PPP2R3C
protein-codingprotein phosphatase 2 regulatory subunit B''gamma, the group of Protein phosphatase 2 regulatory subunits
Gene summary
This gene encodes a regulatory subunit of the serine/threonine phosphatase, protein phosphatase 2. This protein is localized to both nuclear and cytoplasmic regions depending on cell cycle phase. Homozygous conditional knockout mice for this gene exhibit reduced numbers and impaired proliferation of immune system B cells. This protein may regulate the expression of the P-glycoprotein ATP-binding cassette transporter through its phosphatase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]
- C14orf10
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032738
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0032739
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032738
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0032738
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPP2R3C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017917.4. 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 | 3 | 3 | ||||
| missense | 4 | 59 | 1 | 64 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 3 | 5 | |||
| Total | 4 | 2 | 67 | 4 | 0 | 77 |
Highest pathogenic variant AF is 0.000076709395
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060387.2 | 13 | MANE Select | |
| Ensembl | ENSP00000261475.5 | 13 | MANE Select | |
| RefSeq | NP_001292084.1 | 10 | Standard | |
| RefSeq | NP_001292085.1 | 10 | Standard |
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
- microtubule cytoskeleton organization
- B cell homeostasis
- regulation of antimicrobial humoral response
- cortical cytoskeleton organization
- activation of protein kinase activity
Molecular Function
- protein binding
- metal ion binding
Cellular Component
- nucleus
- Golgi apparatus
- centrosome
- spindle
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261475
- Coding exons
- 13
- Length
- 37051
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 50
- Defined
- 125747
- p
- 0.000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 168 | 225 | 0.747 | 0.0000108 | 3008 |
| Missense (PolyPhen) | 51 | 72.51 | 0.70335 | 1015 | ||
| Synonymous | -0.830 | 90 | 80.5 | 1.12 | 0.00000407 | 777 |
| Loss of Function | 1.72 | 17 | 26.6 | 0.640 | 0.00000112 | 374 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.000094 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00022 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May regulate MCM3AP phosphorylation through phosphatase recruitment. May act as a negative regulator of ABCB1 expression and function through the dephosphorylation of ABCB1 by TFPI2/PPP2R3C complex. May play a role in the activation-induced cell death of B-cells. {ECO:0000250|UniProtKB:Q9JK24, ECO:0000269|PubMed:24333728}.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- LoFtool
- 0.530
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.25
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.941
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |