PPP4R2

protein-coding

protein phosphatase 4 regulatory subunit 2, the group of Protein phosphatase 4 regulatory subunits

Gene summary

The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

MANE transcript

NM_174907.4

Inheritance

—

ClinVar variants

U:49B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr3:72,996,803-73,069,198

External References & Databases

Ensembl (ENSG00000163605)

Transcript & Mutation Effects

hg38 • Region Span ~72.4 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 PPP4R2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 105

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_174907.4. 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						0
missense			49 clinvar	3 clinvar		52
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	49	3	0	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_174907.4	RefSeq	NP_777567.1	9	MANE Select
ENST00000356692.10	Ensembl	ENSP00000349124.5	9	MANE Select
NM_001318025.2	RefSeq	NP_001304954.1	8	Standard
NM_001318026.2	RefSeq	NP_001304955.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
DNA Repair
DNA Double-Strand Break Repair
Homology Directed Repair
Processing of DNA double-strand break ends

Biological Process

mRNA processing
cellular protein modification process
protein dephosphorylation
RNA splicing
regulation of double-strand break repair via homologous recombination

Molecular Function

protein binding
protein phosphatase regulator activity
protein binding, bridging

Cellular Component

nucleus
nucleoplasm
cytoplasm
centrosome
protein phosphatase 4 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356692
Coding exons: 9
Length: 72415
Individuals with no LoFs: 125678
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125683
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.000893	206	206	1.00	0.00000978	2774
Missense (PolyPhen)		36	53.738	0.66992		789
Synonymous	-1.81	90	70.6	1.27	0.00000360	738
Loss of Function	4.00	0	18.7	0.00	9.92e-7	265

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4). May regulate the activity of PPP4C at centrosomal microtubule organizing centers. Its interaction with the SMN complex leads to enhance the temporal localization of snRNPs, suggesting a role of PPP4C in maturation of spliceosomal snRNPs. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AFX phosphorylated on 'Ser-140' (gamma-H2AFX) generated during DNA replication and required for DNA double strand break repair. Mediates RPA2 dephosphorylation by recruiting PPP4C to RPA2 in a DNA damage-dependent manner. RPA2 dephosphorylation is required for the efficient RPA2-mediated recruitment of RAD51 to chromatin following double strand breaks, an essential step for DNA repair. {ECO:0000269|PubMed:10769191, ECO:0000269|PubMed:12668731, ECO:0000269|PubMed:18614045, ECO:0000269|PubMed:20154705}.;

Recessive Scores

pRec: 0.0956

Intolerance Scores

LoFtool: 0.192
RVIS EVS: 0.22
RVIS percentile EVS: 68.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.761

Gene Damage Prediction

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