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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP1CC
protein phosphatase 1 catalytic subunit gamma
Chromosome 12 · 12q24.11
NCBI Gene: 5501Ensembl: ENSG00000186298.12HGNC: HGNC:9283UniProt: P36873
313PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
chromosome, telomeric regionnucleoplasmnucleuscytoplasmNoonan syndromeesophageal carcinomaaortic stenosisneurodegenerative disease
✦AI Summary

PPP1CC encodes protein phosphatase 1 catalytic subunit gamma, a serine/threonine phosphatase that forms highly specific holoenzymes with over 200 regulatory proteins to dephosphorylate hundreds of biological targets 1. The gene undergoes tissue-specific splicing, producing a ubiquitously expressed isoform (PPP1CC1) and a testis-enriched, sperm-specific isoform (PPP1CC2) essential for spermatogenesis completion 1. PPP1CC plays critical roles in multiple cellular processes including DNA repair, where it promotes nonhomologous end joining (NHEJ) by binding Ku70/Ku80 heterodimers and activating DNA-PKcs, leading to radioresistance in nasopharyngeal carcinoma 2. The protein regulates cell death pathways by dephosphorylating RIPK1 through recruitment by PPP1R3G, promoting both apoptosis and necroptosis 3. Additionally, PPP1CC functions as a tumor suppressor in cell competition by integrating apoptosis and ferroptosis-like cell death via JNK signaling activation 4. The gene is located on chromosome 12.1-q24.2 5 and shows associations with muscle strength phenotypes 6 and platelet regulation in immune thrombocytopenia 7. These diverse functions highlight PPP1CC's importance in cellular homeostasis, cancer biology, and potential therapeutic applications.

Sources cited
1
PPP1CC encodes a serine/threonine phosphatase with tissue-specific splicing producing testis-specific and ubiquitous isoforms
PMID: 25620225
2
PPP1CC promotes NHEJ-mediated DNA repair and radioresistance by binding Ku70/Ku80 and activating DNA-PKcs
PMID: 38589496
3
PPP1CC regulates cell death by dephosphorylating RIPK1 when recruited by PPP1R3G
PMID: 34862394
4
PPP1CC acts as tumor suppressor integrating apoptosis and ferroptosis-like cell death via JNK signaling
PMID: 40906558
5
PPP1CC gene is located on chromosome 12q24.1-q24.2
PMID: 8394140
6
PPP1CC shows associations with muscle strength phenotypes
PMID: 21750233
7
PPP1CC is associated with platelet regulation in immune thrombocytopenia
PMID: 41175382
Disease Associationsⓘ20
Noonan syndromeOpen Targets
0.46Moderate
esophageal carcinomaOpen Targets
0.37Weak
aortic stenosisOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.26Weak
Precordial painOpen Targets
0.24Weak
Increased blood pressureOpen Targets
0.19Weak
intelligenceOpen Targets
0.15Weak
azoospermiaOpen Targets
0.10Weak
partial chromosome Y deletionOpen Targets
0.09Suggestive
spermatogenic failure 25Open Targets
0.08Suggestive
spermatogenic failure 50Open Targets
0.08Suggestive
spermatogenic failure 57Open Targets
0.08Suggestive
spermatogenic failure 78Open Targets
0.08Suggestive
spermatogenic failure 63Open Targets
0.08Suggestive
spermatogenic failure 71Open Targets
0.08Suggestive
spermatogenic failure 54Open Targets
0.08Suggestive
spermatogenic failure 65Open Targets
0.08Suggestive
spermatogenic failure 48Open Targets
0.08Suggestive
spermatogenic failure 84Open Targets
0.08Suggestive
spermatogenic failure 93Open Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EIF2S1Protein interaction100%WDR33Protein interaction100%PPP1R13LProtein interaction100%WWTR1Protein interaction100%PPP1R9AProtein interaction100%CNSTProtein interaction100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
88%
Brain
81%
Ovary
61%
Lung
48%
Liver
37%
Gene Interaction Network
Click a node to explore
PPP1CCEIF2S1WDR33PPP1R13LWWTR1PPP1R9ACNST
PROTEIN STRUCTURE
Preparing viewer…
PDB5INB · 1.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.58Moderately Constrained
pLIⓘ
0.83Intermediate
Observed/Expected LoF0.34 [0.21–0.58]
RankingsWhere PPP1CC stands among ~20K protein-coding genes
  • #1,086of 20,598
    Most Researched313 · top 10%
  • #3,906of 17,882
    Most Constrained (LOEUF)0.58 · top quartile
Genes detectedPPP1CC
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma.
PMID: 38589496
Cell Death Differ · 2024
1.00
2
Pp1-87B/PPP1CC-JNK axis integrates apoptosis and ferroptosis-like cell death to regulate cell competition and tumorigenesis.
PMID: 40906558
Cell Rep · 2025
0.90
3
RIPK1 dephosphorylation and kinase activation by PPP1R3G/PP1γ promote apoptosis and necroptosis.
PMID: 34862394
Nat Commun · 2021
0.80
4
Oral vitamin D supplementation induces transcriptomic changes in rectal mucosa that are linked to anti-tumour effects.
PMID: 34340708
BMC Med · 2021
0.76
5
Sequence of human protein serine/threonine phosphatase 1 gamma and localization of the gene (PPP1CC) encoding it to chromosome bands 12q24.1-q24.2.
PMID: 8394140
Biochim Biophys Acta · 1993
0.70