PPP1R1A

protein-coding

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

Gene summary

Predicted to enable protein serine/threonine phosphatase inhibitor activity. Predicted to be involved in intracellular signal transduction. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_006741.4

Inheritance

—

ClinVar variants

U:28B:2

Top phenotype

Rosette-forming glioneuronal tumor

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr12:54,575,387-54,588,659

External References & Databases

Ensembl (ENSG00000135447)

Transcript & Mutation Effects

hg38 • Region Span ~13.3 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 PPP1R1A variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 22

not providedTotal: 1

Rosette-forming glioneuronal tumorTotal: 1

Low-frequency sensorineural hearing impairmentTotal: 1

Low-frequency hearing lossTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006741.4. 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 clinvar			2
missense			24 clinvar	2 clinvar		26
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	28	2	0	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006741.4	RefSeq	NP_006732.3	7	MANE Select
ENST00000257905.13	Ensembl	ENSP00000257905.8	7	MANE Select
ENST00000547431.5	Ensembl	ENSP00000473304.1	6	Standard
ENST00000547431.6	Ensembl	ENSP00000473304.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Long-term potentiation - Homo sapiens (human)
Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
Common Pathways Underlying Drug Addiction

Biological Process

glycogen metabolic process
negative regulation of phosphoprotein phosphatase activity
intracellular signal transduction

Molecular Function

protein serine/threonine phosphatase inhibitor activity
protein binding

Cellular Component

extracellular space
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257905
Coding exons: 7
Length: 13273
Individuals with no LoFs: 124645
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 124654
p: 0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.977	66	92.4	0.714	0.00000518	1080
Missense (PolyPhen)		28	38.255	0.73194		470
Synonymous	-0.628	36	31.5	1.14	0.00000160	330
Loss of Function	1.59	4	9.21	0.435	3.93e-7	119

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000060	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibitor of protein-phosphatase 1. This protein may be important in hormonal control of glycogen metabolism. Hormones that elevate intracellular cAMP increase I-1 activity in many tissues. I-1 activation may impose cAMP control over proteins that are not directly phosphorylated by PKA. Following a rise in intracellular calcium, I-1 is inactivated by calcineurin (or PP2B). Does not inhibit type-2 phosphatases.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.736
RVIS EVS: 0.61
RVIS percentile EVS: 83.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0370

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium