PPP5C
protein-codingprotein phosphatase 5 catalytic subunit, the group of Protein phosphatase catalytic subunits|Tetratricopeptide repeat domain containing
Gene summary
This gene encodes a serine/threonine phosphatase which is a member of the protein phosphatase catalytic subunit family. Proteins in this family participate in pathways regulated by reversible phosphorylation at serine and threonine residues; many of these pathways are involved in the regulation of cell growth and differentiation. The product of this gene has been shown to participate in signaling pathways in response to hormones or cellular stress, and elevated levels of this protein may be associated with breast cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]
- PPP5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPP5C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006247.4. 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 | 2 | 1 | 3 | |||
| missense | 47 | 1 | 48 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 54 | 3 | 0 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006238.1 | 13 | MANE Select | |
| Ensembl | ENSP00000012443.4 | 13 | MANE Select | |
| RefSeq | NP_001191213.1 | 12 | Standard | |
| Ensembl | ENSP00000375786.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MAPK signaling pathway - Homo sapiens (human)
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- MAPK Signaling Pathway
- ATM Signaling Network in Development and Disease
Biological Process
- MAPK cascade
- mitotic cell cycle
- negative regulation of protein phosphorylation
- DNA repair
- transcription, DNA-templated
Molecular Function
- G-protein alpha-subunit binding
- RNA binding
- phosphoprotein phosphatase activity
- protein serine/threonine phosphatase activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- plasma membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000012443
- Coding exons
- 13
- Length
- 45988
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125742
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.73 | 183 | 321 | 0.570 | 0.0000206 | 3294 |
| Missense (PolyPhen) | 41 | 133.13 | 0.30797 | 1334 | ||
| Synonymous | 0.372 | 125 | 130 | 0.959 | 0.00000928 | 905 |
| Loss of Function | 4.75 | 2 | 30.1 | 0.0664 | 0.00000160 | 327 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT. Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses. Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress. Plays a positive role in adipogenesis, mainly through the dephosphorylation and activation of PPARG transactivation function. Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1. Regulates the circadian rhythms, through the dephosphorylation and activation of CSNK1E. May modulate TGF-beta signaling pathway by the regulation of SMAD3 phosphorylation and protein expression levels. Dephosphorylates and may play a role in the regulation of TAU/MAPT. Through their dephosphorylation, may play a role in the regulation of ions channels such as KCNH2. {ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22399290, ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:9000529}.;
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- LoFtool
- 0.129
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |