PPP3CA

Chr 4

protein phosphatase 3 catalytic subunit alpha

Also known as: ACCIID, CALN, CALNA, CALNA1, CNA1, DEE91, IECEE, IECEE1

NCBI Gene: 5530 ENSG00000138814 UniProt: Q08209

The protein is a calcium-dependent, calmodulin-stimulated phosphatase that dephosphorylates multiple substrates involved in transcription, mitochondrial dynamics, and cellular signaling pathways. Mutations cause developmental and epileptic encephalopathy 91 as well as arthrogryposis with cleft palate, craniosynostosis, and intellectual disability, inherited in an autosomal dominant pattern. This gene is extremely intolerant to loss-of-function variants (pLI=1.0, LOEUF=0.16), indicating that even single functional copies are insufficient for normal development.

ResearchSummary from RefSeq, OMIM, UniProt

Enables several functions, including ATPase binding activity; calmodulin binding activity; and calmodulin-dependent protein phosphatase activity. Involved in several processes, including calcineurin-NFAT signaling cascade; negative regulation of angiotensin-activated signaling pathway; and peptidyl-serine dephosphorylation. Located in cytoplasm; cytoplasmic side of plasma membrane; and dendritic spine. Part of calcineurin complex. Implicated in developmental and epileptic encephalopathy 91. Biomarker of cholangiocarcinoma; focal segmental glomerulosclerosis; and schizophrenia. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEpileptic encephalopathy, infantile or early childhood, 1

UniProtArthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development

Clinical highlights

Gene-disease validity (ClinGen)

developmental and epileptic encephalopathy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.16

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429