PPP2R3A
protein-codingprotein phosphatase 2 regulatory subunit B''alpha, the group of Protein phosphatase 2 regulatory subunits|EF-hand domain containing
Gene summary
This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]
- PPP2R3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~182.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPP2R3A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002718.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | 5 | 13 | |||
| missense | 163 | 11 | 8 | 182 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 166 | 19 | 14 | 199 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002709.2 | 13 | MANE Select | |
| Ensembl | ENSP00000264977.3 | 13 | MANE Select | |
| RefSeq | NP_001177376.1 | 12 | Standard | |
| RefSeq | NP_871626.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ppp2r3a | Danio rerio | Structure: cardiac muscle cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Dopaminergic synapse - Homo sapiens (human)
- mRNA surveillance pathway - Homo sapiens (human)
- AMPK signaling pathway - Homo sapiens (human)
- Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
Biological Process
- protein dephosphorylation
- regulation of phosphoprotein phosphatase activity
- somite development
Molecular Function
- calcium ion binding
- protein binding
- protein phosphatase regulator activity
Cellular Component
- protein phosphatase type 2A complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264977
- Coding exons
- 13
- Length
- 182219
- Individuals with no LoFs
- 125288
- Homozygous LoFs
- 11
- Heterozygous LoFs
- 448
- Defined
- 125747
- p
- 0.00183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0389 | 591 | 588 | 1.00 | 0.0000287 | 7638 |
| Missense (PolyPhen) | 294 | 305.34 | 0.96285 | 4070 | ||
| Synonymous | -0.145 | 217 | 214 | 1.01 | 0.0000110 | 2106 |
| Loss of Function | 5.00 | 10 | 47.0 | 0.213 | 0.00000239 | 632 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.024 | 0.024 | notable |
| Latino/Admixed American | 0.00084 | 0.00084 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00031 | 0.00031 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- LoFtool
- 0.870
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 74.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.620
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |