PPP1R3A Gene - Protein Phosphatase 1 Regulatory Subunit 3A
Key regulator of glycogen metabolism and insulin signaling
Gene Information Card
| Symbol | PPP1R3A |
|---|---|
| Full Name | Protein Phosphatase 1 Regulatory Subunit 3A |
| Gene Type | Protein coding |
| Chromosomal Location | 7q31.1 |
| NCBI Gene ID | 5506 ncbi.nlm.nih.gov/gene/5506 |
| Ensembl ID | ENSG00000105971 |
| UniProt ID | Q16821 |
| OMIM ID | 600917 |
| HGNC ID | 9291 |
| Aliases | PP1G, PPP1R3, GM, RGL, PP1 subunit G, glycogen-associated regulatory subunit of PP1 |
Description
PPP1R3A encodes the glycogen-associated regulatory subunit of protein phosphatase 1 (PP1). This subunit targets PP1 to glycogen particles, where it dephosphorylates glycogen synthase and phosphorylase, thereby promoting glycogen synthesis and inhibiting glycogenolysis. It plays a critical role in insulin-stimulated glucose storage in muscle and liver. Variants in PPP1R3A have been associated with altered glycogen metabolism and insulin resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 diabetes | Impaired insulin-stimulated glycogen synthesis due to reduced PP1 targeting to glycogen | PMID: 10625657; ClinVar |
| Glycogen storage disease type XV (suspected) | Loss of function leads to abnormal glycogen accumulation | OMIM #600917 |
| Insulin resistance | Defective PP1 regulatory subunit reduces glycogen synthase activation | PMID: 10949030 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 45.2 | High |
| Heart | 38.1 | High |
| Liver | 12.5 | Medium |
| Adipose tissue | 8.3 | Low |
| Brain | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 22.4 | Hepatocyte model |
| C2C12 | 58.7 | Myoblast model |
| HEK293 | 6.2 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1987C>T (p.Arg663Cys) | Missense | 0.02% | Reduced glycogen binding affinity |
| c.883G>A (p.Asp295Asn) | Missense | 0.01% | Impaired PP1 interaction |
| c.1342_1343del (p.Leu448fs) | Frameshift | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the PP1-binding domain lead to loss of glycogen-targeting function.
Gain of Function (GOF)
No gain-of-function mutations reported in PPP1R3A.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg663Cys) may act dominant-negative by competing with wild-type subunit for PP1 binding without proper glycogen targeting.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Insulin signaling pathway (KEGG: hsa04910)
• Glycogen metabolism (Reactome: R-HSA-70221)
• PP1 regulatory network (Reactome: R-HSA-163615)
Protein Summary
PPP1R3A is a 1109-amino acid protein that functions as a regulatory subunit of protein phosphatase 1 (PP1). It contains a glycogen-binding domain (GBD) that targets PP1 to glycogen particles, and a PP1-binding motif (RVxF). The protein is highly expressed in skeletal muscle and heart, where it facilitates insulin-stimulated glycogen synthesis. Mutations in PPP1R3A can impair glycogen targeting and contribute to insulin resistance and type 2 diabetes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPP1R3A Knockout HEK293 Cell Line | EDJ-KQ5518 | Human | 5506 | Details Get a Quote |
| PPP1R3A Knockout HeLa Cell Line | EDJ-KQ54194 | Human | 5506 | Details Get a Quote |
| PPP1R3A Knockout A-549 Cell Line | EDJ-KQ62688 | Human | 5506 | Details Get a Quote |
| PPP1R3A Knockout HCT 116 Cell Line | EDJ-KQ71156 | Human | 5506 | Details Get a Quote |
