TBX21

T-box transcription factor 21, the group of T-box transcription factors

Basic information

Region (hg38): 17:47733235-47746122

Links

ENSG00000073861 ∙ NCBI:30009 ∙ OMIM:604895 ∙ HGNC:11599 ∙ Uniprot:Q9UL17 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 88 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the TBX21 gene.

• Inborn genetic diseases (22 variants)
• Asthma, nasal polyps, and aspirin intolerance (5 variants)
• Asthma, nasal polyps, and aspirin intolerance;Immunodeficiency 88 (4 variants)
• not provided (3 variants)
• not specified (2 variants)
• Immunodeficiency 88;Asthma, nasal polyps, and aspirin intolerance (2 variants)
• Immunodeficiency 88 (1 variants)

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				1	2	3
missense			28		1	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	28	1	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		Asthma, nasal polyps, and aspirin intolerance;Immunodeficiency 88	Uncertain significance (Oct 05, 2022)
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)
17-47733705-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)
17-47744214-T-A		not specified	Uncertain significance (Sep 15, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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