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: P62140

The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Noonan syndrome-like disorder with loose anagen hair 2MIM #617506
AD
1
Active trials
26
Pathogenic / LP
297
ClinVar variants
18
Pubs (1 yr)
4.3
Missense Z· constrained
0.15
LOEUF· LoF intolerant
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

⚡
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.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 61 VUS of 297 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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
LOF
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

297 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic10
VUS61
Likely Benign182
Benign22
Conflicting6
16
Pathogenic
10
Likely Pathogenic
61
VUS
182
Likely Benign
22
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
13
0
16
Likely Pathogenic
0
9
1
0
10
VUS
3
38
19
1
61
Likely Benign
0
0
94
88
182
Benign
0
0
20
2
22
Conflicting
—6
Total35014791297

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

PPP1CB · protein map & ClinVar variants

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

Gene2Phenotype Curations

PPP1CB-related rasopathy with developmental delay, short stature, and sparse slow-growing hair

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
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
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
Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease STAT3 Signaling Pathway.
Zhou Y et al.·Adv Sci (Weinh)
2024
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
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
Ras-MAPK pathway in patients with lupus nephritis.
Zhang C et al.·Lupus Sci Med
2025Cohort
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