PPP3R1

protein-coding

protein phosphatase 3 regulatory subunit B, alpha, the group of EF-hand domain containing|Protein phosphatase 3 regulatory subunits

Gene summary

Enables phosphatase binding activity and protein domain specific binding activity. Involved in calcineurin-NFAT signaling cascade and positive regulation of transcription by RNA polymerase II. Located in plasma membrane. Part of calcineurin complex. Implicated in Alzheimer's disease and dilated cardiomyopathy. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_000945.4

Inheritance

ClinVar variants

U:5

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr2:68,178,857-68,256,237

External References & Databases

Ensembl (ENSG00000221823)

Transcript & Mutation Effects

hg38 • Region Span ~77.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant nonsyndromic hearing loss 58LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014293

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPP3R1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 2

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000945.4. 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			1 clinvar			1
missense			2 clinvar			2
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	5	0	0	5

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000945.4	RefSeq	NP_000936.1	6	MANE Select
ENST00000234310.8	Ensembl	ENSP00000234310.3	6	MANE Select
ENST00000409377.1	Ensembl	ENSP00000387148.1	5	Standard
ENST00000409377.2	Ensembl	ENSP00000387148.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxytocin signaling pathway - Homo sapiens (human)
T cell receptor signaling pathway - Homo sapiens (human)
B cell receptor signaling pathway - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
VEGF signaling pathway - Homo sapiens (human)

Biological Process

protein dephosphorylation
Wnt signaling pathway, calcium modulating pathway
calcineurin-NFAT signaling cascade
Fc-epsilon receptor signaling pathway
positive regulation of transcription by RNA polymerase II

Molecular Function

calcium-dependent protein serine/threonine phosphatase activity
calcium ion binding
protein binding
calmodulin binding
cyclosporin A binding

Cellular Component

nucleoplasm
cytosol
calcineurin complex
sarcolemma

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000234310
Coding exons: 6
Length: 77381
Individuals with no LoFs: 124538
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 124544
p: 0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.89	10	84.8	0.118	0.00000380	1147
Missense (PolyPhen)		1	27.524	0.036332		385
Synonymous	1.02	23	30.1	0.764	0.00000151	283
Loss of Function	2.25	2	9.48	0.211	4.83e-7	123

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00010	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000029	0.000027	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity. {ECO:0000269|PubMed:26794871}.;

Intolerance Scores

RVIS EVS: 0.08
RVIS percentile EVS: 59.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.486