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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PPP1CB
protein phosphatase 1 catalytic subunit beta
Chromosome 2 Β· 2p23.2
NCBI Gene: 5500Ensembl: ENSG00000213639.12HGNC: HGNC:9282UniProt: P62140
300PubMed Papers
21Diseases
0Drugs
14Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
chromosome, telomeric regionregulation of circadian rhythmPTW/PP1 phosphatase complexcytosolNoonan syndrome-like disorder with loose anagen hair 2Noonan syndrome-like disorder with loose anagen hairNoonan syndromeneurodegenerative disease
✦AI Summary

PPP1CB (protein phosphatase 1 catalytic subunit beta) is a serine/threonine phosphatase that functions as a catalytic component of multiple regulatory complexes controlling diverse biological processes. As a core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex, PPP1CB dephosphorylates inhibitory phosphorylation sites on RAF family kinases (RAF1 at Ser-259, BRAF at Ser-365, ARAF at Ser-214), thereby stimulating MAPK pathway activation 123. PPP1CB also participates in the PTW/PP1 phosphatase complex regulating chr2 structure and cell cycle progression, and modulates circadian rhythm through PER1 and PER2 dephosphorylation [UniProt annotations]. Beyond MAPK signaling, PPP1CB has documented roles in lung adenocarcinoma glycolysis suppression via STAT3 dephosphorylation 4 and in immune regulation, including FOXP3 dephosphorylation in regulatory T cells [UniProt]. Clinically, PPP1CB mutations are associated with Noonan syndrome and Noonan syndrome-like disorders 5, intellectual disability 6, and lupus nephritis with RASopathy features 7. PPP1CB emerges as a diagnostic candidate gene in osteoporosis with sarcopenia 8 and rheumatoid arthritis 9, suggesting broader disease relevance beyond developmental disorders.

Sources cited
1
PPP1CB is core component of SMP complex that dephosphorylates RAF kinases to activate MAPK pathway
PMID: 35768504
2
PPP1CB in SMP complex dephosphorylates RAF family kinases at specific inhibitory sites
PMID: 35831509
3
SMP complex enhances PPP1CB dephosphorylation activity and substrate specificity
PMID: 36175670
4
PPP1CB dephosphorylates p-STAT3 to suppress HK2-dependent glycolysis in lung adenocarcinoma
PMID: 39119928
5
LZTR1 binds to RAF1-PPP1CB complex; PPP1CB mutations cause Noonan syndrome with cardiac defects
PMID: 30368668
6
De novo PPP1CB mutations identified as possibly pathogenic in moderate to severe intellectual disability
PMID: 25356899
7
PPP1CB expression elevated in kidney and PBMC of lupus nephritis patients with RASopathy mutations
PMID: 40102014
8
PPP1CB identified as T cell-related diagnostic feature in rheumatoid arthritis through machine learning analysis
PMID: 38962008
9
PPP1CB identified as candidate hub gene for diagnosing osteoporosis combined with sarcopenia
PMID: 38831425
Disease Associationsβ“˜21
Noonan syndrome-like disorder with loose anagen hair 2Open Targets
0.75Strong
Noonan syndrome-like disorder with loose anagen hairOpen Targets
0.72Strong
Noonan syndromeOpen Targets
0.58Moderate
neurodegenerative diseaseOpen Targets
0.56Moderate
rasopathyOpen Targets
0.52Moderate
Abnormality of the cardiovascular systemOpen Targets
0.50Moderate
neuroinflammatory disorderOpen Targets
0.45Moderate
Abnormality of the skeletal systemOpen Targets
0.43Moderate
obesityOpen Targets
0.38Weak
genetic disorderOpen Targets
0.37Weak
esophageal carcinomaOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.36Weak
Alzheimer diseaseOpen Targets
0.36Weak
Parkinson diseaseOpen Targets
0.36Weak
multiple sclerosisOpen Targets
0.36Weak
Neurodevelopmental delayOpen Targets
0.34Weak
skin diseaseOpen Targets
0.28Weak
Intellectual disabilityOpen Targets
0.27Weak
Dandy-Walker syndromeOpen Targets
0.26Weak
ovarian dysfunctionOpen Targets
0.23Weak
Noonan syndrome-like disorder with loose anagen hair 2UniProt
Pathogenic Variants14
NM_002709.3(PPP1CB):c.820G>A (p.Glu274Lys)Likely pathogenic
Noonan syndrome-like disorder with loose anagen hair 2|PPP1CB-related disorder|RASopathy|not provided
β˜…β˜…β˜…β˜†2024β†’ Residue 274
NM_002709.3(PPP1CB):c.548A>T (p.Glu183Val)Pathogenic
not provided|Noonan syndrome-like disorder with loose anagen hair 2|RASopathy|Cardiovascular phenotype
β˜…β˜…β˜…β˜†2024β†’ Residue 183
NM_002709.3(PPP1CB):c.548A>C (p.Glu183Ala)Pathogenic
Noonan syndrome-like disorder with loose anagen hair 2|not provided|RASopathy|Cardiovascular phenotype|Noonan syndrome-like disorder with loose anagen hair
β˜…β˜…β˜…β˜†2024β†’ Residue 183
NM_002709.3(PPP1CB):c.166G>C (p.Ala56Pro)Likely pathogenic
Noonan syndrome-like disorder with loose anagen hair 2|RASopathy
β˜…β˜…β˜…β˜†2024β†’ Residue 56
NM_002709.3(PPP1CB):c.146C>G (p.Pro49Arg)Pathogenic
not provided|Noonan syndrome-like disorder with loose anagen hair 2|Noonan syndrome|Dandy-Walker syndrome|Inborn genetic diseases|Neurodevelopmental delay|RASopathy|Cardiovascular phenotype
β˜…β˜…β˜…β˜†2024β†’ Residue 49
NM_002709.3(PPP1CB):c.545T>A (p.Met182Lys)Pathogenic
Noonan syndrome|Noonan syndrome-like disorder with loose anagen hair 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 182
NM_002709.3(PPP1CB):c.658C>T (p.Arg220Cys)Pathogenic
not provided|Noonan syndrome-like disorder with loose anagen hair 2
β˜…β˜…β˜†β˜†2022β†’ Residue 220
NM_002709.3(PPP1CB):c.569G>A (p.Arg190Lys)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 190
NM_002709.3(PPP1CB):c.493G>A (p.Asp165Asn)Likely pathogenic
Noonan syndrome-like disorder with loose anagen hair 2
β˜…β˜†β˜†β˜†2023β†’ Residue 165
NM_002709.3(PPP1CB):c.493G>C (p.Asp165His)Likely pathogenic
Noonan syndrome-like disorder with loose anagen hair 2
β˜…β˜†β˜†β˜†2022β†’ Residue 165
NM_002709.3(PPP1CB):c.755A>G (p.Asp252Gly)Likely pathogenic
Cardiovascular phenotype
β˜…β˜†β˜†β˜†2021β†’ Residue 252
NM_002709.3(PPP1CB):c.515A>G (p.His172Arg)Likely pathogenic
Intellectual disability
β˜…β˜†β˜†β˜†2019β†’ Residue 172
NM_002709.3(PPP1CB):c.255C>A (p.Asn85Lys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 85
NM_002709.3(PPP1CB):c.754G>T (p.Asp252Tyr)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 252
View on ClinVar β†—
Related Genes
EIF2S1Protein interaction100%WDR33Protein interaction100%CPSF1Protein interaction100%INTS1Protein interaction100%PPP1R13LProtein interaction100%ANKRD28Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
59%
Lung
42%
Bone Marrow
37%
Ovary
36%
Liver
17%
Gene Interaction Network
Click a node to explore
PPP1CBEIF2S1WDR33CPSF1INTS1PPP1R13LANKRD28
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P62140
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.25Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.08 [0.03–0.25]
RankingsWhere PPP1CB stands among ~20K protein-coding genes
  • #1,168of 20,598
    Most Researched300 Β· top 10%
  • #2,493of 5,498
    Most Pathogenic Variants14
  • #745of 17,882
    Most Constrained (LOEUF)0.25 Β· top 5%
Genes detectedPPP1CB
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Integrated analysis of single-cell RNA-seq, bulk RNA-seq, Mendelian randomization, and eQTL reveals T cell-related nomogram model and subtype classification in rheumatoid arthritis.
PMID: 38962008
Front Immunol Β· 2024
1.00
2
Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1-PPP1CB complexes.
PMID: 30368668
Hum Genet Β· 2019
0.90
3
Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease STAT3 Signaling Pathway.
PMID: 39119928
Adv Sci (Weinh) Β· 2024
0.80
4
Identification of shared gene signatures and pathways for diagnosing osteoporosis with sarcopenia through integrated bioinformatics analysis and machine learning.
PMID: 38831425
BMC Musculoskelet Disord Β· 2024
0.70
5
Chromosomal localization of human, rat, and mouse protein phosphatase type 1 beta catalytic subunit genes (PPP1CB) by fluorescence in situ hybridization.
PMID: 7857673
Jpn J Genet Β· 1994
0.64