PPP2R1B

Chr 11

protein phosphatase 2 scaffold subunit Abeta

Also known as: PP2A-Abeta, PR65B

NCBI Gene: 5519 ENSG00000137713 UniProt: P30154

This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Mutations in this gene have been associated with some lung and colon cancers. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.000

Z-score 1.26

OE 0.77 (0.57–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.07Z-score

OE missense 0.84 (0.77–0.93)

311 obs / 369.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.57–1.06)

0≤0.351.4

Missense OE?0.84 (0.77–0.93)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 27 / 35.0Missense obs/exp: 311 / 369.0Syn Z: 0.59

Background carrier burden — how many people carry a rare variant somewhere in PPP2R1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

846 rare PASS variants

Rare truncating (LoF)

1 in 330

153 rare PASS variants

Rare synonymous (reference)

1 in 260

310 rare PASS variants

Rare missense and truncating variants are carried at similar rates in PPP2R1B; this gene does not show strong loss-of-function constraint by this measure. 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 130	1 in 380
South Asian	~43k	1 in 72	1 in 300
Remaining (unassigned)	~30k	1 in 60	1 in 300
European (Finnish)	~27k	1 in 150	1 in 460
Admixed American	~22k	1 in 57	1 in 260
African / African American	~21k	1 in 54	1 in 490
East Asian	~20k	1 in 53	1 in 840
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 62	1 in 410

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): 15 of 15 coding exons well covered in gnomAD exomes. Genomes: 14 of 15 (exon 1 below).? see exons ↓