PPP2R5D (Q14738) variants and mutations

PPP2R5D (also known as Q14738) is a human protein-coding gene encoding a serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform protein. It directs the PP2A phosphatase toward specific signaling substrates in neurons and other cells, helping control phosphorylation-dependent growth and synaptic pathways. De novo pathogenic variants cause Jordan's syndrome, with developmental delay, intellectual disability, hypotonia, and often macrocephaly. This analysis covers 709 PPP2R5D variants and mutations. Of these, 90% have computational variant effect predictions. Disease context includes Hogue-Janssens syndrome 1, Intellectual disability, and cancer. Example PPP2R5D variants include P2S, P2T, and P2P.

Variant analysis overview

Gene: PPP2R5D
Protein: Q14738
UniProt accession: Q14738
Organism: Homo sapiens
Variants analyzed: 709
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 499 unspecified-consequence records; 79 missense variants; 104 synonymous variants; 9 frameshift variants; 8 in-frame deletions; 2 in-frame insertions; 2 stop-gained variants; 1 splice-region variants; 5 substitution
Prediction scores: 641 variants have prediction scores (90% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Hogue-Janssens syndrome 1, Intellectual disability, cancer, neurodegenerative disease, hereditary disease, genetic developmental and epileptic encephalopathy, chronic myelogenous leukemia, BCR-ABL1 positive, complex neurodevelopmental disorder, neurodevelopmental disorder, Neurodevelopmental delay, Global developmental delay, Neurodevelopmental abnormality.

Protein structure and variant hotspots

Protein features: 6 post-translational modification sites.
PTM context: 11 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable PPP2R5D variants

Examples include P2S, P2T, P2P, Y3F, Y3H, Y3Y, K4E, K4N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

PPP2R5D analysis run — PPP2R5D (709 variants) — completed 2026-08-19