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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RUVBL2
RuvB like AAA ATPase 2
Chromosome 19 · 19q13.33
NCBI Gene: 10856Ensembl: ENSG00000183207.16HGNC: HGNC:10475UniProt: B3KNL2
452PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHighly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
telomerase RNA localization to Cajal bodyRNA polymerase II cis-regulatory region sequence-specific DNA bindingRNA polymerase II core promoter sequence-specific DNA bindingprotein bindingneurodegenerative diseasehepatocellular carcinomaneoplasmcancer
✦AI Summary

RUVBL2 is a highly conserved AAA+ ATPase functioning as a versatile scaffold in multiple cellular processes 1. It possesses single-stranded DNA-stimulated ATPase and 5' to 3' DNA helicase activities, with hexamerization critical for ATP hydrolysis. RUVBL2 forms a hetero-hexameric complex with RUVBL1 that participates in chr19 remodeling, including the NuA4 histone acetyltransferase complex and INO80 complex, facilitating transcriptional activation through histone acetylation and nucleosome remodeling 2. Notably, RUVBL2 functions as a conserved eukaryotic circadian clock component with remarkably slow ATPase activity (~13 ATP molecules/day), regulating circadian phase through interaction with core clock proteins like BMAL1 34. RUVBL2 plays essential roles in MYC-driven oncogenic transformation and is involved in nonsense-mediated mRNA decay and assembly of large macromolecular complexes including RNA polymerases and mTOR complexes 15. In colorectal cancer, RUVBL1/2 overexpression correlates with poor prognosis and drives m6A-dependent oncogenic translation through interaction with YTHDF1 6. These findings position RUVBL2 as a druggable target in cancer therapeutics and a fundamental component of eukaryotic circadian regulation.

Sources cited
1
RUVBL1-RUVBL2 form a hetero-hexameric complex participating in chromatin remodeling, Fanconi Anemia, NMD, and assembly of RNA polymerases, snoRNP, and mTOR complexes
PMID: 33129013
2
RUVBL2 regulates circadian phase by interacting with clock proteins on chromatin; cordycepin perturbation causes 12-hour phase shifts and disassembles RUVBL2-BMAL1 interaction
PMID: 32376767
3
RUVBL2 is a conserved P-loop NTPase with remarkably slow ATPase activity (~13 ATP/day) that influences circadian period through interaction with core clock proteins across fungi, plants, and animals
PMID: 40140583
4
In the human TIP60 complex, RUVBL1-RUVBL2 hexamer serves as a rigid core for assembly of EP400 ATPase and other motor module components
PMID: 39154037
5
RUVBL1/2 are essential for MYC to establish oncogenic and immunoevasive gene expression in pancreatic cancer; degradation of RUVBL1 causes tumor regression and immune cell infiltration
PMID: 38821858
6
RUVBL1/2 are overexpressed in colorectal cancer and drive m6A-dependent oncogenic translation through positive feedforward circuit with YTHDF1; RUVBL1/2 inhibition is a therapeutic strategy
PMID: 38900944
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.27Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
isolated agammaglobulinemiaOpen Targets
0.06Suggestive
Alymphoid cystic thymic dysgenesisOpen Targets
0.06Suggestive
goutOpen Targets
0.06Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.06Suggestive
autoimmune diseaseOpen Targets
0.06Suggestive
T-B+ severe combined immunodeficiency due to JAK3 deficiencyOpen Targets
0.06Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.06Suggestive
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.05Suggestive
immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopeniasOpen Targets
0.05Suggestive
immunodeficiency 18Open Targets
0.05Suggestive
primary immunodeficiency syndrome due to p14 deficiencyOpen Targets
0.05Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.05Suggestive
immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemiaOpen Targets
0.05Suggestive
Hodgkins lymphomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ZNHIT2Protein interaction100%CTNNB1Protein interaction100%PFDN2Protein interaction100%SPAG1Protein interaction100%UXTProtein interaction100%URI1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
98%
Liver
84%
Heart
75%
Lung
65%
Ovary
63%
Gene Interaction Network
Click a node to explore
RUVBL2ZNHIT2CTNNB1PFDN2SPAG1UXTURI1
PROTEIN STRUCTURE
Preparing viewer…
PDB8QR1 · 2.40 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.25Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.08–0.25]
RankingsWhere RUVBL2 stands among ~20K protein-coding genes
  • #610of 20,598
    Most Researched452 · top 5%
  • #749of 17,882
    Most Constrained (LOEUF)0.25 · top 5%
Genes detectedRUVBL2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
RUVBL1-RUVBL2 AAA-ATPase: a versatile scaffold for multiple complexes and functions.
PMID: 33129013
Curr Opin Struct Biol · 2021
1.00
2
Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals.
PMID: 32376767
Sci Transl Med · 2020
0.90
3
The P-loop NTPase RUVBL2 is a conserved clock component across eukaryotes.
PMID: 40140583
Nature · 2025
0.80
4
RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD.
PMID: 39638345
Life Sci Alliance · 2025
0.76
5
Structure of the human TIP60 complex.
PMID: 39154037
Nat Commun · 2024
0.70