PPP3CA protein phosphatase 3 catalytic subunit alpha
ENSG00000138814 · protein coding · Open Targets profile
Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser- 211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (By similarity). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (By similarity). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (By similarity). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (By similarity). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (By similarity). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (By similarity). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (By similarity). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). Required for antigen-specific T- cell proliferation response (By similarity). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (PubMed:30718414). Negatively regulates SLC9A1 activity (PubMed:31375679). {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63328, ECO:0000250|UniProtKB:P63329, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:17502104, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:23468591, ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827, ECO:0000269|PubMed:30254215, ECO:0000269|PubMed:30611118, ECO:0000269|PubMed:30718414, ECO:0000269|PubMed:31375679, ECO:0000269|PubMed:33691586}.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt loc med conf
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.21042999625205994 (upper bound 0.32896000146865845). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 8 registry trials, updated in the last three years, of the most advanced drugs against PPP3CA (voclosporin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Guangyan CaiChincse PLA General Hosptial · 1 of 1 trials Phase 2+
- James TumlinNephroNet, Inc. · 1 of 1 trials Phase 2+
- Joan MerrillOklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program · 1 of 1 trials Phase 2+
- Y.K.O. TengLeiden University Medical Center · 1 of 1 trials Phase 2+
Registry trials of voclosporin updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 6 of 8 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.
6 trials of drugs against PPP3CA were stopped early; 1 give no reason
Terminated, withdrawn and suspended interventional trials of voclosporin, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 6 most recent of 6.
- terminated · 2026-02-10 · Aurinia Pharmaceuticals Inc. · Voclosporin“DSMB recommendation”
- terminated · 2026-02-10 · Aurinia Pharmaceuticals Inc. · voclosporin“DSMB recommendation”
- terminated · 2025-09-09 · National Institute of Allergy and Infectious Diseases (NIAID) · Voclosporin, Placebo for Voclosporin“The study was closed due to slow enrollment.”
- terminated · 2021-09-16 · Aurinia Pharmaceuticals Inc. · Voclosporin“Low recruitment rate”
- withdrawn · 2014-01-20 · Aurinia Pharmaceuticals Inc. · voclosporinNo reason given
- terminated · 2013-04-17 · Atrium Medical Corporation · matched by the registry's drug synonyms“Terminated ahead of schedule after completion of the 3-year follow-up time point due to Sponsor decision.”
Paediatric incentives and obligations for PPP3CA's drugs
For voclosporin: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · PPP3CA is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000228081 (voclosporin, Treatment of Systemic Lupus Erythematosus (SLE)): PM: decision on the application for modification of an agreed PIP, 19 Mar 2025; EMEA-000132-PIP01-07-M04 (voclosporin, Treatment of non-infectious uveitis): PM: decision on the application for modification of an agreed PIP, 29 Apr 2013Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/12/1085 positive 6 Dec 2012: Treatment of non-infectious uveitisRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/12/1085, 2026-11-11
- Authorised in the EU: yes · Lupkynis: authorised since 15 Sept 2022; Luveniq: application withdrawnRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of voclosporinRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 3 interventional studies of voclosporin include patients under 18; 1 is recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 1 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| VOCLOSPORIN | Protein | phase 4 | lupus nephritis, immune system disorder, psoriasis vulgaris, uveitis, anterior uveitis, dry eye syndrome, kidney disorder, focal segmental glomerulosclerosis, +2 more | Open Targets · ChEMBL |