PPP6R3

Chr 11

protein phosphatase 6 regulatory subunit 3

Also known as: C11orf23, PP6R3, SAP190, SAPL, SAPLa, SAPS3

NCBI Gene: 55291 ENSG00000110075 UniProt: Q5H9R7 OMIM: 610879

PPP6R3 encodes SAPS3, a regulatory subunit of protein phosphatase 6 that modulates the phosphatase's substrate specificity, recruits substrates, and determines its cellular localization. Mutations cause autosomal recessive early-onset immunodeficiency with recurrent infections, failure to thrive, and developmental delay. This reflects the protein's important role in maintaining immune self-tolerance.

OMIM ResearchSummary from RefSeq, UniProt

Protein phosphatase regulatory subunits, such as SAPS3, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS3 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).[supplied by OMIM, Nov 2010]

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

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.995

Z-score 5.57

OE 0.16 (0.09–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.54Z-score

OE missense 0.80 (0.73–0.87)

374 obs / 467.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.09–0.28)

0≤0.351.4

Missense OE?0.80 (0.73–0.87)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 50.9Missense obs/exp: 374 / 467.8Syn Z: -0.19

Background carrier burden — how many people carry a rare variant somewhere in PPP6R3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

970 rare PASS variants

Rare truncating (LoF)

1 in 2,400

96 rare PASS variants

Rare synonymous (reference)

1 in 110

398 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PPP6R3. 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 84	1 in 2,800
South Asian	~43k	1 in 64	1 in 1,800
Remaining (unassigned)	~30k	1 in 64	1 in 4,900
European (Finnish)	~27k	1 in 200	1 in 2,600
Admixed American	~22k	1 in 77	1 in 1,200
African / African American	~21k	1 in 92	1 in 2,000
East Asian	~20k	1 in 73	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 740	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 88	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): 21 of 22 coding exons well covered in gnomAD exomes; exon 15 marginal. Genomes: all 22.? see exons ↓