PPP4R1

protein-coding

protein phosphatase 4 regulatory subunit 1, the group of Armadillo like helical domain containing|Protein phosphatase 4 regulatory subunits

Gene summary

This gene encodes one of several alternate regulatory subunits of serine/threonine protein phosphatase 4 (PP4). The protein features multiple HEAT repeats. This protein forms a complex with PP4RC. This complex may have a distinct role from other PP4 complexes, including regulation of HDAC3 (Zhang et al., PMID: 15805470). There is also a transcribed pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

MANE transcript

NM_001042388.3

Inheritance

—

ClinVar variants

U:140B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr18:9,546,791-9,615,240

External References & Databases

Ensembl (ENSG00000154845)

Transcript & Mutation Effects

hg38 • Region Span ~68.4 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 PPP4R1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 125

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001042388.3. 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			3 clinvar			3
missense			129 clinvar	2 clinvar		131
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	140	2	0	142

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001042388.3	RefSeq	NP_001035847.1	20	MANE Select
ENST00000400556.8	Ensembl	ENSP00000383402.3	20	MANE Select
NM_001382562.1	RefSeq	NP_001369491.1	17	Standard
NM_005134.4	RefSeq	NP_005125.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
protein dephosphorylation
signal transduction
regulation of phosphoprotein phosphatase activity

Molecular Function

phosphoprotein phosphatase activity
protein serine/threonine phosphatase activity
protein binding
protein phosphatase regulator activity

Cellular Component

protein phosphatase 4 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000400556
Coding exons: 20
Length: 68450
Individuals with no LoFs: 124780
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 124794
p: 0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.04	382	512	0.746	0.0000270	6261
Missense (PolyPhen)		110	185.72	0.59228		2233
Synonymous	1.03	169	187	0.904	0.0000106	1785
Loss of Function	5.68	6	48.8	0.123	0.00000275	589

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000071	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of serine/threonine-protein phosphatase 4. May play a role in regulation of cell division in renal glomeruli. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. {ECO:0000269|PubMed:15805470}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.363
RVIS EVS: 0.09
RVIS percentile EVS: 60.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.691

Gene Damage Prediction

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