DGKD – Systemic Lupus Erythematosus

DGKD, encoding diacylglycerol kinase delta, has been implicated in systemic lupus erythematosus (SLE) through familial exome sequencing analyses. In a multi‑patient study of 31 families with autoimmune disorders, DGKD was nominated as a candidate gene based on gene set enrichment and its involvement in T cell receptor signaling, with evidence of cosegregation observed in 14 families (PMID:31848144). Although no specific pathogenic variant in DGKD was reported, its inclusion among immune‑related genes highlights its potential role in familial SLE. This genetic evidence supports a limited association that merits further investigation for diagnostic and therapeutic considerations.

Complementary functional studies have demonstrated that DGKD undergoes alternative splicing to generate isoforms with distinct expression patterns and regulatory functions, underscoring its complex role in signal transduction (PMID:12200442). However, direct functional assays linking these isoforms to immune dysregulation in SLE remain sparse. The overall evidence, combining modest genetic signals with supportive but non–disease‑specific experimental data, currently assigns a limited strength to the DGKD‑SLE association. Key take‑home: DGKD represents a promising candidate for further research in SLE pathogenesis, although additional studies are required to confirm its clinical utility.

References

• Annals of the rheumatic diseases • 2020 • Germline genetic patterns underlying familial rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome highlight T cell-initiated autoimmunity PMID:31848144
• The Journal of biological chemistry • 2002 • Alternative splicing of the human diacylglycerol kinase delta gene generates two isoforms differing in their expression patterns and in regulatory functions PMID:12200442

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