PPP6C
protein-codingprotein phosphatase 6 catalytic subunit, the group of Protein phosphatase catalytic subunits
Gene summary
This gene encodes the catalytic subunit of protein phosphatase, a component of a signaling pathway regulating cell cycle progression. Splice variants encoding different protein isoforms exist. The pseudogene of this gene is located on chromosome X. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.4 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 PPP6C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002721.5. 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 | 1 | 1 | 2 | |||
| missense | 19 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 31 | 0 | 1 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002712.1 | 7 | MANE Select | |
| Ensembl | ENSP00000362648.4 | 7 | MANE Select | |
| RefSeq | NP_001116827.1 | 8 | Standard | |
| RefSeq | NP_001116841.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
- IL1
Biological Process
- G1/S transition of mitotic cell cycle
- protein dephosphorylation
- innate immune response
- COPII vesicle coating
Molecular Function
- protein serine/threonine phosphatase activity
- protein binding
- metal ion binding
Cellular Component
- Golgi membrane
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000451402
- Coding exons
- 8
- Length
- 43367
- Individuals with no LoFs
- 125558
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 184
- Defined
- 125743
- p
- 0.000736
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.58 | 93 | 194 | 0.479 | 0.0000101 | 2218 |
| Missense (PolyPhen) | 24 | 78.479 | 0.30582 | 945 | ||
| Synonymous | -0.568 | 75 | 69.0 | 1.09 | 0.00000346 | 665 |
| Loss of Function | 3.47 | 3 | 19.5 | 0.154 | 0.00000106 | 224 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000066 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0082 | 0.0073 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000085 | 0.000079 | rare |
| South Asian | 0.0013 | 0.0013 | notable |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalytic subunit of protein phosphatase 6 (PP6). PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation. N-terminal domain restricts G1 to S phase progression in cancer cells, in part through control of cyclin D1. Downregulates MAP3K7 kinase activation of the IL1 signaling pathway by dephosphorylation of MAP3K7. Participates also in the innate immune defense against viruses by desphosphorylating RIG-I/DDX58, an essential step that triggers RIG-I/DDX58-mediated signaling activation. {ECO:0000269|PubMed:10227379, ECO:0000269|PubMed:17079228, ECO:0000269|PubMed:17568194, ECO:0000269|PubMed:29053956, ECO:0000269|PubMed:9013334}.;
Recessive Scores
- pRec
- 0.338
Intolerance Scores
- LoFtool
- 0.272
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.75
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.584
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |