PPP2R1A

protein phosphatase 2 scaffold subunit Aalpha, the group of Protein phosphatase 2 scaffold subunits|STRIPAK complex|Armadillo like helical domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 19:52170935-52229518

Links

ENSG00000105568 ∙ NCBI:5518 ∙ OMIM:605983 ∙ HGNC:9302 ∙ Uniprot:P30153 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• Houge-Janssens syndrome 2 (Supportive), mode of inheritance: AD
• Houge-Janssens syndrome 2 (Definitive), mode of inheritance: AD
• Houge-Janssens syndrome 2 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Houge-Janssens syndrome 2	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	25533962; 26168268

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP2R1A gene.

• not provided (326 variants)
• Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome (30 variants)
• Inborn genetic diseases (12 variants)
• not specified (9 variants)
• See cases (4 variants)
• Malignant neoplasm of body of uterus (3 variants)
• Uterine carcinosarcoma (3 variants)
• PPP2R1A-related condition (3 variants)
• Ovarian serous cystadenocarcinoma (2 variants)
• Gastric adenocarcinoma (2 variants)
• Lung adenocarcinoma (2 variants)
• Prostate adenocarcinoma (2 variants)
• Squamous cell carcinoma of the head and neck (2 variants)
• Intellectual disability (2 variants)
• Neoplasm of the large intestine (2 variants)
• Breast neoplasm (2 variants)
• PPP2R1A-related neurodevelopmental disorders (1 variants)
• PPP2R1A-related disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder (1 variants)
• 9 conditions (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP2R1A 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			3	102	7	112
missense	4	9	103	9	7	132
nonsense			1			1
start loss						0
frameshift	1		1		1	3
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			6	20	5	31
non coding			3	57	7	67
Total	5	9	113	168	22

Variants in PPP2R1A

This is a list of pathogenic ClinVar variants found in the PPP2R1A region.

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

Position	Type	Phenotype	Significance	ClinVar
19-52190091-GC-G		not specified	Uncertain significance (Oct 28, 2022)
19-52190108-C-T			Likely benign (Jun 18, 2023)
19-52190111-C-G		Houge-Janssens syndrome 2	Uncertain significance (Jul 12, 2019)
19-52190122-C-T		Inborn genetic diseases	Uncertain significance (Dec 06, 2023)
19-52190123-G-T			Likely benign (Jan 16, 2024)
19-52190126-G-A			Likely benign (Nov 27, 2023)
19-52190129-C-T			Likely benign (May 08, 2023)
19-52190132-C-T			Likely benign (May 22, 2023)
19-52190135-C-T			Likely benign (Aug 29, 2022)
19-52190136-G-T			Uncertain significance (Sep 19, 2023)
19-52190146-T-C			Uncertain significance (Oct 17, 2019)
19-52190157-C-T		Inborn genetic diseases	Uncertain significance (May 09, 2022)
19-52190162-T-A			Uncertain significance (Oct 03, 2019)
19-52190169-G-T			Uncertain significance (May 22, 2023)
19-52190171-T-G		not specified • Houge-Janssens syndrome 2	Benign/Likely benign (Oct 14, 2023)
19-52190176-T-C			not provided (-)
19-52190179-G-A			Uncertain significance (Nov 24, 2022)
19-52190181-A-C		not specified	Conflicting classifications of pathogenicity (Jul 24, 2023)
19-52190185-T-C			Benign/Likely benign (Jan 19, 2024)
19-52190187-C-CG			Benign (Jun 16, 2023)
19-52190192-G-T			Likely benign (Nov 27, 2023)
19-52190194-C-T			Likely benign (May 31, 2022)
19-52190204-A-C		not specified	not provided (Sep 19, 2013)
19-52190236-C-G		not specified	not provided (Sep 19, 2013)
19-52190248-ACT-A		not specified	Likely benign (Jan 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP2R1A	protein_coding	protein_coding	ENST00000322088	15	37396

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.984	0.0161	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.46	123	361	0.340	0.0000219	3790
Missense in Polyphen		17	92.642	0.1835		849
Synonymous	0.553	150	159	0.944	0.0000101	1231
Loss of Function	4.42	4	30.2	0.133	0.00000152	334

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)	0.0000620	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887). {ECO:0000269|PubMed:15525651, ECO:0000269|PubMed:16580887}.
• Disease: DISEASE: Mental retardation, autosomal dominant 36 (MRD36) [MIM:616362]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:26168268}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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);mRNA surveillance pathway - 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);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;Generic Transcription Pathway;Metabolism of carbohydrates;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;PP2A-mediated dephosphorylation of key metabolic factors;GPCR Dopamine D1like receptor;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;insulin Mam;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);Regulation of PLK1 Activity at G2/M Transition;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;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;ErbB1 downstream signaling;Hemostasis;MyD88 dependent cascade initiated on endosome;AURKA Activation by TPX2;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;Regulation of TP53 Activity;Transcriptional Regulation by TP53;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Recruitment of NuMA to mitotic centrosomes;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;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;Anchoring of the basal body to the plasma membrane;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;ATR signaling pathway;IL8- and CXCR2-mediated signaling events;insulin;Negative regulation of FGFR1 signaling;Signaling by FGFR1;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.411
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.644
• hipred: Y
• hipred_score: 0.809
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppp2r1a
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; neoplasm; normal 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;inactivation of MAPK activity;regulation of DNA replication;regulation of transcription, DNA-templated;protein dephosphorylation;ceramide metabolic process;apoptotic process;chromosome segregation;female meiotic nuclear division;RNA splicing;response to organic substance;regulation of G2/M transition of mitotic cell cycle;second-messenger-mediated signaling;regulation of Wnt signaling pathway;regulation of cell adhesion;negative regulation of cell growth;regulation of growth;negative regulation of tyrosine phosphorylation of STAT protein;regulation of phosphoprotein phosphatase activity;regulation of cell differentiation;meiotic spindle elongation;mitotic sister chromatid separation;meiotic sister chromatid cohesion, centromeric;protein-containing complex assembly;peptidyl-serine dephosphorylation;ciliary basal body-plasma membrane docking;regulation of meiotic cell cycle process involved in oocyte maturation;positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: protein phosphatase type 2A complex;chromosome, centromeric region;nucleus;cytoplasm;mitochondrion;cytosol;microtubule cytoskeleton;membrane;lateral plasma membrane;dendrite;extracellular exosome;glutamatergic synapse
• Molecular function: protein serine/threonine phosphatase activity;protein binding;protein phosphatase regulator activity;protein heterodimerization activity;protein antigen binding