TRAC
otherT cell receptor alpha constant, the group of T cell receptor alpha locus at 14q11.2
Gene summary
T cell receptors recognize foreign antigens which have been processed as small peptides and bound to major histocompatibility complex (MHC) molecules at the surface of antigen presenting cells (APC). Each T cell receptor is a dimer consisting of one alpha and one beta chain or one delta and one gamma chain. In a single cell, the T cell receptor loci are rearranged and expressed in the order delta, gamma, beta, and alpha. If both delta and gamma rearrangements produce functional chains, the cell expresses delta and gamma. If not, the cell proceeds to rearrange the beta and alpha loci. This region represents the germline organization of the T cell receptor alpha and delta loci. Both the alpha and delta loci include V (variable), J (joining), and C (constant) segments and the delta locus also includes diversity (D) segments. The delta locus is situated within the alpha locus, between the alpha V and J segments. During T cell development, the delta chain is synthesized by a recombination event at the DNA level joining a D segment with a J segment; a V segment is then joined to the D-J gene. The alpha chain is synthesized by recombination joining a single V segment with a J segment. For both chains, the C segment is later joined by splicing at the RNA level. Recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random additional of nucleotides by terminal deoxynucleotidyltransferase. Five variable segments can be used in either alpha or delta chains and are described by TRAV/DV symbols. Several V and J segments of the alpha locus are known to be incapable of encoding a protein and are considered pseudogenes. [provided by RefSeq, Aug 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014160
Submitter: ClinGen
*TRAC* was first reported in relation to autosomal recessive TCR-alpha-beta-positive T-cell deficiency in 2011 (Morgan NV, et al., 2011, PMID: 21206088 ). The *TRAC* gene encodes for the constant region of the TCR subunit and is essential for membrane expression of the αβTCR heterodimer, which recognizes a complex consisting of an antigen-derived peptide bound to a class I or class II MHC protein. *TRAC* deficiency is characterized by onset of recurrent bacterial and viral infections in infancy or early childhood. Evidence supporting the gene-disease relationship includes 3 probands plus 2 additional affected family members, all with the same homozygous c. *1G > A variant, reported in 2 publications (PMIDs: 21206088, 33909184). An additional patient, with homozygous Ser116Ter, was reported in doi.org/10.14785/lymphosign-2022-0001 (Garkaby et al., 2022). Heterozygous parents were reported to be clinically unaffected in all families. This gene-disease relationship is also supported by experimental evidence, including its function in the TCR (PMID: 2421164) which is altered in patient cells (PMID: 33909184). As well as expression that is enriched in lymphoid tissues and specifically enhanced in T-cells but altered in patient cells (PMID: 21206088). In summary, there is moderate evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was originally approved by the ClinGen SCID-CID GCEP on August 18, 2022. This genedisease relationship was re-evaluated on July 17, 2025. As a result of this re-evaluation, no new evidence was indentified and the classification did not change.
Inheritance Pattern: AR
Disease ID:MONDO:0014160
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014160
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0014160
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: Prophylactic measures, surveillance, and early and aggressive treatment of infections may be beneficial; BMT has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRAC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 0 | 0 | 0 | 0 | 1 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000480116.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Phosphorylation of CD3 and TCR zeta chains
- Generation of second messenger molecules
- Translocation of ZAP-70 to Immunological synapse
- Downstream TCR signaling
- TCR signaling
Biological Process
- adaptive immune response
- regulation of immune response
- T cell receptor signaling pathway
Cellular Component
- plasma membrane
- integral component of membrane
dbNSFP Gene Annotations
Source:
- 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.;