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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP2R2C
protein phosphatase 2 regulatory subunit Bgamma
Chromosome 4 · 4p16.1
NCBI Gene: 5522Ensembl: ENSG00000074211.14HGNC: HGNC:9306UniProt: Q9Y2T4
58PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingprotein phosphatase regulator activitycytosolprotein phosphatase type 2A complexneurodegenerative diseaseVaricose veinsmultiple sclerosistype 2 diabetes mellitus
✦AI Summary

PPP2R2C encodes the B-gamma regulatory subunit of protein phosphatase 2A (PP2A), which modulates substrate selectivity and catalytic activity of the phosphatase complex 1. This brain-abundant subunit shows unique expression patterns, with high levels in brain tissue and nearly undetectable expression in other tissues 1. Functionally, PPP2R2C plays crucial roles in multiple cellular processes. In embryonic stem cells, it participates in a PP2A complex that reduces Erk1/2 activity, contributing to the regulation of pluripotency through Netrin-1 signaling pathways 2. The protein also regulates tau dephosphorylation and PP2A activity, with expression being downregulated in Alzheimer's disease mouse models, suggesting involvement in neurodegeneration 3. Clinically, PPP2R2C disruption is associated with autosomal dominant intellectual disability, epilepsy, and behavioral problems 4, while genetic variants are linked to ADHD and personality traits 5. In cancer contexts, PPP2R2C functions as a tumor suppressor, being downregulated in gliomas, nasopharyngeal carcinoma, and ovarian cancers 678. When overexpressed, it inhibits cancer cell proliferation through mTOR pathway suppression by enhancing PP2A-S6K complex formation 6.

Sources cited
1
PPP2R2C encodes B-gamma regulatory subunit of PP2A with brain-specific expression
PMID: 10945473
2
PPP2R2C participates in PP2A complex that reduces Erk1/2 activity in pluripotency regulation
PMID: 32231305
3
PPP2R2C regulates tau dephosphorylation and is downregulated in Alzheimer's disease models
PMID: 32291379
4
PPP2R2C disruption causes autosomal dominant intellectual disability with epilepsy and behavioral problems
PMID: 20601260
5
PPP2R2C genetic variants are associated with ADHD and personality traits
PMID: 22664926
6
PPP2R2C functions as tumor suppressor in gliomas through mTOR pathway suppression
PMID: 24126060
7
PPP2R2C is downregulated in nasopharyngeal carcinoma
PMID: 28525724
8
PPP2R2C is downregulated in ovarian cancer
PMID: 26796271
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.51Moderate
Varicose veinsOpen Targets
0.33Weak
multiple sclerosisOpen Targets
0.32Weak
type 2 diabetes mellitusOpen Targets
0.32Weak
insomniaOpen Targets
0.31Weak
protozoa infectious diseaseOpen Targets
0.31Weak
placenta praeviaOpen Targets
0.26Weak
COVID-19Open Targets
0.24Weak
adrenal gland hyperfunctionOpen Targets
0.23Weak
hyperaldosteronismOpen Targets
0.23Weak
diabetes mellitusOpen Targets
0.23Weak
pericarditisOpen Targets
0.23Weak
Alzheimer diseaseOpen Targets
0.07Suggestive
astrocytomaOpen Targets
0.06Suggestive
gliomaOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.04Suggestive
esophageal adenocarcinomaOpen Targets
0.04Suggestive
pancreatic adenocarcinomaOpen Targets
0.03Suggestive
atypical teratoid rhabdoid tumorOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCT8Protein interaction100%TCP1Protein interaction100%CCT5Protein interaction99%CCT2Protein interaction99%CCT4Protein interaction99%CCT7Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Heart
8%
Ovary
1%
Liver
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PPP2R2CCCT8TCP1CCT5CCT2CCT4CCT7
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9Y2T4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.38Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.22 [0.14–0.38]
RankingsWhere PPP2R2C stands among ~20K protein-coding genes
  • #7,906of 20,598
    Most Researched58
  • #1,773of 17,882
    Most Constrained (LOEUF)0.38 · top 10%
Genes detectedPPP2R2C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PPP2R2C as a candidate gene of a temperament and character trait-based endophenotype of ADHD.
PMID: 22664926
Atten Defic Hyperact Disord · 2012
1.00
2
Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling.
PMID: 32231305
Nat Cell Biol · 2020
0.90
3
Interaction between miR-572 and PPP2R2C, and their effects on the proliferation, migration, and invasion of nasopharyngeal carcinoma (NPC) cells.
PMID: 28525724
Biochem Cell Biol · 2017
0.80
4
Molecular cloning and mapping of the brain-abundant B1gamma subunit of protein phosphatase 2A, PPP2R2C, to human chromosome 4p16.
PMID: 10945473
Genomics · 2000
0.70
5
PP2A subunit PPP2R2C is downregulated in the brains of Alzheimer's transgenic mice.
PMID: 32291379
Aging (Albany NY) · 2020
0.60