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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP1R12B
protein phosphatase 1 regulatory subunit 12B
Chromosome 1 · 1q32.1
NCBI Gene: 4660Ensembl: ENSG00000077157.23HGNC: HGNC:7619UniProt: A0A994J7P4
65PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingenzyme inhibitor activitymyosin phosphatase regulator activityneuron projection morphogenesispremature birthBenign Thyroid Gland NeoplasmacneCongenital lactic acidosis
✦AI Summary

PPP1R12B (protein phosphatase 1 regulatory subunit 12B) is a regulatory subunit of protein phosphatase 1 that modulates PP1 catalytic activity and substrate specificity 1. The protein regulates myosin phosphatase activity and augments calcium sensitivity of the contractile apparatus, with roles in muscle contraction regulation and cytoskeletal organization 2. PPP1R12B undergoes insulin-stimulated phosphorylation at multiple sites (particularly serine 29, serine 504, and serine 645/threonine 646), suggesting involvement in insulin signaling pathways 1. In cancer biology, PPP1R12B functions as a tumor suppressor. The PEAK1-PPP1R12B axis inhibits colorectal cancer growth and metastasis by suppressing the Grb2/PI3K/Akt signaling pathway 3, while microRNA-4463-mediated suppression of PPP1R12B promotes colon cancer cell proliferation and migration 4. PPP1R12B is downregulated in Wilms' tumor and associated with poor patient survival 5. Beyond cancer, PPP1R12B serves as a diagnostic biomarker for abdominal aortic aneurysm (AAA), where its downregulation may be mediated by N6-methyladenosine modification and correlates with AAA severity 6. Additionally, PPP1R12B is dysregulated in pelvic organ prolapse and diabetes mellitus, emerging as a key diagnostic gene in metabolic and connective tissue pathologies 78.

Sources cited
1
PPP1R12B binds PP1 catalytic subunits and undergoes insulin-stimulated phosphorylation at multiple sites including serine 29, serine 504, and serine 645/threonine 646
PMID: 22937917
2
PPP1R12B is a phosphatase involved in cytoskeletal regulation and is differentially expressed in response to mechanical stretch in periodontal ligament cells
PMID: 28681629
3
PEAK1-PPP1R12B axis suppresses colorectal cancer growth and metastasis by inhibiting Grb2/PI3K/Akt pathway activation
PMID: 30472186
4
MicroRNA-4463 suppresses PPP1R12B expression and promotes colorectal cancer cell proliferation and migration
PMID: 35064454
5
PPP1R12B is downregulated in abdominal aortic aneurysm samples, with expression changes potentially mediated by N6-methyladenosine modification, and serves as a diagnostic biomarker
PMID: 38070790
6
PPP1R12B is a hub gene in Wilms' tumor with downregulation correlating with poor overall survival
PMID: 34334530
7
PPP1R12B is identified as a focal adhesion signaling pathway hub gene in pelvic organ prolapse
PMID: 36176289
8
PPP1R12B is identified as a key diagnostic gene with altered expression in diabetes mellitus
PMID: 38682583
Disease Associationsⓘ20
premature birthOpen Targets
0.24Weak
Benign Thyroid Gland NeoplasmOpen Targets
0.21Weak
acneOpen Targets
0.15Weak
Congenital lactic acidosisOpen Targets
0.11Weak
ear malformationOpen Targets
0.09Suggestive
pernicious anemiaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
ankylosing spondylitisOpen Targets
0.03Suggestive
Takotsubo cardiomyopathyOpen Targets
0.03Suggestive
alcohol drinkingOpen Targets
0.03Suggestive
colorectal cancerOpen Targets
0.03Suggestive
open-angle glaucomaOpen Targets
0.03Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.02Suggestive
hypertensionOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
colorectal adenocarcinomaOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
breast carcinomaOpen Targets
0.01Suggestive
achalasia-alacrima syndromeOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPP1CBProtein interaction97%PPP1CCProtein interaction94%PPP1R14AProtein interaction71%MYH11Protein interaction70%MYLKProtein interaction70%PPP1R12AProtein interaction70%
Tissue Expression6 tissues
Heart
100%
Ovary
11%
Lung
8%
Brain
5%
Bone Marrow
4%
Liver
3%
Gene Interaction Network
Click a node to explore
PPP1R12BPPP1CBPPP1CCPPP1R14AMYH11MYLKPPP1R12A
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O60237
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.73LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.60 [0.49–0.73]
RankingsWhere PPP1R12B stands among ~20K protein-coding genes
  • #7,197of 20,598
    Most Researched65
  • #5,658of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedPPP1R12B
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Revealing PPP1R12B and COL1A1 as piRNA pathway genes contributing to abdominal aortic aneurysm through integrated analysis and experimental validation.
PMID: 38070790
Gene · 2024
1.00
2
Insulin-stimulated phosphorylation of protein phosphatase 1 regulatory subunit 12B revealed by HPLC-ESI-MS/MS.
PMID: 22937917
Proteome Sci · 2012
0.90
3
MicroRNA-4463 facilitates the development of colon cancer by suppression of the expression of PPP1R12B.
PMID: 35064454
Clin Transl Oncol · 2022
0.80
4
The PEAK1-PPP1R12B axis inhibits tumor growth and metastasis by regulating Grb2/PI3K/Akt signalling in colorectal cancer.
PMID: 30472186
Cancer Lett · 2019
0.70
5
Cyclic stretch-induced the cytoskeleton rearrangement and gene expression of cytoskeletal regulators in human periodontal ligament cells.
PMID: 28681629
Acta Odontol Scand · 2017
0.60