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

ENSG00000156475 ∙ NCBI:5521 ∙ OMIM:604325 ∙ HGNC:9305 ∙ Uniprot:Q00005 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 12 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 12 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the PPP2R2B gene.

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.

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		3
missense			30	5		35
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding				3	8	11
Total	0	0	33	11	8

Variants in PPP2R2B

This is a list of pathogenic ClinVar variants found in the PPP2R2B region.

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

Position	Type	Phenotype	Significance	ClinVar
5-146589999-A-G		Global developmental delay	Uncertain significance (Sep 27, 2022)
5-146590061-G-A			Likely benign (Aug 01, 2024)
5-146590066-T-C		not specified	Uncertain significance (Oct 01, 2023)
5-146590066-T-G		not specified	Uncertain significance (Jul 07, 2022)
5-146590089-C-G			Uncertain significance (Jan 05, 2017)
5-146590094-C-A			Likely benign (Jun 01, 2024)
5-146590096-C-A		not specified	Uncertain significance (Dec 19, 2022)
5-146590125-C-T		not specified	Uncertain significance (May 23, 2023)
5-146590165-C-G			Uncertain significance (Apr 25, 2023)
5-146592977-G-A		not specified	Uncertain significance (Mar 14, 2023)
5-146593059-G-T			Uncertain significance (May 05, 2022)
5-146600310-C-T		not specified	Uncertain significance (May 24, 2023)
5-146600311-G-A		not specified	Uncertain significance (Feb 17, 2024)
5-146600321-G-T		Neurodevelopmental disorder	Uncertain significance (-)
5-146600341-C-T			Likely benign (Apr 01, 2024)
5-146600343-G-A			Uncertain significance (Sep 26, 2023)
5-146600431-T-C			Uncertain significance (Apr 25, 2023)
5-146600439-G-C		not specified	Uncertain significance (Jan 23, 2023)
5-146600448-G-A		not specified	Uncertain significance (Jul 26, 2022)
5-146638304-G-T		Spinocerebellar ataxia type 12	Uncertain significance (Nov 02, 2021)
5-146638334-T-C			Uncertain significance (Sep 01, 2018)
5-146638376-G-A		PPP2R2B-related disorder	Likely benign (Aug 07, 2020)
5-146650558-T-C		not specified	Uncertain significance (May 17, 2023)
5-146650601-C-A		PPP2R2B-related disorder	Likely benign (Jun 06, 2019)
5-146650623-G-A		PPP2R2B-related disorder	Likely benign (Jun 11, 2019)

GnomAD

Source: gnomAD

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: dbNSFP

• 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