PPP1CB

protein phosphatase 1 catalytic subunit beta, the group of Protein phosphatase catalytic subunits

Basic information

Region (hg38): 2:28751639-28802940

Links

ENSG00000213639 ∙ NCBI:5500 ∙ OMIM:600590 ∙ HGNC:9282 ∙ Uniprot:P62140 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Noonan syndrome-like disorder with loose anagen hair 2 (Strong), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair 2 (Strong), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair 2 (Strong), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair (Supportive), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Noonan syndrome-like disorder with loose anagen hair 2	AD	Cardiovascular	Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and valvular anomalies) can be beneficial	Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic	25356899; 27264673; 27681385; 27868344; 28211982

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP1CB gene.

• not provided (171 variants)
• Cardiovascular phenotype (29 variants)
• Noonan syndrome-like disorder with loose anagen hair 2 (9 variants)
• not specified (7 variants)
• Inborn genetic diseases (7 variants)
• PPP1CB-related condition (4 variants)
• Noonan syndrome (4 variants)
• Dandy-Walker syndrome (1 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP1CB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	54	1	56
missense	3	6	28			37
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			5	9		14
non coding			1	63	12	76
Total	3	6	31	117	13

Variants in PPP1CB

This is a list of pathogenic ClinVar variants found in the PPP1CB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-28751664-A-C			Likely benign (Feb 21, 2019)
2-28751725-C-G			Benign (Nov 10, 2018)
2-28751757-C-G			Benign (May 26, 2021)
2-28751800-G-A			Benign (Aug 04, 2020)
2-28751817-G-A			Benign (Jun 26, 2021)
2-28752031-C-T			Likely benign (Mar 24, 2021)
2-28752102-G-A			Likely benign (Aug 04, 2019)
2-28752124-G-C			Uncertain significance (Feb 01, 2023)
2-28752129-C-T		Cardiovascular phenotype	Uncertain significance (Oct 26, 2023)
2-28752130-G-A			not provided (-)
2-28752134-G-A			not provided (-)
2-28752136-G-A			Likely benign (Jan 26, 2024)
2-28752137-G-C			Uncertain significance (Jul 10, 2023)
2-28752140-C-G			Uncertain significance (Oct 18, 2022)
2-28752144-A-C			Uncertain significance (Jan 20, 2024)
2-28752145-C-A			Uncertain significance (Nov 27, 2021)
2-28752145-C-T		Cardiovascular phenotype	Likely benign (Oct 15, 2023)
2-28752151-C-T		Cardiovascular phenotype • not specified	Benign/Likely benign (Feb 01, 2024)
2-28752154-C-T		Cardiovascular phenotype • not specified	Likely benign (Nov 20, 2023)
2-28752155-C-G		Noonan syndrome	Uncertain significance (Jul 09, 2021)
2-28752157-C-T		Cardiovascular phenotype	Likely benign (Sep 11, 2022)
2-28752162-C-T			Uncertain significance (Apr 12, 2022)
2-28752163-C-T		Cardiovascular phenotype	Likely benign (Mar 05, 2024)
2-28752166-G-C		PPP1CB-related disorder	Likely benign (Jul 19, 2022)
2-28752167-C-T		Cardiovascular phenotype	Likely benign (Aug 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP1CB	protein_coding	protein_coding	ENST00000395366	8	51301

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000883	125711	0	3	125714	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.33	17	181	0.0939	0.00000950	2132
Missense in Polyphen		1	77.35	0.012928		992
Synonymous	0.938	52	61.3	0.848	0.00000299	605
Loss of Function	4.18	0	20.4	0.00	0.00000130	237

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T- cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). {ECO:0000269|PubMed:20516061, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208}.
• Disease: DISEASE: Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2) [MIM:617506]: A syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair. {ECO:0000269|PubMed:27264673, ECO:0000269|PubMed:27681385, ECO:0000269|PubMed:27868344, ECO:0000269|PubMed:28211982}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);mRNA surveillance pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Common Pathways Underlying Drug Addiction;Focal Adhesion;G13 Signaling Pathway;Signal Transduction;Circadian Clock;Metabolism of lipids;Metabolism;RHO GTPases Activate ROCKs;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases activate CIT;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Triglyceride catabolism;Triglyceride metabolism;G2/M Transition;Mitotic G2-G2/M phases;Cell Cycle;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Cell Cycle, Mitotic;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs;PLK1 signaling events (Consensus)

Intolerance Scores

• loftool: 0.222
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.758
• hipred: Y
• hipred_score: 0.739
• ghis: 0.638

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Ppp1cb
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: ppp1cb
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: shortened

Gene ontology

• Biological process: glycogen metabolic process;protein dephosphorylation;cell cycle;regulation of cell adhesion;circadian regulation of gene expression;regulation of circadian rhythm;entrainment of circadian clock by photoperiod;cell division
• Cellular component: protein phosphatase type 1 complex;nuclear chromosome, telomeric region;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;plasma membrane;focal adhesion;extracellular exosome;PTW/PP1 phosphatase complex
• Molecular function: protein serine/threonine phosphatase activity;protein binding;phosphatase activity;myosin phosphatase activity;protein kinase binding;metal ion binding;myosin-light-chain-phosphatase activity