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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RCAN2
regulator of calcineurin 2
Chromosome 6 · 6p12.3
NCBI Gene: 10231Ensembl: ENSG00000172348.16HGNC: HGNC:3041UniProt: B2R612
27PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
calcium-dependent protein serine/threonine phosphatase regulator activitycalcium-mediated signalingnucleuscytoplasmAbnormality of the skeletal systemobesityamputationintestinal impaction
✦AI Summary

RCAN2 functions as an inhibitor of calcineurin-dependent signaling by binding to the catalytic domain of calcineurin A 1. While the UniProt annotation suggests a role in CNS development, current evidence primarily demonstrates its involvement in metabolic and oncologic processes. Metabolically, RCAN2 promotes food intake and weight gain through a leptin-independent hypothalamic mechanism 2. Rcan2 expression is enriched in ventromedial, dorsomedial, and paraventricular hypothalamic nuclei, and its genetic inactivation reduces food intake and ameliorates age- and diet-induced obesity in mice 2. In humans, serum RCAN2 concentrations correlate positively with BMI and overweight/obesity risk, with elevated levels also associated with metabolic abnormalities including dyslipidemia 3. RCAN2 similarly associates with non-alcoholic fatty liver disease (NAFLD) risk in humans and is upregulated in hepatic steatosis models 4. Oncologically, RCAN2 suppression enhances cancer stem cell properties in colorectal cancer by allowing calcineurin-dependent NFATC1 activation 5. In gliomas, RCAN2 dysregulation via circRNA-mediated mechanisms influences tumor growth through apoptotic pathways 6. Additionally, RCAN2 participates in p53 mutant pro-tumorigenic networks in pancreatic cancer 7. These findings position RCAN2 as a metabolic and oncologic regulator with potential diagnostic and therapeutic significance across multiple disease states.

Sources cited
1
Serum RCAN2 concentrations increase with BMI and are associated with overweight/obesity risk in humans
PMID: 35733783
2
Rcan2 inactivation in mice ameliorates obesity by reducing food intake; Rcan2 is expressed in hypothalamic nuclei regulating energy balance and acts through a leptin-independent pathway
PMID: 21298050
3
RCAN2 is regulated by circRNAs in glioma and influences tumor cell behavior through apoptotic mechanisms
PMID: 37918583
4
Elevated serum RCAN2 is associated with NAFLD risk in humans; RCAN2 is upregulated in hepatic steatosis models
PMID: 35370729
5
RCAN family members (including RCAN2) interact with and inhibit calcineurin
PMID: 21042787
6
RCAN2 suppression in colorectal cancer stem cells enhances stemness by allowing calcineurin-NFATC1 pathway activation
PMID: 37535148
7
RCAN2 participates in p53 mutant pro-tumorigenic networks in pancreatic cancer
PMID: 34348766
8
Rcan2 increases food intake and plays a role in age- and diet-induced obesity through leptin-independent mechanisms
PMID: 27604858
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.31Weak
obesityOpen Targets
0.29Weak
amputationOpen Targets
0.28Weak
intestinal impactionOpen Targets
0.28Weak
sialadenitisOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.26Weak
skin neoplasmOpen Targets
0.25Weak
color vision disorderOpen Targets
0.20Weak
cancerOpen Targets
0.09Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.04Suggestive
osteoarthritis, hipOpen Targets
0.04Suggestive
atypical teratoid rhabdoid tumorOpen Targets
0.04Suggestive
skin agingOpen Targets
0.04Suggestive
childhood supratentorial ependymomaOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
hair colorOpen Targets
0.03Suggestive
spondylolisthesisOpen Targets
0.03Suggestive
Barrett's esophagusOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPP3CAProtein interaction84%PPP3CBProtein interaction84%PPP3CCProtein interaction84%PPP3R1Protein interaction84%RCAN3Shared pathway50%MCTP2Shared pathway50%
Tissue Expression6 tissues
Heart
100%
Brain
23%
Ovary
4%
Lung
3%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
RCAN2PPP3CAPPP3CBPPP3CCPPP3R1RCAN3MCTP2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q14206
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.66LoF Tolerant
pLIⓘ
0.55Intermediate
Observed/Expected LoF0.38 [0.23–0.66]
RankingsWhere RCAN2 stands among ~20K protein-coding genes
  • #12,659of 20,598
    Most Researched27
  • #4,780of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedRCAN2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Association Between Circulating Regulator of Calcineurin 2 Concentrations With Overweight and Obesity.
PMID: 35733783
Front Endocrinol (Lausanne) · 2022
1.00
2
Inactivation of the Rcan2 gene in mice ameliorates the age- and diet-induced obesity by causing a reduction in food intake.
PMID: 21298050
PLoS One · 2011
0.90
3
CircIQGAP1 regulates RCAN1 and RCAN2 through the mechanism of ceRNA and promotes the growth of malignant glioma.
PMID: 37918583
Pharmacol Res · 2023
0.80
4
Elevated Serum Regulator of Calcineurin 2 is Associated With an Increased Risk of Non-Alcoholic Fatty Liver Disease.
PMID: 35370729
Front Pharmacol · 2022
0.70
5
Human RCAN3 gene expression and cell growth in endothelial cells.
PMID: 21042787
Int J Mol Med · 2010
0.60