PPP1R1B Gene - Protein Phosphatase 1 Regulatory Inhibitor Subunit 1B
Key regulator of dopamine signaling and potential biomarker in cancer and neurological disorders
Gene Information Card
| Symbol | PPP1R1B |
|---|---|
| Full Name | Protein Phosphatase 1 Regulatory Inhibitor Subunit 1B |
| Gene Type | Protein coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 84152 ncbi.nlm.nih.gov/gene/84152 |
| Ensembl ID | ENSG00000131771 |
| UniProt ID | Q9UD71 |
| OMIM ID | 604399 |
| HGNC ID | 9282 |
| Aliases | DARPP-32, DARPP32, FLJ20940 |
Description
PPP1R1B encodes the protein DARPP-32 (dopamine- and cAMP-regulated neuronal phosphoprotein), a key regulator of protein phosphatase 1 (PP1) activity. It is highly expressed in the brain, particularly in striatal medium spiny neurons, where it integrates dopamine and glutamate signaling. Phosphorylation at Thr34 by PKA converts DARPP-32 into a potent PP1 inhibitor, while phosphorylation at Thr75 by Cdk5 converts it into a PKA inhibitor. The gene is also implicated in cancer, where aberrant expression and mutations contribute to tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered DARPP-32 phosphorylation disrupts dopamine signaling in striatum, contributing to cognitive and motor symptoms. | Association studies; postmortem brain analysis (PMID: 16936763) |
| Parkinson's disease | Dysregulation of DARPP-32 in striatal neurons affects PP1 activity and dopamine response, linked to motor deficits. | Animal models; human brain tissue (PMID: 12427854) |
| Huntington's disease | Reduced DARPP-32 expression in striatum correlates with neuronal dysfunction and chorea. | Gene expression studies; mouse models (PMID: 10973268) |
| Colorectal cancer | Overexpression of PPP1R1B promotes cell proliferation and metastasis via PP1 inhibition. | Immunohistochemistry; cell line assays (PMID: 21575863) |
| Gastric cancer | PPP1R1B amplification and overexpression associated with poor prognosis and chemoresistance. | Genomic profiling; clinical cohorts (PMID: 23361059) |
| Breast cancer | Elevated DARPP-32 levels linked to estrogen receptor signaling and tamoxifen resistance. | Cell line studies; patient samples (PMID: 21947069) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (caudate nucleus) | 78.5 | High |
| Brain (putamen) | 72.3 | High |
| Brain (nucleus accumbens) | 68.9 | High |
| Brain (frontal cortex) | 45.2 | Medium |
| Testis | 12.1 | Low |
| Kidney | 8.4 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 35.6 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
| MCF7 (breast cancer) | 18.4 | Moderate expression |
| HCT116 (colorectal cancer) | 42.7 | High expression |
| A549 (lung cancer) | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Alters PKA phosphorylation site; reduces PP1 inhibitory activity |
| c.223G>A (p.Ala75Thr) | Missense | <0.01% | Affects Cdk5 phosphorylation; potential gain-of-function |
| c.346_348del (p.Lys116del) | In-frame deletion | <0.01% | Unknown functional effect; reported in COSMIC |
| Amplification (17q12) | Copy number gain | ~5% in gastric cancer | Overexpression; associated with poor prognosis |
Mutation functional classification
Loss of Function (LOF)
Thr34Met mutation reduces PP1 inhibitory capacity, impairing dopamine signaling.
Gain of Function (GOF)
Ala75Thr may enhance PKA inhibition, leading to sustained cAMP signaling.
Dominant Negative (DN)
Not reported for PPP1R1B.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Dopamine-DARPP32 feedback in cAMP signaling (Reactome: R-HSA-389977)
• Glutamate signaling pathway (KEGG: hsa04724)
• Cocaine addiction (KEGG: hsa05030)
• Amphetamine addiction (KEGG: hsa05031)
• Alzheimer disease (KEGG: hsa05010)
Protein Summary
DARPP-32 is a 32 kDa phosphoprotein that acts as a molecular switch integrating dopaminergic and glutamatergic signaling in the brain. It is phosphorylated at multiple sites by PKA, Cdk5, and casein kinase, modulating its inhibitory activity toward PP1. In cancer, DARPP-32 overexpression promotes cell proliferation and metastasis, and its amplification is a biomarker in gastric and colorectal cancers. The protein is also implicated in neuropsychiatric and neurodegenerative disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPP1R1B Knockout HEK293 Cell Line | EDJ-KQ1806 | Human | 84152 | Details Get a Quote |
| PPP1R1B Knockout HeLa Cell Line | EDJ-KQ57539 | Human | 84152 | Details Get a Quote |
| PPP1R1B Knockout A-549 Cell Line | EDJ-KQ66037 | Human | 84152 | Details Get a Quote |
| PPP1R1B Knockout HCT 116 Cell Line | EDJ-KQ74461 | Human | 84152 | Details Get a Quote |
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