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.
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