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TEC, a cytoplasmic protein-tyrosine kinase involved in T cell receptor signalling, has emerged as a candidate gene in rheumatoid arthritis. Evidence from familial studies and large-scale pharmacogenomics meta-analyses suggests that rare, potentially pathogenic variants affecting T cell activation pathways may contribute to disease risk (PMID:31848144, PMID:28607508).
The overall clinical validity of the TEC–rheumatoid arthritis association is considered Limited. In one study, the clustering of immune-related gene variants across 14 families raised the possibility of a role for TEC in autoimmunity, although the number of probands with clearly segregating TEC variants remains low (PMID:31848144). Similarly, meta‑analytical findings have implicated TEC among several genes associated with anti‑TNF treatment response, but without definitive causal variants being established (PMID:28607508).
Genetic evidence for TEC is limited by the absence of individually reported, pathogenic HGVS‐described variants. While candidate gene approaches in familial autoimmunity studies have identified rare variants within T cell receptor signalling complexes, TEC-specific alterations have not yet met stringent criteria for causation. This results in a lower ClinGen genetic evidence score (PMID:31848144).
Functional studies, however, provide moderately strong support for a biological role of TEC in immune regulation. Promoter assays in murine models showed that transcription factors such as PU.1 and Sp1 are critical for TEC expression (PMID:9177279). In addition, research into chimeric oncoprotein products involving TEC demonstrated that its activity can be modulated by interactions with GAPDH, further reinforcing a mechanistically plausible link to cellular processes relevant to autoimmunity (PMID:17302560).
When integrating the genetic and experimental findings, a coherent narrative emerges: while direct genetic evidence for TEC‐mediated risk in rheumatoid arthritis is currently limited, the functional data strongly indicate that perturbations in TEC regulation can alter T cell signalling. This suggests that TEC is a promising candidate, albeit one for which further evidence is needed to support its modern clinical utility.
Key take‑home: TEC represents a promising candidate gene in rheumatoid arthritis due to its central role in T cell receptor signaling; however, additional genetic evidence is required to fully support its utility in diagnostic decision‑making and therapeutic intervention.
Gene–Disease AssociationLimitedLimited familial evidence with candidate clustering in 14 families (PMID:31848144) and pharmacogenomic meta‑analysis support (PMID:28607508), but definitive TEC‑specific pathogenic variants have not been established. Genetic EvidenceLimitedCandidate gene inclusion in T cell receptor signalling clusters is noted, yet the absence of a definitive, HGVS‑reported TEC variant limits the genetic evidence. Functional EvidenceModerateFunctional assays demonstrating TEC promoter regulation by PU.1 and Sp1 (PMID:9177279) and modulation via GAPDH interactions (PMID:17302560) provide moderate support for TEC’s involvement in immune regulation. |