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PALS1 – COVID‑19

The current evidence supporting the association between PALS1 (HGNC:18669) and COVID‑19 (MONDO:0100096) is limited. Although PALS1 was identified as one of several human proteins that interact with SARS‑CoV‑2 in large‐scale interactome studies (PMID:34530086), there are no reports of PALS1 variants segregating with COVID‑19 severity, and no unrelated probands or familial segregation data have been documented. In multi‑patient studies, PALS1 was nominated as a candidate gene potentially modulating viral entry and pathogenesis, yet the genetic evidence remains nominal without direct coding changes or recurrent rare variants. The lack of robust case‑control data and segregation analysis confines the overall curative validity to a limited level.

Functional studies, however, lend some biological plausibility to the proposed association. Structural assessments have demonstrated that the PDZ domain of PALS1 can interact with the envelope proteins of SARS‑CoV‑2, suggesting a mechanism in which altered tight junction integrity might contribute to viral dissemination or altered host responses (PMID:33758649). In addition, bioinformatics analyses from subsequent studies have reinforced these findings by proposing that modulation of host‑cell protein interactions could impact COVID‑19 susceptibility (PMID:38902252). These converging lines of functional evidence are intriguing but require further genetic and clinical validation to support diagnostic decision‑making and therapeutic strategies.

References

  • Gene • 2022 • An overview of human proteins and genes involved in SARS‑CoV‑2 infection PMID:34530086
  • Scientific reports • 2024 • Predicting human and viral protein variants affecting COVID‑19 susceptibility and repurposing therapeutics PMID:38902252
  • Computational and structural biotechnology journal • 2021 • Structural determinants driving the binding process between PDZ domain of wild type human PALS1 protein and SLiM sequences of SARS‑CoV E proteins PMID:33758649

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Association is based on non‐segregation, candidate interactome studies and bioinformatic nomination without direct proband evidence (PMID:34530086) (PMID:38902252).

Genetic Evidence

Limited

No specific PALS1 variants have been reported in COVID‑19 cases, and there is a lack of familial or case‑control data to support a genetic association.

Functional Evidence

Moderate

Experimental data demonstrate that the PALS1 PDZ domain interacts with SARS‑CoV‑2 envelope proteins, supporting a plausible mechanistic role in modulating viral infection and host cell junction integrity (PMID:33758649).