TBX21
T-box transcription factor 21, the group of T-box transcription factors
Basic information
Region (hg38): 17:47733236-47746122
Links
Phenotypes
GenCC
Source:
- immunodeficiency 88 (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 88 | AR | Allergy/Immunology/Infectious | Individuals have been described as having increased risk of mycobacterial infection, and awareness may allow preventative measures (eg, related to vaccinations) and early and aggressive treatment | Allergy/Immunology/Infectious | 33296702; 34160550 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX21 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 | 5 | |||||
| missense | 34 | 35 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 2 | 2 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 34 | 3 | 3 |
Variants in TBX21
This is a list of pathogenic ClinVar variants found in the TBX21 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-47733537-G-A | Asthma, nasal polyps, and aspirin intolerance • Asthma, nasal polyps, and aspirin intolerance;Immunodeficiency 88 | Uncertain significance (Mar 30, 2021) | ||
| 17-47733544-C-A | not specified | Uncertain significance (Nov 15, 2021) | ||
| 17-47733553-C-G | not specified | Benign (Jan 24, 2024) | ||
| 17-47733566-C-T | not specified | Uncertain significance (Sep 26, 2023) | ||
| 17-47733567-C-A | Immunodeficiency 88;Asthma, nasal polyps, and aspirin intolerance • not specified | Uncertain significance (Jun 07, 2024) | ||
| 17-47733588-C-A | not specified | Uncertain significance (Apr 25, 2022) | ||
| 17-47733629-C-T | not specified | Uncertain significance (Dec 14, 2021) | ||
| 17-47733644-G-A | not specified | Uncertain significance (May 10, 2022) | ||
| 17-47733672-G-C | not specified | Uncertain significance (Oct 05, 2022) | ||
| 17-47733695-C-T | not specified | Uncertain significance (Feb 28, 2024) | ||
| 17-47733696-C-T | not specified | Uncertain significance (May 23, 2024) | ||
| 17-47733705-C-T | not specified | Uncertain significance (Feb 14, 2023) | ||
| 17-47733746-G-T | not specified | Uncertain significance (Nov 09, 2023) | ||
| 17-47733756-G-T | not specified | Uncertain significance (Oct 27, 2022) | ||
| 17-47733765-C-T | not specified | Uncertain significance (Jan 23, 2024) | ||
| 17-47733780-C-G | Asthma, nasal polyps, and aspirin intolerance • Asthma, nasal polyps, and aspirin intolerance;Immunodeficiency 88 | Uncertain significance (Mar 30, 2021) | ||
| 17-47733786-C-T | not specified | Uncertain significance (Nov 10, 2022) | ||
| 17-47733812-G-A | not specified | Uncertain significance (Oct 12, 2021) | ||
| 17-47733844-A-G | Immunodeficiency 88 • not specified | Benign (Jan 24, 2024) | ||
| 17-47733862-A-G | TBX21-related disorder | Likely benign (Jun 25, 2019) | ||
| 17-47733886-C-A | not specified | Uncertain significance (Jun 06, 2023) | ||
| 17-47733920-GAGATG-AGTTTA | Immunodeficiency 88 | Pathogenic (Nov 29, 2021) | ||
| 17-47742731-G-A | not specified | Uncertain significance (May 18, 2023) | ||
| 17-47743174-G-A | Likely benign (Dec 31, 2019) | |||
| 17-47744192-C-T | Likely benign (May 31, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TBX21 | protein_coding | protein_coding | ENST00000177694 | 6 | 12876 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.996 | 0.00364 | 125745 | 0 | 3 | 125748 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 222 | 289 | 0.769 | 0.0000164 | 3440 |
| Missense in Polyphen | 78 | 127 | 0.61417 | 1479 | ||
| Synonymous | 0.784 | 106 | 117 | 0.908 | 0.00000670 | 1093 |
| Loss of Function | 4.04 | 1 | 21.0 | 0.0477 | 0.00000109 | 231 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000545 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.0000545 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs (PubMed:10761931). Activates transcription of a set of genes important for Th1 cell function, including those encoding IFN-gamma and the chemokine receptor CXCR3. Activates IFNG and CXCR3 genes in part by recruiting chromatin remodeling complexes including KDM6B, a SMARCA4- containing SWI/SNF-complex, and an H3K4me2-methyltransferase complex to their promoters and all of these complexes serve to establish a more permissive chromatin state conducive with transcriptional activation (By similarity). Can activate Th1 genes also via recruitment of Mediator complex and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1) in the form of the super elongation complex (SEC) to super-enhancers and associated genes in activated Th1 cells (PubMed:27292648). Inhibits the Th17 cell lineage commitment by blocking RUNX1-mediated transactivation of Th17 cell-specific transcriptinal regulator RORC. Inhibits the Th2 cell lineage commitment by suppressing the production of Th2 cytokines, such as IL-4, IL-5, and IL- 13, via repression of transcriptional regulators GATA3 and NFATC2. Protects Th1 cells from amplifying aberrant type-I IFN response in an IFN-gamma abundant microenvironment by acting as a repressor of type-I IFN transcription factors and type-I IFN-stimulated genes. Acts as a regulator of antiviral B-cell responses; controls chronic viral infection by promoting the antiviral antibody IgG2a isotype switching and via regulation of a broad antiviral gene expression program (By similarity). {ECO:0000250|UniProtKB:Q9JKD8, ECO:0000269|PubMed:10761931, ECO:0000269|PubMed:27292648}.;
- Disease
- DISEASE: Asthma, with nasal polyps and aspirin intolerance (ANPAI) [MIM:208550]: A condition consisting of asthma, aspirin sensitivity and nasal polyposis. Nasal polyposis is due to chronic inflammation of the paranasal sinus mucosa, leading to protrusion of edematous polyps into the nasal cavities. {ECO:0000269|PubMed:15806396}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Inflammatory bowel disease (IBD) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Endoderm Differentiation;Development and heterogeneity of the ILC family;IL12 signaling mediated by STAT4;Glucocorticoid receptor regulatory network;IL27-mediated signaling events;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;IL12-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.552
Intolerance Scores
- loftool
- 0.0673
- rvis_EVS
- -0.74
- rvis_percentile_EVS
- 13.94
Haploinsufficiency Scores
- pHI
- 0.276
- hipred
- Y
- hipred_score
- 0.789
- ghis
- 0.514
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.803
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tbx21
- Phenotype
- respiratory system phenotype; hematopoietic 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); neoplasm; 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); immune system phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;multicellular organism development;response to virus;T cell differentiation;negative regulation of interleukin-2 production;proteasome-mediated ubiquitin-dependent protein catabolic process;regulation of T cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of isotype switching to IgG isotypes;cellular response to organic substance;lymphocyte migration;negative regulation of T-helper 17 cell differentiation;negative regulation of T-helper 17 cell lineage commitment;negative regulation of T-helper 2 cell cytokine production
- Cellular component
- nucleus;neuronal cell body
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding;transcription regulatory region DNA binding