PPP5C
protein phosphatase 5 catalytic subunit, the group of Protein phosphatase catalytic subunits|Tetratricopeptide repeat domain containing
Basic information
Region (hg38): 19:46347087-46392981
Previous symbols: [ "PPP5" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP5C gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 1 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 26 | 3 | 0 |
Variants in PPP5C
This is a list of pathogenic ClinVar variants found in the PPP5C region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-46347098-T-C | PPP5C-related disorder | Likely benign (Jul 14, 2020) | ||
| 19-46347135-G-GC | PPP5C-related disorder | Uncertain significance (Nov 01, 2023) | ||
| 19-46347137-C-G | not specified | Uncertain significance (Aug 30, 2021) | ||
| 19-46347154-C-G | not specified | Uncertain significance (Jun 12, 2023) | ||
| 19-46347155-C-T | not specified | Uncertain significance (Jun 28, 2023) | ||
| 19-46347164-G-A | not specified | Uncertain significance (Sep 01, 2021) | ||
| 19-46353755-C-G | not specified | Uncertain significance (Dec 14, 2023) | ||
| 19-46353765-G-A | PPP5C-related disorder | Uncertain significance (Sep 09, 2022) | ||
| 19-46353786-G-T | not specified | Uncertain significance (Apr 25, 2023) | ||
| 19-46353810-G-A | not specified | Uncertain significance (Nov 09, 2021) | ||
| 19-46353850-C-T | not specified | Uncertain significance (Dec 01, 2022) | ||
| 19-46353988-C-T | not specified | Uncertain significance (May 31, 2024) | ||
| 19-46375631-G-T | not specified | Uncertain significance (Jul 09, 2021) | ||
| 19-46375666-C-G | not specified | Uncertain significance (Nov 16, 2021) | ||
| 19-46375688-C-T | not specified | Uncertain significance (May 09, 2023) | ||
| 19-46375698-C-G | PPP5C-related disorder | Uncertain significance (May 24, 2023) | ||
| 19-46375703-G-A | not specified | Uncertain significance (Oct 25, 2022) | ||
| 19-46375716-G-A | not specified | Uncertain significance (Mar 07, 2024) | ||
| 19-46375732-G-A | PPP5C-related disorder | Likely benign (Jun 17, 2023) | ||
| 19-46383463-C-T | not specified | Uncertain significance (Jan 29, 2024) | ||
| 19-46384889-A-G | not specified | Uncertain significance (Jan 31, 2024) | ||
| 19-46387103-G-A | PPP5C-related disorder | Likely benign (Apr 29, 2020) | ||
| 19-46387134-G-A | not specified | Uncertain significance (Dec 15, 2022) | ||
| 19-46387162-C-T | not specified | Uncertain significance (May 21, 2024) | ||
| 19-46387224-G-A | not specified | Uncertain significance (Jan 11, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PPP5C | protein_coding | protein_coding | ENST00000012443 | 13 | 45988 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000624 | 125739 | 0 | 3 | 125742 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.73 | 183 | 321 | 0.570 | 0.0000206 | 3294 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000179 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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}.;
- Pathway
- 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;DNA Repair;Signal Transduction;DNA Double-Strand Break Repair;Glucocorticoid receptor regulatory network;ErbB1 downstream signaling;Negative regulation of MAPK pathway;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling by Nuclear Receptors;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;ESR-mediated signaling
(Consensus)
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- loftool
- 0.129
- rvis_EVS
- -0.67
- rvis_percentile_EVS
- 15.76
Haploinsufficiency Scores
- pHI
- 0.586
- hipred
- Y
- hipred_score
- 0.859
- ghis
- 0.662
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ppp5c
- Phenotype
- limbs/digits/tail phenotype; immune system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; neoplasm; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Gene ontology
- Biological process
- MAPK cascade;mitotic cell cycle;negative regulation of protein phosphorylation;DNA repair;transcription, DNA-templated;protein dephosphorylation;response to lead ion;histone dephosphorylation;peptidyl-threonine dephosphorylation;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to morphine;protein heterooligomerization;peptidyl-serine dephosphorylation;cellular response to hydrogen peroxide;cellular response to cadmium ion;negative regulation of neuron death;response to arachidonic acid;positive regulation of glucocorticoid receptor signaling pathway
- Cellular component
- nucleus;nucleoplasm;cytosol;plasma membrane;protein-containing complex;perikaryon;intracellular membrane-bounded organelle;chaperone complex;proximal dendrite
- Molecular function
- G-protein alpha-subunit binding;RNA binding;phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;protein binding;ATP binding;microtubule binding;lipid binding;phosphatase activity;identical protein binding;ADP binding;metal ion binding;tau protein binding;Hsp90 protein binding