PPP2R2B
protein phosphatase 2 regulatory subunit Bbeta, the group of WD repeat domain containing|Protein phosphatase 2 regulatory subunits
Basic information
Region (hg38): 5:146580742-147084784
Previous symbols: [ "SCA12" ]
Links
Phenotypes
GenCC
Source:
- spinocerebellar ataxia type 12 (Supportive), mode of inheritance: AD
- spinocerebellar ataxia type 12 (Strong), mode of inheritance: AD
- spinocerebellar ataxia type 12 (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Spinocerebellar ataxia 12 | 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 | Neurologic | 10581021; 11719278; 14526180; 16138911; 20301381; 20629122 |
| The condition involves expansion of triplet repeats |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (30 variants)
- not_provided (29 variants)
- PPP2R2B-related_disorder (6 variants)
- Spinocerebellar_ataxia_type_12 (5 variants)
- Neurodevelopmental_disorder (1 variants)
- Global_developmental_delay (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP2R2B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181675.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | |||||
| missense | 49 | 54 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 0 | 0 | 52 | 8 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PPP2R2B | protein_coding | protein_coding | ENST00000336640 | 9 | 496412 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.985 | 0.0153 | 125739 | 0 | 8 | 125747 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.25 | 167 | 271 | 0.616 | 0.0000159 | 3004 |
| Missense in Polyphen | 28 | 84.741 | 0.33042 | 988 | ||
| Synonymous | 0.447 | 96 | 102 | 0.944 | 0.00000615 | 812 |
| Loss of Function | 3.90 | 2 | 21.5 | 0.0930 | 0.00000119 | 245 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000580 | 0.0000580 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000354 | 0.0000352 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
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. Within the PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic activity (By similarity). Isoform 2 regulates neuronal survival through the mitochondrial fission and fusion balance (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Spinocerebellar ataxia 12 (SCA12) [MIM:604326]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA). {ECO:0000269|PubMed:10581021}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Dopaminergic synapse - 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;GPCR Dopamine D1like receptor;insulin Mam;PDGFR-beta signaling pathway;ATR signaling pathway;insulin
(Consensus)
Recessive Scores
- pRec
- 0.246
Intolerance Scores
- loftool
- 0.720
- rvis_EVS
- -0.74
- rvis_percentile_EVS
- 13.94
Haploinsufficiency Scores
- pHI
- 0.928
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.670
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.866
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ppp2r2b
- Phenotype
- hematopoietic system phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- mitotic cell cycle;apoptotic process;regulation of phosphoprotein phosphatase activity;peptidyl-serine dephosphorylation
- Cellular component
- protein phosphatase type 2A complex;mitochondrion;mitochondrial outer membrane;cytosol;cytoskeleton
- Molecular function
- protein serine/threonine phosphatase activity;protein binding;protein phosphatase regulator activity