PPM1F
protein-codingprotein phosphatase, Mg2+/Mn2+ dependent 1F, the group of Protein phosphatases, Mg2+/Mn2+ dependent
Gene summary
The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase can interact with Rho guanine nucleotide exchange factors (PIX), and thus block the effects of p21-activated kinase 1 (PAK), a protein kinase mediating biological effects downstream of Rho GTPases. Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G/CAMK-II) is found to be one of the substrates of this phosphatase. The overexpression of this phosphatase or CAMK2G has been shown to mediate caspase-dependent apoptosis. An alternatively spliced transcript variant has been identified, but its full-length nature has not been determined. [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 ~33.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0001751
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPM1F variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014634.4. 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 | 24 | 5 | 32 | ||
| missense | 91 | 4 | 4 | 99 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 97 | 28 | 9 | 134 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055449.1 | 7 | MANE Select | |
| Ensembl | ENSP00000263212.5 | 7 | MANE Select | |
| RefSeq | NP_001397765.1 | 5 | Standard | |
| Ensembl | ENSP00000380632.4 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ppm1f | Danio rerio | Structure: whole organism Quality: apoptotic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of protein kinase activity
- positive regulation of gene expression
- positive regulation of epithelial cell migration
- positive regulation of cell-substrate adhesion
- histone dephosphorylation
Molecular Function
- protein serine/threonine phosphatase activity
- magnesium-dependent protein serine/threonine phosphatase activity
- protein binding
- protein tyrosine/serine/threonine phosphatase activity
- calmodulin-dependent protein phosphatase activity
Cellular Component
- cytosol
- protein-containing complex
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263212
- Coding exons
- 7
- Length
- 33417
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125736
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.31 | 224 | 286 | 0.782 | 0.0000184 | 2908 |
| Missense (PolyPhen) | 60 | 108.68 | 0.5521 | 1085 | ||
| Synonymous | 0.989 | 113 | 127 | 0.888 | 0.00000904 | 950 |
| Loss of Function | 2.34 | 7 | 17.6 | 0.398 | 8.39e-7 | 186 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dephosphorylates and concomitantly deactivates CaM- kinase II activated upon autophosphorylation, and CaM-kinases IV and I activated upon phosphorylation by CaM-kinase kinase. Promotes apoptosis.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.652
- RVIS EVS
- -0.02
- RVIS percentile EVS
- 52.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |