PPP1R15A

protein phosphatase 1 regulatory subunit 15A, the group of Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 19:48872212-48876059

Links

ENSG00000087074 ∙ NCBI:23645 ∙ OMIM:611048 ∙ HGNC:14375 ∙ Uniprot:O75807 ∙ 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 PPP1R15A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP1R15A 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			41	7		48
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	41	7	2

Variants in PPP1R15A

This is a list of pathogenic ClinVar variants found in the PPP1R15A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-48873240-C-T		not specified	Uncertain significance (Jul 12, 2023)
19-48873243-G-T		not specified	Uncertain significance (Sep 08, 2024)
19-48873284-C-A		not specified	Uncertain significance (Apr 15, 2024)
19-48873315-C-T		not specified	Likely benign (Dec 13, 2021)
19-48873354-C-T		not specified	Uncertain significance (Mar 06, 2023)
19-48873399-G-A		not specified	Uncertain significance (Jun 30, 2023)
19-48873424-C-T		not specified	Uncertain significance (Aug 15, 2023)
19-48873427-G-T		not specified	Uncertain significance (Apr 26, 2023)
19-48873439-C-T		not specified	Uncertain significance (Aug 04, 2024)
19-48873444-C-T		not specified	Uncertain significance (Dec 22, 2023)
19-48873451-C-T		not specified	Uncertain significance (Oct 25, 2022)
19-48873465-C-T		not specified	Likely benign (Aug 20, 2024)
19-48873618-G-A		not specified	Uncertain significance (Jun 02, 2023)
19-48873640-A-G		not specified	Uncertain significance (Nov 21, 2023)
19-48873648-C-T		not specified	Uncertain significance (Dec 28, 2023)
19-48873663-C-G		not specified	Uncertain significance (May 17, 2023)
19-48873720-G-A		not specified	Uncertain significance (Oct 20, 2024)
19-48873735-G-T		not specified	Uncertain significance (Jan 18, 2023)
19-48873742-A-T		not specified	Uncertain significance (Dec 12, 2022)
19-48873785-G-A			Benign (May 31, 2018)
19-48873786-G-C		not specified	Uncertain significance (Dec 27, 2023)
19-48873801-G-A		not specified	Uncertain significance (Sep 12, 2023)
19-48873844-A-C		not specified	Likely benign (Dec 01, 2024)
19-48873853-C-T		not specified	Uncertain significance (May 26, 2024)
19-48873883-C-T		not specified	Uncertain significance (Jan 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP1R15A	protein_coding	protein_coding	ENST00000200453	2	3666

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.21e-12	0.125	122881	0	4	122885	0.0000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.158	391	382	1.02	0.0000203	4296
Missense in Polyphen		178	166.51	1.069		1840
Synonymous	-0.875	164	150	1.09	0.00000800	1428
Loss of Function	0.674	20	23.5	0.850	0.00000125	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000595	0.0000595
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000914	0.00000903
Middle Eastern	0.00	0.00
South Asian	0.0000329	0.0000328
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15'. {ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:12556489, ECO:0000269|PubMed:14635196, ECO:0000269|PubMed:14718519, ECO:0000269|PubMed:8139541}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);TGF-Ncore;Photodynamic therapy-induced unfolded protein response;Signal Transduction;TGF_beta_Receptor;BMP receptor signaling;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs;TGF-beta receptor signaling (Consensus)

Recessive Scores

• pRec: 0.195

Intolerance Scores

• loftool: 0.946
• rvis_EVS: 2.56
• rvis_percentile_EVS: 98.74

Haploinsufficiency Scores

• pHI: 0.0292
• hipred: N
• hipred_score: 0.352

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Ppp1r15a
• Phenotype: cellular phenotype; hematopoietic 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); immune system phenotype

Gene ontology

• Biological process: apoptotic process;cellular response to DNA damage stimulus;cell cycle arrest;positive regulation of translational initiation in response to stress;negative regulation of phosphoprotein phosphatase activity;positive regulation of phosphoprotein phosphatase activity;response to endoplasmic reticulum stress;negative regulation of protein dephosphorylation;regulation of translational initiation by eIF2 alpha dephosphorylation;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;protein localization to endoplasmic reticulum;positive regulation of peptidyl-serine dephosphorylation;negative regulation of PERK-mediated unfolded protein response;positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation
• Cellular component: protein phosphatase type 1 complex;cytoplasm;mitochondrion;mitochondrial outer membrane;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;cytosol;membrane
• Molecular function: protein binding;protein phosphatase 1 binding;protein phosphatase regulator activity;protein kinase binding;protein phosphatase activator activity