PPP6R2

protein-coding

protein phosphatase 6 regulatory subunit 2, the group of Armadillo like helical domain containing|Protein phosphatase 6 regulatory subunits

Gene summary

The protein encoded by this gene is a regulatory protein for the protein phosphatase-6 catalytic subunit. Together, these proteins act as a significant T-loop phosphatase for Aurora A, an essential mitotic kinase. Loss of function of either the regulatory or catalytic subunit of protein phosphatase-6 interferes with spindle formation and chromosome alignment. [provided by RefSeq, May 2017]

Previous symbols:

KIAA0685
SAPS2

MANE transcript

NM_001242898.2

Inheritance

—

ClinVar variants

U:168B:19

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr22:50,343,304-50,445,090

External References & Databases

Ensembl (ENSG00000100239)

Transcript & Mutation Effects

hg38 • Region Span ~101.8 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 PPP6R2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 166

not providedTotal: 9

Prostate cancerTotal: 1

Charcot-Marie-Tooth disease type 4B3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001242898.2. 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	6 clinvar		7
missense			159 clinvar	13 clinvar		172
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	168	19	0	187

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 252 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001242898.2	RefSeq	NP_001229827.1	22	MANE Select
ENST00000612753.5	Ensembl	ENSP00000478417.1	22	MANE Select
NM_001242899.2	RefSeq	NP_001229828.1	21	Standard
NM_001242900.2	RefSeq	NP_001229829.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395741
Coding exons: 21
Length: 101782
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.934	514	577	0.891	0.0000357	6093
Missense (PolyPhen)		113	183.38	0.61621		2168
Synonymous	-0.527	262	251	1.04	0.0000178	1861
Loss of Function	4.51	10	41.3	0.242	0.00000203	471

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. Involved in the PP6- mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha. {ECO:0000269|PubMed:16769727}.;

Recessive Scores

pRec: 0.0893

Intolerance Scores

RVIS EVS: 0.7
RVIS percentile EVS: 85.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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