PPP2R3A

Chr 3

protein phosphatase 2 regulatory subunit B''alpha

Also known as: PPP2R3, PR130, PR72

NCBI Gene: 5523 ENSG00000073711 UniProt: Q06190 OMIM: 604944

This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.36LOEUF

pLI 0.623

Z-score 5.00

OE 0.21 (0.13–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.04Z-score

OE missense 1.00 (0.94–1.07)

591 obs / 588.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.21 (0.13–0.36)

0≤0.351.4

Missense OE?1.00 (0.94–1.07)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 10 / 47.0Missense obs/exp: 591 / 588.3Syn Z: -0.15

Background carrier burden — how many people carry a rare variant somewhere in PPP2R3A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 33

1,520 rare PASS variants

Rare truncating (LoF)

1 in 460

208 rare PASS variants

Rare synonymous (reference)

1 in 83

551 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PPP2R3A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 44	1 in 1,200
South Asian	~43k	1 in 41	1 in 400
Remaining (unassigned)	~30k	1 in 28	1 in 1,300
European (Finnish)	~27k	1 in 140	1 in 2,400
Admixed American	~22k	1 in 37	1 in 450
African / African American	~21k	1 in 37	1 in 1,200
East Asian	~20k	1 in 39	1 in 2,200
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 42	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓