PPP1R15A

protein-coding

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

Gene summary

This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014330.5

Inheritance

—

ClinVar variants

U:102B:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr19:48,872,212-48,876,059

External References & Databases

Ensembl (ENSG00000087074)

Transcript & Mutation Effects

hg38 • Region Span ~3.8 kb

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GenCC 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 PPP1R15A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 111

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014330.5. 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			1 clinvar	1 clinvar	2 clinvar	4
missense			99 clinvar	14 clinvar		113
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	102	15	2	119

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014330.5	RefSeq	NP_055145.3	2	MANE Select
ENST00000200453.6	Ensembl	ENSP00000200453.4	2	MANE Select
ENST00000600406.2	Ensembl	ENSP00000469239.2	1	Standard
ENST00000704026.1	Ensembl	ENSP00000515636.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
TGF-Ncore
Photodynamic therapy-induced unfolded protein response
Signal Transduction
TGF_beta_Receptor

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

Molecular Function

protein binding
protein phosphatase 1 binding
protein phosphatase regulator activity
protein kinase binding
protein phosphatase activator activity

Cellular Component

protein phosphatase type 1 complex
cytoplasm
mitochondrion
mitochondrial outer membrane
endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000200453
Coding exons: 2
Length: 3666
Individuals with no LoFs: 122881
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 122885
p: 0.0000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.158	391	382	1.02	0.0000203	4296
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000091	0.0000090	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.195

Intolerance Scores

LoFtool: 0.946
RVIS EVS: 2.56
RVIS percentile EVS: 98.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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