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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RRAD
RRAD, Ras related glycolysis inhibitor and calcium channel regulator
Chromosome 16 · 16q22.1
NCBI Gene: 6236Ensembl: ENSG00000166592.14HGNC: HGNC:10446UniProt: P55042
49PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcalcium channel regulator activityplasma membraneGTP bindingneoplasmcolorectal carcinomaoral squamous cell carcinomalung cancer
✦AI Summary

RRAD (Ras-related glycolysis inhibitor and calcium channel regulator) is a small GTPase that functions as a multifaceted regulator of calcium signaling and cellular metabolism. In cardiac tissue, RRAD negatively regulates L-type calcium channels (LTCC) by binding to channel β subunits and inhibiting channel open probability 1. β-adrenergic stimulation relieves this inhibition through protein kinase A-mediated phosphorylation of RRAD, enabling increased calcium influx and enhanced contractility 1. RRAD also inhibits cardiac hypertrophy via the CaMKII pathway, suggesting a protective role in heart disease 2. Notably, RRAD knockout in a dilated cardiomyopathy model paradoxically rescued systolic function and pathological remodeling while restoring calcium handling 3, revealing complex therapeutic potential for heart failure treatment. In cancer, RRAD exhibits context-dependent roles as both oncogene and tumor suppressor. RRAD downregulation promotes glucose metabolism and tumor progression in oral squamous cell carcinoma and papillary thyroid cancer through calcium-dependent activation of transcription factors regulating glucose transporters 4, 5. Conversely, RRAD functions as a tumor suppressor in ovarian cancer, where Ras-mediated epigenetic silencing promotes oncogenic glucose uptake 6. Additionally, RRAD regulates cell surface tension in senescent cells 7. These findings establish RRAD as a crucial regulator linking calcium homeostasis, metabolic adaptation, and disease progression across multiple tissue types.

Sources cited
1
RRAD (Rad) is a calcium channel inhibitor that is relieved of its inhibition by PKA phosphorylation during β-adrenergic stimulation, increasing LTCC channel open probability
PMID: 31969708
2
RRAD knockout in cardiomyocytes rescues dilated cardiomyopathy, restores calcium handling and sarcomere function, and reverses pathological gene expression signatures
PMID: 41032675
3
RRAD downregulation in oral squamous cell carcinoma enhances glucose uptake and tumor progression via calcium-dependent CAMKIV-CREB1 activation of GLUT3
PMID: 38811531
4
RRAD participates in a positive feedback loop with NEAT1_2 and EHF that facilitates aerobic glycolysis in papillary thyroid cancer
PMID: 37279586
5
Ras-mediated RRAD promoter hypermethylation silences RRAD expression in ovarian cancer, promoting glucose uptake and tumor formation; RRAD functions as a tumor suppressor
PMID: 24648519
6
RRAD regulates cell surface tension in senescent cells
PMID: 38760380
7
RRAD inhibits cardiac hypertrophy through inhibition of CAMKII phosphorylation and activation
PMID: 18056528
Disease Associationsⓘ20
neoplasmOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
hypertrophic cardiomyopathyOpen Targets
0.07Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.07Suggestive
Romano-Ward syndromeOpen Targets
0.07Suggestive
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.07Suggestive
Brugada syndromeOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
catecholaminergic polymorphic ventricular tachycardiaOpen Targets
0.06Suggestive
left ventricular noncompactionOpen Targets
0.06Suggestive
atrial fibrillationOpen Targets
0.06Suggestive
Familial short QT syndromeOpen Targets
0.06Suggestive
dilated cardiomyopathyOpen Targets
0.06Suggestive
familial atrial fibrillationOpen Targets
0.06Suggestive
dilated cardiomyopathy 1IOpen Targets
0.06Suggestive
Familial progressive cardiac conduction defectOpen Targets
0.06Suggestive
gastric cancerOpen Targets
0.05Suggestive
Atrial stand stillOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NUCB1Shared pathway100%NUCB2Shared pathway100%RAB42Shared pathway100%RALGPS2Shared pathway100%RASL12Shared pathway100%RASL10AShared pathway100%
Tissue Expression6 tissues
Heart
100%
Lung
30%
Ovary
9%
Bone Marrow
3%
Liver
2%
Brain
1%
Gene Interaction Network
Click a node to explore
RRADNUCB1NUCB2RAB42RALGPS2RASL12RASL10A
PROTEIN STRUCTURE
Preparing viewer…
PDB3Q72 · 1.66 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.73 [0.49–1.12]
RankingsWhere RRAD stands among ~20K protein-coding genes
  • #9,012of 20,598
    Most Researched49
  • #11,604of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedRRAD
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Friend or Foe: Regulation, Downstream Effectors of RRAD in Cancer.
PMID: 36979412
Biomolecules · 2023
1.00
2
The enhanced energy metabolism in the tumor margin mediated by RRAD promotes the progression of oral squamous cell carcinoma.
PMID: 38811531
Cell Death Dis · 2024
0.90
3
NEAT1_2/RRAD/EHF Positive Feedback Loop Facilitates Aerobic Glycolysis in Papillary Thyroid Cancer Cells.
PMID: 37279586
Endocrinology · 2023
0.80
4
Mechanism of adrenergic Ca
PMID: 31969708
Nature · 2020
0.70
5
High-throughput mechanical phenotyping and transcriptomics of single cells.
PMID: 38760380
Nat Commun · 2024
0.60