TRAC

T cell receptor alpha constant, the group of T cell receptor alpha locus at 14q11.2

Basic information

Region (hg38): 14:22547505-22552156

Links

ENSG00000277734 ∙ NCBI:28755 ∙ OMIM:186880 ∙ HGNC:12029 ∙ Uniprot:P01848 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• TCR-alpha-beta-positive T-cell deficiency (Supportive), mode of inheritance: AR
• TCR-alpha-beta-positive T-cell deficiency (Limited), mode of inheritance: Unknown
• TCR-alpha-beta-positive T-cell deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 7	AR	Allergy/Immunology/Infectious	Prophylactic measures, surveillance, and early and aggressive treatment of infections may be beneficial; BMT has been described	Allergy/Immunology/Infectious	21206088

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAC gene.

• TCR-alpha-beta-positive T-cell deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAC 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						0
missense						0
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding						0
Total	1	0	0	0	0

Variants in TRAC

This is a list of pathogenic ClinVar variants found in the TRAC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-22550664-G-A		TCR-alpha-beta-positive T-cell deficiency	Pathogenic (Feb 01, 2011)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constant region of T cell receptor (TR) alpha chain (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation (PubMed:23524462). The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post- thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity (PubMed:15040585). {ECO:0000303|PubMed:15040585, ECO:0000303|PubMed:23524462, ECO:0000303|PubMed:24600447, ECO:0000303|PubMed:25493333}.
• Disease: DISEASE: Immunodeficiency 7 (IMD7) [MIM:615387]: A primary immunodeficiency disorder manifesting with recurrent respiratory infections, candidiasis, diarrhea, and failure to thrive. Patients show a clear predisposition to herpes viral infections, and features of immune dysregulation, including hypereosinophilia, vitiligo, and alopecia areata. Other features include lymphadenopathy and hepatosplenomegaly. CD3+ T-cells express TCR- gamma/delta, but little or no TCR-alpha/beta. {ECO:0000269|PubMed:21206088}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Phosphorylation of CD3 and TCR zeta chains;Generation of second messenger molecules;Translocation of ZAP-70 to Immunological synapse;Downstream TCR signaling;TCR signaling;PD-1 signaling;Costimulation by the CD28 family;CD4 T cell receptor signaling-ERK cascade;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Gene ontology

• Biological process: adaptive immune response;regulation of immune response;T cell receptor signaling pathway
• Cellular component: plasma membrane;integral component of membrane