Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
TESPA1 (HGNC:29109) has been implicated in rheumatoid arthritis (MONDO_0008383) based on recent familial whole‐exome sequencing studies that evaluated rare variants across immune‐related genes. In a study of 31 families with a history of autoimmune diseases—including rheumatoid arthritis—TESPA1 was identified among a cluster of T cell receptor signalling genes showing potential pathogenic contributions (PMID:31848144).
The genetic evidence emerged through heterozygous filtering and cosegregation analysis in these families. Notably, abnormal variants in key T cell activation pathway genes were found in 14 families with RA and related autoimmune phenotypes, suggesting an autosomal dominant pattern of inheritance (PMID:31848144).
Although no specific TESPA1 variant meeting full HGVS criteria was isolated in the report (for instance, an entry starting with a “c.” and containing a precise amino acid change), its inclusion in the candidate gene list supports its potential impact on disease risk. The absence of a detailed HGVS variant for TESPA1 limits the possibility to assess variant‐level segregation in affected individuals.
From a functional standpoint, while dedicated experimental studies on TESPA1 were not provided, its role in T cell receptor signalling is consistent with the known biology of rheumatoid arthritis. The broader evidence from pathway analyses and the involvement of related molecules in the LAT-SLP76 complex further bolster the biological plausibility of TESPA1 contributing to disease pathogenesis (PMID:31848144).
No significant conflicting evidence has been reported to dispute the association between TESPA1 and rheumatoid arthritis. However, additional studies are necessary to further confirm the segregation of TESPA1 variants and to elucidate their functional consequences within the immune system.
In summary, integration of genetic findings from familial autoimmunity studies and the supportive role of TESPA1 in T cell receptor signalling provides a limited yet promising association with rheumatoid arthritis. This evidence, while preliminary, is potentially valuable for diagnostic decision‑making and underscores the need for further investigation.
Gene–Disease AssociationLimitedTESPA1 was identified in a whole‐exome sequencing study of 31 families (31 families [PMID:31848144]) with rheumatoid arthritis signals in 14 families; however, the lack of specific, well‐segregated variant data limits definitive classification. Genetic EvidenceLimitedThe association is supported by detection of rare variants in a candidate gene screen within familial RA cases using heterozygous filtering, but without clear variant-level confirmation for TESPA1 (PMID:31848144). Functional EvidenceLimitedAlthough no direct functional assays for TESPA1 were reported, its known involvement in T cell receptor signalling lends biological plausibility to its role in disease, despite the current evidence being preliminary (PMID:31848144). |