PPM1L
protein-codingprotein phosphatase, Mg2+/Mn2+ dependent 1L, the group of Protein phosphatases, Mg2+/Mn2+ dependent
Gene summary
The protein encoded by this gene is a magnesium or manganese-requiring phosphatase that is involved in several signaling pathways. The encoded protein downregulates apoptosis signal-regulating kinase 1, a protein that initiates a signaling cascade that leads to apoptosis when cells are subjected to cytotoxic stresses. This protein also is an endoplasmic reticulum transmembrane protein that helps regulate ceramide transport from the endoplasmic reticulum to the Golgi apparatus. Finally, this gene may be involved in adiposity since it is upregulated in adipose tissues. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~323.3 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 PPM1L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_139245.4. 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 | 0 | |||||
| missense | 37 | 37 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 38 | 0 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_640338.2 | 4 | MANE Select | |
| Ensembl | ENSP00000417659.1 | 4 | MANE Select | |
| RefSeq | NP_001304840.1 | 4 | Standard | |
| RefSeq | NP_001304841.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amino Acid metabolism
- Metabolism of lipids
- Metabolism
- Sphingolipid de novo biosynthesis
- Sphingolipid metabolism
Biological Process
- MAPK cascade
- protein dephosphorylation
- transmembrane receptor protein serine/threonine kinase signaling pathway
- sphingolipid biosynthetic process
Molecular Function
- protein serine/threonine phosphatase activity
- magnesium-dependent protein serine/threonine phosphatase activity
- metal ion binding
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000498165
- Coding exons
- 4
- Length
- 323306
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.06 | 123 | 206 | 0.596 | 0.0000103 | 2377 |
| Missense (PolyPhen) | 36 | 73.821 | 0.48767 | 811 | ||
| Synonymous | -0.187 | 86 | 83.8 | 1.03 | 0.00000450 | 688 |
| Loss of Function | 2.80 | 3 | 14.5 | 0.207 | 8.31e-7 | 159 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6. {ECO:0000269|PubMed:17456047}.;
Recessive Scores
- pRec
- 0.167
Intolerance Scores
- LoFtool
- 0.250
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.22
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.450
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |