PPP1CB

Chr 2AD

protein phosphatase 1 catalytic subunit beta

Also known as: HEL-S-80p, MP, NSLH2, PP-1B, PP1B, PP1Cbeta, PP1Cdelta, PP1beta

NCBI Gene: 5500ENSG00000213639UniProt: P62140OMIM: 600590

The protein is a catalytic subunit of protein phosphatase 1 that dephosphorylates numerous cellular targets and is essential for cell division, glycogen metabolism, muscle contractility, synaptic plasticity, and MAPK pathway regulation. Mutations cause Noonan syndrome-like disorder with loose anagen hair 2 with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.147), indicating that functional copies are critical for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.151 OMIM phenotype
VCEP Guidelines: RASopathyReleased
View SpecificationsClinGen Panel
Clinical Summary— PPP1CB
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Gene-Disease Validity (ClinGen)
Noonan syndrome-like disorder with loose anagen hair · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.15LOEUF
pLI 0.999
Z-score 4.18
OE 0.00 (0.00–0.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
4.33Z-score
OE missense 0.09 (0.06–0.14)
17 obs / 181.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.15)
0≤0.351.4
Missense OE0.09 (0.06–0.14)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 0 / 20.3Missense obs/exp: 17 / 181.0Syn Z: 0.94
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePPP1CB-related rasopathy with developmental delay, short stature, and sparse slow-growing hairOTHERAD
DN
0.3793th %ile
GOF
0.3689th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.15

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PPP1CB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The expression and clinical prognostic value of protein phosphatase 1 catalytic subunit beta in pancreatic cancer
Hu L et al.·Bioengineered
2021
Differentially expressed mRNAs of neural signaling pathway genes in peripheral blood leukocytes as biomarkers for schizophrenia
Zhou Y et al.·Schizophrenia (Heidelb)
2025
Identification of shared gene signatures and pathways for diagnosing osteoporosis with sarcopenia through integrated bioinformatics analysis and machine learning
Zhou X et al.·BMC Musculoskelet Disord
2024
Genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma.
Zhong Y et al.·Cancer Genet
2021
Noonan syndrome with loose anagen hair with variants in the PPP1CB gene: First familial case reported.
Huckstadt V et al.·Am J Med Genet A
2021Case report
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Engineered targeting OIP5 sensitizes bladder cancer to chemotherapy resistance via TRIP12-PPP1CB-YBX1 axis.
Wang X et al.·Oncogene
2024
Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.
Yao Z et al.·Nat Metab
2023
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.
Ding Q et al.·Front Immunol
2024Functional
The recurrent PPP1CB mutation p.Pro49Arg in an additional Noonan-like syndrome individual: Broadening the clinical phenotype.
Bertola D et al.·Am J Med Genet A
2017Review
Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1-PPP1CB complexes.
Umeki I et al.·Hum Genet
2019Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients