PPP3CA
Overview
PPP3CA encodes the catalytic A-alpha subunit of calcineurin (protein phosphatase 2B), a calcium/calmodulin-dependent serine-threonine phosphatase that activates NFAT transcription factors. In the context of cancer genomics, PPP3CA was nominated as a novel significantly mutated gene in lung adenocarcinoma with missense mutations clustering in the autoinhibitory C-terminal domain, suggesting a gain-of-function mechanism.
Alterations observed in the corpus
- PPP3CA identified as a novel significantly mutated gene (SMG) in lung ADC in the 1,144-tumor NSCLC landscape study (660 lung ADC, 484 lung SqCC); missense mutations cluster in the autoinhibitory C-terminal domain, suggesting gain of function rather than loss of function. Co-occurs with activating KRAS mutations (p = 0.033). PMID:27158780
Cancer types (linked)
- LUAD: PPP3CA is a novel SMG in lung ADC; calcineurin pathway activation may cooperate with KRAS signaling (co-occurrence p = 0.033). PMID:27158780
Co-occurrence and mutual exclusivity
- Co-occurs with activating KRAS mutations (p = 0.033) in lung ADC, suggesting cooperative oncogenic signaling between calcineurin activation and the Ras pathway. PMID:27158780
Therapeutic relevance
- Calcineurin is the target of immunosuppressive drugs (cyclosporin, tacrolimus); gain-of-function mutations in PPP3CA could represent a vulnerability for calcineurin inhibition in lung ADC subsets co-mutated with KRAS, though no clinical data exist in the corpus.
Open questions
- Whether C-terminal autoinhibitory-domain mutations in PPP3CA are truly gain-of-function and whether calcineurin/NFAT activation cooperates with KRAS to drive lung ADC are not experimentally resolved.
Sources
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