PPP5C

protein phosphatase 5 catalytic subunit, the group of Protein phosphatase catalytic subunits|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 19:46347086-46392981

Previous symbols: [ "PPP5" ]

Links

ENSG00000011485 ∙ NCBI:5536 ∙ OMIM:600658 ∙ HGNC:9322 ∙ Uniprot:P53041 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP5C gene.

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		2
missense			25			25
nonsense						0
start loss				1		1
frameshift			1			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: gnomAD

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: dbNSFP

• 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