PPP1R3A
protein-codingprotein phosphatase 1 regulatory subunit 3A, the group of Protein phosphatase 1 regulatory subunits
Gene summary
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]
- PPP1R3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~199.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007455
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: Unknown
Disease ID:MONDO:0007455
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0005148
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Severe digenic insulin resistance has been reported as resulting from digenic variants in PPP1R3A and PPARG
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPP1R3A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002711.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 6 | ||||
| missense | 168 | 23 | 6 | 197 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 169 | 29 | 6 | 204 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002702.2 | 4 | MANE Select | |
| Ensembl | ENSP00000284601.3 | 4 | MANE Select | |
| Ensembl | ENSP00000284602.1 | 2 | Standard | |
| Ensembl | ENSP00000401278.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Insulin resistance - Homo sapiens (human)
- Insulin signaling pathway - Homo sapiens (human)
- Insulin Signaling
- Insulin-mediated glucose transport
Biological Process
- glycogen metabolic process
Cellular Component
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000284601
- Coding exons
- 4
- Length
- 199144
- Individuals with no LoFs
- 125018
- Homozygous LoFs
- 5
- Heterozygous LoFs
- 705
- Defined
- 125728
- p
- 0.00283
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.300 | 567 | 547 | 1.04 | 0.0000269 | 7356 |
| Missense (PolyPhen) | 101 | 105.23 | 0.95979 | 1545 | ||
| Synonymous | -1.10 | 219 | 199 | 1.10 | 0.0000104 | 2100 |
| Loss of Function | 1.52 | 29 | 39.3 | 0.738 | 0.00000214 | 571 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0021 | 0.0021 | notable |
| Latino/Admixed American | 0.00084 | 0.00084 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0.0014 | 0.0014 | notable |
| European (Non-Finnish) | 0.0049 | 0.0048 | notable |
| South Asian | 0.0014 | 0.0014 | notable |
| Other | 0.0021 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:7926294}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.184
Intolerance Scores
- LoFtool
- 0.967
- RVIS EVS
- 2.67
- RVIS percentile EVS
- 98.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.477
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | High | Medium | High |