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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PPP1R3C
protein phosphatase 1 regulatory subunit 3C
Chromosome 10 · 10q23.32
NCBI Gene: 5507Ensembl: ENSG00000119938.9HGNC: HGNC:9293UniProt: Q9UQK1
36PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingprotein-macromolecule adaptor activityprotein phosphatase bindingprotein phosphatase type 1 complexdisorder of glycogen metabolismintelligencemigraine disorderinjury
✦AI Summary

PPP1R3C (protein phosphatase 1 regulatory subunit 3C) functions as a glycogen-targeting scaffolding subunit for protein phosphatase 1 (PP1), regulating glycogen metabolism and glucose homeostasis. As a regulatory subunit, PPP1R3C activates glycogen synthase while inhibiting glycogen phosphorylase, thereby promoting glycogen synthesis and limiting breakdown 1. The protein dramatically increases basal and insulin-stimulated glycogen synthesis upon overexpression. Mechanistically, PPP1R3C integrates multiple metabolic pathways. It regulates glycolysis and glycolytic capacity in chondrocytes 2 and links glycogen metabolism to thermogenic responses through catecholamine-induced glycogen turnover that generates reactive oxygen species 1. Under stress conditions, PPP1R3C can interact with aryl hydrocarbon receptor to activate glycogenolysis and support pentose phosphate pathway flux for antioxidant NADPH production 3. Clinically, PPP1R3C dysregulation associates with multiple disease states. Low PPP1R3C expression correlates with increased fasting blood glucose in pregnant rats exposed to environmental toxins 4. In cancer, PPP1R3C expression negatively correlates with ovarian cancer survival and stemness 5, while elevated PPP1R3C promotes colorectal cancer progression and rapamycin resistance via mTOR/Myc pathway activation 6. Conversely, miR-4461-mediated PPP1R3C suppression inhibits renal cell carcinoma tumorigenesis 7. These findings establish PPP1R3C as a critical metabolic hub with broad implications for metabolic disease and cancer biology.

Sources cited
1
PPP1R3C regulates glycogen synthesis and turnover in adipocytes; glycogen metabolism links glucose homeostasis to thermogenesis
PMID: 34707293
2
PPP1R3C binds aryl hydrocarbon receptor to activate glycogenolysis and pentose phosphate pathway for ROS clearance
PMID: 38099490
3
Low PPP1R3C expression correlates with increased fasting blood glucose in pregnant rats exposed to PFOS
PMID: 36863164
4
PPP1R3C expression negatively correlates with ovarian cancer patient survival and progression-free survival
PMID: 37511212
5
PPP1R3C suppression via miR-1203 activates mTOR/Myc pathway promoting colorectal cancer progression and rapamycin resistance
PMID: 40263288
6
PPP1R3C regulates glycolysis and integrates cholesterol metabolism with IDH signaling in chondrocytes
PMID: 40232792
7
miR-4461 inhibits renal cell carcinoma tumorigenesis by targeting and downregulating PPP1R3C
PMID: 32915648
Disease Associationsⓘ20
disorder of glycogen metabolismOpen Targets
0.37Weak
intelligenceOpen Targets
0.35Weak
migraine disorderOpen Targets
0.30Weak
injuryOpen Targets
0.29Weak
type 2 diabetes mellitusOpen Targets
0.21Weak
smoking behaviorOpen Targets
0.20Weak
self-injurious ideationOpen Targets
0.15Weak
psoriatic arthritisOpen Targets
0.15Weak
prostate cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
coronary atherosclerosisOpen Targets
0.06Suggestive
type 1 diabetes mellitusOpen Targets
0.06Suggestive
diabetes mellitusOpen Targets
0.05Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.05Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.05Suggestive
chondrosarcomaOpen Targets
0.05Suggestive
glycogen storage disease VIOpen Targets
0.05Suggestive
LIPE-related familial partial lipodystrophyOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NHLRC1Protein interaction95%EPM2AProtein interaction91%PPP1CAProtein interaction91%PPP1CBProtein interaction91%PPP1CCProtein interaction91%STBD1Protein interaction90%
Tissue Expression6 tissues
Heart
100%
Liver
53%
Brain
7%
Lung
4%
Ovary
3%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PPP1R3CNHLRC1EPM2APPP1CAPPP1CBPPP1CCSTBD1
PROTEIN STRUCTURE
Preparing viewer…
PDB7QF7 · 1.47 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.65 [0.46–0.94]
RankingsWhere PPP1R3C stands among ~20K protein-coding genes
  • #10,842of 20,598
    Most Researched36
  • #8,818of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedPPP1R3C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Aryl hydrocarbon receptor sulfenylation promotes glycogenolysis and rescues cancer chemoresistance.
PMID: 38099490
J Clin Invest · 2023
1.00
2
Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis.
PMID: 36863164
Environ Int · 2023
0.90
3
AhRR and PPP1R3C: Potential Prognostic Biomarkers for Serous Ovarian Cancer.
PMID: 37511212
Int J Mol Sci · 2023
0.80
4
Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes.
PMID: 34707293
Nature · 2021
0.70
5
QKI-induced circ_0001766 inhibits colorectal cancer progression and rapamycin resistance by miR-1203/PPP1R3C/mTOR/Myc axis.
PMID: 40263288
Cell Death Discov · 2025
0.60