PPP1R3A

Chr 7

protein phosphatase 1 regulatory subunit 3A

Also known as: GM, PP1G, PPP1R3

NCBI Gene: 5506ENSG00000154415UniProt: Q16821

The glycogen-associated form of protein phosphatase-1 (PP1) derived from skeletal muscle is a heterodimer composed of a 37-kD catalytic subunit and a 124-kD targeting and regulatory subunit. This gene encodes the regulatory subunit which binds to muscle glycogen with high affinity, thereby enhancing dephosphorylation of glycogen-bound substrates for PP1 such as glycogen synthase and glycogen phosphorylase kinase. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtType 2 diabetes mellitus
235
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PPP1R3A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 172 VUS of 235 total submissions
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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.01LOEUF
pLI 0.000
Z-score 1.52
OE 0.74 (0.55–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.30Z-score
OE missense 1.04 (0.97–1.11)
567 obs / 547.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.55–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.97–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 29 / 39.3Missense obs/exp: 567 / 547.3Syn Z: -1.10

ClinVar Variant Classifications

235 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS172
Likely Benign20
Benign16
Conflicting4
22
Pathogenic
1
Likely Pathogenic
172
VUS
20
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
1
166
5
0
172
Likely Benign
0
17
1
2
20
Benign
0
11
5
0
16
Conflicting
—4
Total1194342235

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PPP1R3A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A prevalent variant in PPP1R3A impairs glycogen synthesis and reduces muscle glycogen content in humans and mice.
Savage DB et al.·PLoS Med
2008
Peroxisome proliferator-activated receptor-gamma and insulin action: insights from human genetics.
Chatterjee VK·Horm Res
2003Review
Using gene and gene-set association tests to identify lethal prostate cancer genes.
Feng BJ et al.·Prostate Cancer Prostatic Dis
2025
Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is associated with type 2 diabetes.
Sánchez-Pozos K et al.·Mol Genet Genomics
2018
Phenotype of FOXP2 haploinsufficiency in a mother and son.
Rice GM et al.·Am J Med Genet A
2012Case report
Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the PPP1R3A locus.
Doney AS et al.·BMC Genet
2003
Obesity modifies the effects of the Asp905Tyr variant of PPP1R3A on risk of type 2 diabetes and insulin sensitivity.
Mammarella S et al.·Diabetes Obes Metab
2007
Molecular Differences between Screen-Detected and Interval Breast Cancers Are Largely Explained by PAM50 Subtypes.
Li J et al.·Clin Cancer Res
2017
Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach.
Dai L et al.·Front Med
2022
Digenic inheritance of severe insulin resistance in a human pedigree.
Savage DB et al.·Nat Genet
2002
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools