogenic	Coding sequence variant, inframe insertion
rs1602410916	G>A	Pathogenic	Splice donor variant
rs1602411954	G>C	Pathogenic	Splice donor variant
rs1602414282	G>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018409	hsa-miR-335-5p	Microarray	18185580
MIRT022915	hsa-miR-124-3p	Microarray	18668037
MIRT1415147	hsa-miR-1303	CLIP-seq
MIRT1415148	hsa-miR-340	CLIP-seq
MIRT1415149	hsa-miR-3659	CLIP-seq
MIRT1415150	hsa-miR-433	CLIP-seq
MIRT1415151	hsa-miR-4528	CLIP-seq
MIRT1415152	hsa-miR-4464	CLIP-seq
MIRT1415153	hsa-miR-4748	CLIP-seq
MIRT1415154	hsa-miR-486-5p	CLIP-seq
MIRT1415155	hsa-miR-489	CLIP-seq
MIRT1415156	hsa-miR-514	CLIP-seq
MIRT1415157	hsa-miR-514b-3p	CLIP-seq
MIRT1415158	hsa-miR-579	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	17846996
GO:0000785	Component	Chromatin	IBA
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	17846996
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:0001708	Process	Cell fate specification	IBA
GO:0003677	Function	DNA binding	IDA	17846996
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	25416956, 32296183, 32814053
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	17846996
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:0045892	Process	Negative regulation of DNA-templated transcription	IDA	17846996
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IEA

Other IDs

• MIM: 300307
• HGNC: 11600
• e!Ensembl: ENSG00000122145

Protein

• UniProt ID: Q9Y458
• Protein name: T-box transcription factor TBX22 (T-box protein 22)
• Protein function: Probable transcriptional regulator involved in developmental processes. This is major determinant crucial to palatogenesis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00907	T-box	94 → 283	T-box	Domain

• Tissue specificity: TISSUE SPECIFICITY: Seems to be expressed at a low level.
• Sequence:

  MALSSRARAFSVEALVGRPSKRKLQDPIQAEQPELREKKGGEEEEERRSSAAGKSEPLEK
  QPKTEPSTSASSGCGSDSGYGNSSESLEEKDIQMELQGSELWKRFHDIGTEMIITKAGRR
  MFPSVRVKVKGLDPGKQYHVAIDVVPVDSKRYRYVYHSSQWMVAGNTDHLCIIPRFYVHP
  DSPCSGETWMRQIISFDRMKLTNNEMDDKGHIILQSMHKYKPRVHVIEQGSSVDLSQIQS
  LPTEGVKTFSFKETEFTTVTAYQNQQITKLKIERNPFAKGFRDTGRNRGVLDGLLETYPW
  RPSFTLDFKTFGADTQSGSSGSSPVTSSGGAPSPLNSLLSPLCFSPMFHLPTSSLGMPCP
  EAYLPNVNLPLCYKICPTNFWQQQPLVLPAPERLASSNSSQSLAPLMMEVPMLSSLGVTN
  SKSGSSEDSSDQYLQAPNSTNQMLYGLQSPGNIFLPNSITPEALSCSFHPSYDFYRYNFS
  MPSRLISGSNHLKVNDDSQVSFGEGKCNHVHWYPAINHYL

• Sequence length: 520

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
Cleft palate with ankyloglossia	Pathogenic; Likely pathogenic	rs1602411954, rs104894943, rs104894944, rs1602410916, rs2519860231, rs104894945, rs104894946, rs1602410858, rs28935177	RCV000012081 RCV000012082 RCV000012083 RCV000012084 RCV000012085 RCV000012086 RCV000012087 RCV000012088 RCV000012089	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Cleft palate with or without ankyloglossia, X-linked	Likely pathogenic; Pathogenic	rs104894945, rs1602414282, rs2519860240	RCV006249555 RCV000012090 RCV003990503	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Abruzzo-Erickson syndrome	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar CTD	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Cleft palate	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CLEFT PALATE X-LINKED	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLEFT PALATE, X-LINKED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mendelian syndromes with cleft lip/palate	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Orofacial cleft	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OROFACIAL CLEFTING SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TBX22-related disorder	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
URANOSTAPHYLOSCHISIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED CLEFT PALATE AND ANKYLOGLOSSIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Abruzzo Erickson syndrome	Cleft palate with coloboma of eye and deafness	BEFREE	22784330		★☆☆☆☆ Found in Text Mining only
Abruzzo Erickson syndrome	Cleft palate with coloboma of eye and deafness	ORPHANET_DG	22784330		★☆☆☆☆ Found in Text Mining only
Abruzzo Erickson syndrome	Cleft palate with coloboma of eye and deafness	GENOMICS_ENGLAND_DG	22784330		★☆☆☆☆ Found in Text Mining only
Abruzzo Erickson syndrome	Cleft palate with coloboma of eye and deafness	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Abruzzo Erickson syndrome	Cleft palate with coloboma of eye and deafness	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Abruzzo-Erickson syndrome	Abruzzo-Erickson Syndrome	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Acute monocytic leukemia	Monocytic Leukemia	BEFREE	28013106, 29051180, 30119908, 30837643, 31173485, 31547736		★☆☆☆☆ Found in Text Mining only
Adult Acute Myeloblastic Leukemia	Myeloblastic Leukemia	BEFREE	30541745		★☆☆☆☆ Found in Text Mining only
Ankyloglossia	Ankyloglossia	BEFREE	12204278, 12374769, 17846996, 17868388, 19648124, 19648291, 21375406, 21905918, 22784330, 25373698, 29704302, 30462376		★☆☆☆☆ Found in Text Mining only
Ankyloglossia	Ankyloglossia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anodontia	Anodontia	Pubtator	21248356	Associate	★☆☆☆☆ Found in Text Mining only
Aortic Valve Stenosis	Aortic Valve Sclerosis	BEFREE	28552098		★☆☆☆☆ Found in Text Mining only
Atrial Septal Defects	Atrial Septal Defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood Acute Myeloid Leukemia	Acute Myeloid Leukemia	BEFREE	30541745		★☆☆☆☆ Found in Text Mining only
Cleft Lip	Cleft lip	Pubtator	21248356, 28877219	Associate	★☆☆☆☆ Found in Text Mining only
Cleft Palate	Cleft palate	Pubtator	21248356, 26323392, 36901988	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Cleft Palate with Ankyloglossia	Cleft Palate With Ankyloglossia	BEFREE	11559848, 12374769, 12668595, 19418442, 22784330		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Cleft Palate with Ankyloglossia	Cleft Palate With Ankyloglossia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Clinodactyly	Clinodactyly	GENOMICS_ENGLAND_DG	22784330		★☆☆☆☆ Found in Text Mining only
Clinodactyly of fingers	Clinodactyly	GENOMICS_ENGLAND_DG	22784330		★☆☆☆☆ Found in Text Mining only
Coloboma of the Retina	Retinal coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	20126641	Associate	★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital coloboma of iris	Congenital Coloboma Of Iris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Coronal hypospadias	Coronal hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	BEFREE	10656877, 11591888, 12083969		★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic fibrosis	Pubtator	10656877	Inhibit	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysmorphism	Dysmorphism	BEFREE	25373698		★☆☆☆☆ Found in Text Mining only
Fundus coloboma	Fundus Coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gastrointestinal Neoplasms	Gastrointestinal Neoplasms	BEFREE	30630527		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	26323392	Associate	★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Hematologic Neoplasms	BEFREE	30566230		★☆☆☆☆ Found in Text Mining only
Hypodontia	Hypodontia	BEFREE	21248356		★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	26323392		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	20126641	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	28013106, 28286924, 28814164, 29051180, 29156201, 29167924, 29222237, 29264938, 29283906, 29296877, 29378418, 29532662, 29928134, 30113235, 30119908, 30423907, 30504411, 30541745, 30672340, 30837643, 31173485, 31203994, 31213803, 31547736		★☆☆☆☆ Found in Text Mining only
Macrotia	Macrotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcornea	Microcornea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Orofacial Cleft 1	Orofacial cleft	Pubtator	36901693	Associate	★☆☆☆☆ Found in Text Mining only
Osteomyelitis	Osteomyelitis	BEFREE	29484904		★☆☆☆☆ Found in Text Mining only
Otofaciocervical Syndrome	Otofaciocervical syndrome	Pubtator	36901693	Associate	★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	GENOMICS_ENGLAND_DG	22784330		★☆☆☆☆ Found in Text Mining only
Radioulnar Synostosis	Radioulnar Synostosis	GENOMICS_ENGLAND_DG	22784330		★☆☆☆☆ Found in Text Mining only
Radioulnar Synostosis	Radioulnar Synostosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	BEFREE	30566230		★☆☆☆☆ Found in Text Mining only
secondary acute myeloid leukemia	Myeloid leukemia	BEFREE	28030373, 29378418, 29908418, 29928134, 30024784, 30848394, 31173485, 31203994, 31760835		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Submucous cleft palate	Submucosal cleft palate	BEFREE	19648291, 22784330		★☆☆☆☆ Found in Text Mining only
Syndactyly of the toes	Syndactyly Of The Toes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Uranostaphyloschisis	Uranostaphyloschisis	BEFREE	12374769, 17868388, 19648124, 21375406, 22436304, 25373698, 26323392, 31596367		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Van der Woude syndrome	Van der woude syndrome	Pubtator	36901693	Associate	★☆☆☆☆ Found in Text Mining only
Van der Woude syndrome 2	Van der woude syndrome	Pubtator	36901693	Associate	★☆☆☆☆ Found in Text Mining only
Warburg Sjo Fledelius syndrome	Warburg micro syndrome	Pubtator	21248356	Associate	★☆☆☆☆ Found in Text Mining only
X-linked cleft palate and ankyloglossia	Cleft Palate And Ankyloglossia, X-Linked	BEFREE	11559848, 12204278, 19648124, 21248356		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-linked cleft palate and ankyloglossia	Cleft Palate And Ankyloglossia, X-Linked	ORPHANET_DG	11559848, 12374769, 14729838		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-linked cleft palate and ankyloglossia	Cleft Palate And Ankyloglossia, X-Linked	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations