PPM1B
protein-codingprotein phosphatase, Mg2+/Mn2+ dependent 1B, 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 has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to cause cell-growth arrest or cell death. Alternative splicing results in multiple transcript variants encoding different isoforms. Additional transcript variants have been described, but currently do not represent full-length sequences. [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 ~76.4 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 PPM1B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002706.6. 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 | 4 | 5 | |||
| missense | 54 | 4 | 58 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 57 | 8 | 0 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002697.1 | 5 | MANE Select | |
| Ensembl | ENSP00000282412.4 | 5 | MANE Select | |
| RefSeq | NP_001028729.1 | 5 | Standard | |
| RefSeq | NP_808907.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MAPK signaling pathway - Homo sapiens (human)
- MAPK Signaling Pathway
- Cytokine Signaling in Immune system
- Immune System
- ISG15 antiviral mechanism
Biological Process
- protein dephosphorylation
- N-terminal protein myristoylation
- negative regulation of interferon-beta production
- peptidyl-threonine dephosphorylation
- negative regulation of I-kappaB kinase/NF-kappaB signaling
Molecular Function
- magnesium ion binding
- protein serine/threonine phosphatase activity
- magnesium-dependent protein serine/threonine phosphatase activity
- protein binding
- manganese ion binding
Cellular Component
- nucleus
- nucleolus
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000282412
- Coding exons
- 5
- Length
- 76416
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.600 | 236 | 263 | 0.896 | 0.0000136 | 3149 |
| Missense (PolyPhen) | 45 | 95.308 | 0.47215 | 1118 | ||
| Synonymous | 0.701 | 83 | 91.5 | 0.907 | 0.00000465 | 915 |
| Loss of Function | 2.68 | 7 | 19.9 | 0.352 | 0.00000116 | 248 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00016 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00011 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Enzyme with a broad specificity. Dephosphorylates CDK2 and CDK6 in vitro. Dephosphorylates PRKAA1 and PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating it at 'Ser- 172'. Plays an important role in the termination of TNF-alpha- mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. {ECO:0000269|PubMed:18930133, ECO:0000269|PubMed:22750291}.;
Recessive Scores
- pRec
- 0.212
Intolerance Scores
- LoFtool
- 0.424
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |