PPP2CA

protein phosphatase 2 catalytic subunit alpha, the group of Protein phosphatase catalytic subunits|STRIPAK complex

Basic information

Region (hg38): 5:134193978-134226073

Links

ENSG00000113575 ∙ NCBI:5515 ∙ OMIM:176915 ∙ HGNC:9299 ∙ Uniprot:P67775 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Houge-Janssens syndrome 3 (Moderate), mode of inheritance: AD
• Houge-Janssens syndrome 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Houge-Janssens syndrome 3	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	30595372

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP2CA gene.

• not provided (9 variants)
• Houge-Janssens syndrome 3 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP2CA 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				58	1	59
missense	1	13	42	3	1	60
nonsense	4	1				5
start loss	1		1			2
frameshift	6	3				9
inframe indel		2	3			5
splice donor/acceptor (+/-2bp)	1	1				2
splice region			3	11	1	15
non coding			3	26	5	34
Total	13	20	49	87	7

Variants in PPP2CA

This is a list of pathogenic ClinVar variants found in the PPP2CA region.

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

Position	Type	Phenotype	Significance	ClinVar
5-134197765-AAT-A		PPP2CA-related disorder	Likely benign (May 28, 2019)
5-134197777-GGAA-G		Malignant tumor of prostate	Uncertain significance (-)
5-134197777-G-GGAA		Houge-Janssens syndrome 3	Likely pathogenic (Jul 15, 2019)
5-134197782-T-C			Uncertain significance (Sep 27, 2019)
5-134197796-A-T			Likely benign (May 01, 2023)
5-134197813-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2022)
5-134197814-G-A			Likely benign (Jan 06, 2024)
5-134197839-T-G			Uncertain significance (Oct 03, 2023)
5-134197852-A-G			Likely benign (Apr 25, 2023)
5-134197859-C-A			Likely benign (Jul 25, 2023)
5-134197859-C-T			Likely benign (Jul 06, 2021)
5-134197860-G-A			Likely benign (Oct 05, 2023)
5-134199064-ATG-A			Likely benign (Oct 17, 2022)
5-134199066-G-C			Likely benign (Nov 28, 2023)
5-134199069-C-G			Likely benign (Apr 09, 2023)
5-134199072-G-A			Likely benign (Nov 08, 2022)
5-134199088-A-G			Likely benign (Feb 05, 2022)
5-134199091-G-A			Likely benign (Apr 28, 2021)
5-134199091-G-C			Pathogenic (Oct 13, 2023)
5-134199097-T-C			Likely benign (Jan 29, 2024)
5-134199101-G-GTT			Pathogenic (Oct 28, 2022)
5-134199106-G-A			Benign/Likely benign (Apr 01, 2024)
5-134199117-T-C			Uncertain significance (Apr 25, 2021)
5-134199121-T-G			Likely benign (Dec 06, 2023)
5-134199127-T-C			Likely benign (Jun 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP2CA	protein_coding	protein_coding	ENST00000481195	7	31809

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0107	123598	0	2	123600	0.00000809

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.15	24	181	0.132	0.0000100	2021
Missense in Polyphen		1	65.33	0.015307		800
Synonymous	-1.43	75	60.8	1.23	0.00000307	584
Loss of Function	3.72	1	18.1	0.0554	9.63e-7	198

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)	0.00000904	0.00000900
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000164	0.000164

dbNSFP

Source: dbNSFP

• Function: FUNCTION: PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'. {ECO:0000250, ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:22613722, ECO:0000269|PubMed:9920888}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Long-term depression - Homo sapiens (human);Tight junction - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);mRNA surveillance pathway - Homo sapiens (human);Autophagy - other - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;WNT-Ncore;Sphingolipid Metabolism;TNF alpha Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Dopamine metabolism;Mesodermal Commitment Pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Wnt Signaling Pathway and Pluripotency;PI3K-Akt Signaling Pathway;Glycogen Metabolism;Signaling by GPCR;Negative regulation of FGFR2 signaling;Signaling by FGFR2;Degradation of beta-catenin by the destruction complex;RAF activation;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Negative regulation of FGFR3 signaling;Signaling by FGFR3;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Inhibition of replication initiation of damaged DNA by RB1/E2F1;Signaling by Interleukins;Negative regulation of FGFR4 signaling;Signaling by FGFR4;Signaling by FGFR;Spry regulation of FGF signaling;regulation of eif-4e and p70s6 kinase;akt signaling pathway;Generic Transcription Pathway;Metabolism of carbohydrates;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;PP2A-mediated dephosphorylation of key metabolic factors;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;CTLA4 inhibitory signaling;Costimulation by the CD28 family;MASTL Facilitates Mitotic Progression;RNA Polymerase II Transcription;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;Innate Immune System;Immune System;Metabolism;Cyclin D associated events in G1;G1 Phase;Adaptive Immune System;RHO GTPases Activate Formins;E2F mediated regulation of DNA replication;Mitotic G1-G1/S phases;Nuclear Events (kinase and transcription factor activation);Disassembly of the destruction complex and recruitment of AXIN to the membrane;Cyclin A/B1/B2 associated events during G2/M transition;DARPP-32 events;Glycolysis;RHO GTPase Effectors;Signaling by Rho GTPases;ERKs are inactivated;Signaling by NTRK1 (TRKA);Signaling by NTRKs;ERK/MAPK targets;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;ErbB1 downstream signaling;Hemostasis;MyD88 dependent cascade initiated on endosome;Negative regulation of MAPK pathway;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;G2/M Transition;Mitotic G2-G2/M phases;PIP3 activates AKT signaling;G1/S Transition;Beta-catenin phosphorylation cascade;Mitotic Prophase;IL3;C-MYC pathway;Regulation of TP53 Activity;Transcriptional Regulation by TP53;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Mitotic Prometaphase;Separation of Sister Chromatids;Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Opioid Signalling;G alpha (i) signalling events;M Phase;Glucose metabolism;Cell Cycle;Wnt;Resolution of Sister Chromatid Cohesion;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;Integration of energy metabolism;Platelet sensitization by LDL;Platelet homeostasis;Cell Cycle, Mitotic;GPCR downstream signalling;Intracellular signaling by second messengers;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;PLK1 signaling events;TCF dependent signaling in response to WNT;PDGFR-beta signaling pathway;Regulation of retinoblastoma protein;ATR signaling pathway;IL8- and CXCR2-mediated signaling events;TGF-beta receptor signaling;p53 pathway;Negative regulation of FGFR1 signaling;Signaling by FGFR1 (Consensus)

Recessive Scores

• pRec: 0.292

Intolerance Scores

• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.889
• hipred: Y
• hipred_score: 0.831
• ghis: 0.678

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.931

Mouse Genome Informatics

• Gene name: Ppp2ca
• Phenotype: liver/biliary system phenotype; embryo phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; hematopoietic system 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; reproductive system phenotype

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;inactivation of MAPK activity;regulation of protein phosphorylation;regulation of DNA replication;regulation of transcription, DNA-templated;protein dephosphorylation;ceramide metabolic process;apoptotic process;mesoderm development;RNA splicing;response to organic substance;response to lead ion;negative regulation of epithelial to mesenchymal transition;second-messenger-mediated signaling;regulation of Wnt signaling pathway;regulation of cell adhesion;negative regulation of cell growth;peptidyl-threonine dephosphorylation;regulation of growth;negative regulation of tyrosine phosphorylation of STAT protein;regulation of cell differentiation;meiotic cell cycle;peptidyl-serine dephosphorylation;positive regulation of protein serine/threonine kinase activity;regulation of microtubule binding;positive regulation of microtubule binding
• Cellular component: protein phosphatase type 2A complex;chromosome, centromeric region;spindle pole;nucleus;mitochondrion;cytosol;plasma membrane;microtubule cytoskeleton;membrane;membrane raft;synapse;extracellular exosome
• Molecular function: phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;protein binding;protein C-terminus binding;metal ion binding;protein heterodimerization activity;tau protein binding;GABA receptor binding