RUVBL1

Summary

RUVBL1 (RuvB like AAA ATPase 1, HGNC:10474) is a protein-coding gene on chromosome 3q21.3, encoding RuvB-like 1 (Q9Y265). Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3’ to 5’) activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a protein that has both DNA-dependent ATPase and DNA helicase activities and belongs to the ATPases associated with diverse cellular activities (AAA+) protein family. The encoded protein associates with several multisubunit transcriptional complexes and with protein complexes involved in both ATP-dependent remodeling and histone modification. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 8607 — RefSeq curated summary.

At a glance

• GWAS associations: 84
• Clinical variants (ClinVar): 181 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_003707

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10474
Approved symbol	RUVBL1
Name	RuvB like AAA ATPase 1
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	TIP49, NMP238, RVB1, TIP49a, Pontin52, ECP54, TIH1, Rvb1, INO80H
Ensembl gene	ENSG00000175792
Ensembl biotype	protein_coding
OMIM	603449
Entrez	8607

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000322623, ENST00000464873, ENST00000472125, ENST00000478243, ENST00000478892, ENST00000480616, ENST00000582176, ENST00000585057, ENST00000881248, ENST00000881249, ENST00000881250, ENST00000881251, ENST00000881252, ENST00000881253, ENST00000931761, ENST00000931762, ENST00000931763, ENST00000931764

RefSeq mRNA: 3 — MANE Select: NM_003707 NM_001319084, NM_001319086, NM_003707

CCDS: CCDS3047, CCDS82833

Canonical transcript exons

ENST00000322623 — 11 exons

Exon	Start	End
ENSE00001224692	128082483	128082574
ENSE00001224702	128087706	128087808
ENSE00001224713	128097300	128097498
ENSE00001224731	128100595	128100744
ENSE00001224739	128101559	128101648
ENSE00001224746	128104773	128104924
ENSE00001224784	128098882	128098945
ENSE00001224791	128112888	128113020
ENSE00001775556	128080810	128081409
ENSE00001792355	128123584	128123812
ENSE00003492006	128119328	128119414

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.2479 / max 864.2320, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44421	50.0894	1805
44423	0.1585	56

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.42	gold quality
ventricular zone	UBERON:0003053	94.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.56	gold quality
cortical plate	UBERON:0005343	93.21	gold quality
fallopian tube	UBERON:0003889	92.87	gold quality
ganglionic eminence	UBERON:0004023	92.76	gold quality
islet of Langerhans	UBERON:0000006	92.14	gold quality
stromal cell of endometrium	CL:0002255	91.72	gold quality
right testis	UBERON:0004534	91.54	gold quality
placenta	UBERON:0001987	91.07	gold quality
left testis	UBERON:0004533	91.07	gold quality
testis	UBERON:0000473	90.90	gold quality
lymph node	UBERON:0000029	90.27	gold quality
mucosa of transverse colon	UBERON:0004991	90.06	gold quality
heart left ventricle	UBERON:0002084	90.00	gold quality
right atrium auricular region	UBERON:0006631	89.75	gold quality
smooth muscle tissue	UBERON:0001135	89.62	gold quality
left uterine tube	UBERON:0001303	89.61	gold quality
heart	UBERON:0000948	89.59	gold quality
esophagus mucosa	UBERON:0002469	89.52	gold quality
vermiform appendix	UBERON:0001154	89.34	gold quality
pancreas	UBERON:0001264	89.34	gold quality
myometrium	UBERON:0001296	89.13	gold quality
spleen	UBERON:0002106	88.96	gold quality
body of uterus	UBERON:0009853	88.92	gold quality
adult mammalian kidney	UBERON:0000082	88.80	gold quality
right adrenal gland	UBERON:0001233	88.79	gold quality
pituitary gland	UBERON:0000007	88.73	gold quality
cortex of kidney	UBERON:0001225	88.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TP53	Repression

Upstream regulators (CollecTRI, top): EHF

miRNA regulators (miRDB)

30 targeting RUVBL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-1285-5P	98.01	68.71	779
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-25-5P	87.02	64.95	84

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Pontin52/TIP49a promotes COX-2 expression in tissue culture and is overexpressed in colon cancer tissue, co-localizing with COX-2 expression in transformed tissue, relative to paired normal tissue (PMID:14675489)
• TIP49 is an important cofactor in beta-catenin/TCF gene regulation in normal and neoplastic cells, likely functioning in chromatin remodeling. (PMID:14695187)
• similar to the yeast INO80 complex, the hINO80 complex of Tip49a and Tip49b exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PMID:16230350)
• structure of the RuvBL1.ADP complex, combined with our biochemical results, suggest that although RuvBL1 has all the structural characteristics of a molecular motor, even of an ATP-driven helicase (PMID:17060327)
• The results point to biochemical differences between TIP48 and TIP49, which may explain the structural differences between the two hexameric rings and could be significant for specialised functions that the proteins perform individually. (PMID:17157868)
• pontin is a component of chromatin-remodeling complexes that is SUMO-modified, which has a role in transcriptional regulation of pontin on androgen-receptor target genes in prostate cancer cells (PMID:18087039)
• Rvb1 is critical for the dephosphorylation of phospho-H2AX due to the role of Rvb1 in maintaining the histone acetyltransferase activity of Tip60/NuA4 (PMID:18285460)
• Study identifies the ATPases pontin and reptin as telomerase components through affinity purification of TERT from human cells. (PMID:18358808)
• Pontin has a mitosis-specific function in regulating microtubule assembly (PMID:18463163)
• Pontin was found to associate with RNA polymerase I and to interact in a complex with c-Myc with rDNA sequences indicating that Pontin is involved in the c-Myc-dependent regulation of rRNA synthesis. (PMID:18548265)
• Crystal structure has been solved and the solutions obtained show that the RuvBL1-RuvBL2 complex forms a dodecamer. (PMID:18765919)
• The results suggest that as a constituent of chromatin modification complexes TIP49 may facilitate the access of the repair machinery to the sites of DNA damage. (PMID:18834951)
• Phorbol ester enhances KAI1 transcription by recruiting Tip60/Pontin complexes (PMID:19048121)
• Is part of an RNA polymerase II-associated complex with possible chaperone activity. (PMID:19450687)
• RVB1 and RVB2 function within multiple protein complexes is reviewed. (PMID:19524533)
• snoRNP assembly factor NUFIP can regulate the interactions between TIP48 and TIP49 and the core box C/D proteins. (PMID:19620283)
• Reptin and Pontin protein levels are strictly controlled by a posttranslational mechanism involving proteasomal degradation of newly synthesized proteins. (PMID:19877184)
• S100A9 and NMP238 expression is associated with concurrent chemoradiotherapy sensitivity in cervical carcinoma. (PMID:20130364)
• RUVBL1 and RUVBL2 control the abundance of Phosphatidylinositol 3-kinase (PI3K)-related protein kinases (PIKKs), and stimulate the formation of PIKK-containing molecular complexes, such as those involved in nonsense-mediated mRNA decay. (PMID:20371770)
• Several experimental approaches were used to investigate the molecular architecture of the RuvBL1-RuvBL2 complex and the role of the ATPase-insert domain (domain II) for its assembly and stability. (PMID:20412048)
• These results indicate that EHF-mediated RUVBL1 expression allows colon tumour cells to avoid p53-mediated apoptosis. (PMID:21617703)
• Pontin is methylated by G9a/GLP methyltransferases in hypoxic condition and potentiates HIF-1alpha-mediated activation by increasing the recruitment of p300 coactivator to a subset of HIF-1alpha target promoters. (PMID:21825155)
• DNA unwinding of the human RuvBL proteins can be auto-inhibited by domain II, which is not present in the homologous bacterial helicase RuvB. (PMID:21933716)
• Pontin-positivity seems to be a negative predictor for response to adjuvant therapy in colorectal cancer patients and may help to identify patients with adverse outcome in advanced tumor stages. (PMID:22895545)
• First insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes. (PMID:22923768)
• Two coexisting conformations, compact and stretched, are revealed by analysis of cryo-electron microscopy structures of the RuvBL1-RuvBL2 complex. (PMID:23002137)
• Data indicate that the RVB1/2 chromatin-remodeling complex is required for efficient Pol II recruitment and initiation at IFN-alpha-stimulated genes (ISGs) promoters and is recruited through interaction with the STAT2 transactivation domain. (PMID:23878400)
• Anti-RuvBL1/2 antibody is a novel systemic scleroderma-related autoantibody associated with a unique combination of clinical features, including myositis overlap and diffuse cutaneous involvement. (PMID:24023044)
• Upregulation of PONTIN by AML1-ETO participate in the oncogenic growth of t(8;21) leukemia cells. (PMID:24342949)
• Results showed RUVBL1 promoting concentration of G-actin subunits and polymerization of actin filaments via its direct binding to F-actin in cell protrusions and results in increased invasive properties of pancreatic ductal adenocarcinoma cells. (PMID:24728183)
• these findings suggest that YY1-RuvBL1-RuvBL2 complexes could contribute to functions beyond transcription, and we show that YY1 and the ATPase activity of RuvBL2 are required for RAD51 foci formation during homologous recombination. (PMID:24990942)
• Reptin and Pontin oligomerization and activity are modulated through histone H3 N-terminal tail interaction. (PMID:25336637)
• The results suggests that a potential mechanism for the role of RuvBL1-RuvBL2 in maintaining genome integrity is through controlling the cellular abundance of Fanconi anaemia core complex. (PMID:25428364)
• Study showed that pontin is up-regulated in renal cell carcinoma (RCC) and high cytoplasmic pontin expression was associated with poor survival of RCC patients. (PMID:25751257)
• Results highlight an important role and mechanism for Pontin, a new mutp53 partner, in promoting mutp53 GOF in tumorigenesis. (PMID:25857266)
• data thus demonstrate that RUVBL1 is essential for efficient mitosis and proliferation. (PMID:26201077)
• RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils. (PMID:26303906)
• The interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. (PMID:26711270)
• by means of molecular docking approaches we first modeled the structures of hetero-hexameric TIP49 ( TIP49a and TIP49b )complexes with short ds-DNA fragments (20 base pairs with different GC content) within the central channel of hexameric ring (PMID:26863765)
• association of c-FLIPL and TIP49 provided an additional mechanism involved in c-FLIPL-mediated functions, including Wnt activation (PMID:28028178)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ruvbl1	ENSDARG00000002591
mus_musculus	Ruvbl1	ENSMUSG00000030079
rattus_norvegicus	Ruvbl1	ENSRNOG00000013195
rattus_norvegicus	Ruvbl1-ps1	ENSRNOG00000059655
drosophila_melanogaster	pont	FBGN0040078

Paralogs (1): RUVBL2 (ENSG00000183207)

Protein

Protein identifiers

RuvB-like 1 — Q9Y265 (reviewed: Q9Y265)

Alternative names: 49 kDa TATA box-binding protein-interacting protein, 54 kDa erythrocyte cytosolic protein, INO80 complex subunit H, Nuclear matrix protein 238, Pontin 52, TIP49a, TIP60-associated protein 54-alpha

All UniProt accessions (6): Q9Y265, A0A384MTR5, E7ETR0, H7C4G5, H7C4I3, J3QLR1

UniProt curated annotations — full annotation on UniProt →

Function. Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3’ to 5’) activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity. Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding. Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. Essential for cell proliferation. May be able to bind plasminogen at cell surface and enhance plasminogen activation.

Subunit / interactions. Forms homohexameric rings. Can form a dodecamer with RUVBL2 made of two stacked hexameric rings; however, even though RUVBL1 and RUVBL2 are present in equimolar ratio, the oligomeric status of each hexamer is not known. Oligomerization may regulate binding to nucleic acids and conversely, binding to nucleic acids may affect the dodecameric assembly. Interaction of the complex with DHX34 results in conformational changes of the N-terminus of the RUVBL2 subunits, resulting in loss of nucleotide binding ability and ATP hydrolysis of the complex. Interacts with the transcriptional activation domain of MYC. Component of the RNA polymerase II holoenzyme complex. May also act to bridge the LEF1/TCF1-CTNNB1 complex and TBP. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. RUVBL1 interacts with EP400. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Component of the BAF53 complex, at least composed of ACTL6A/BAF53A, RUVBL1/TIP49, SMARCA2/BRM, and TRRAP/PAF400. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Associates with alpha and gamma tubulins, particularly during metaphase and early anaphase. Interacts with NPAT. Component of the chromatin-remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Interacts with IGHMBP2. Interacts with OFD1. Interacts with HINT1. Component of a complex with USP49 and PSMC5. Component of a SWR1-like complex. Component of the R2TP complex composed at least of RUVBL1, RUVBL2, RPAP3 and PIHD1. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with PIH1D1. Interacts with ITFG1. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation. The RUVBL1/RUVBL2 complex interacts with ZNHIT1 (via HIT-type zinc finger), ZNHIT3 (via HIT-type zinc finger), ZNHIT6 (via HIT-type zinc finger) and DDX59/ZNHIT5 (via HIT-type zinc finger) in the presence of ADP. Interacts with NOPCHAP1; the interaction is direct and disrupted upon ATP binding. Interacts with SMG1. Interacts with NOP2, NOP56 and NUFIP1. (Microbial infection) Interacts with Mumps L polymerase; this interaction regulates the viral transcription.

Subcellular location. Nucleus matrix. Nucleus. Nucleoplasm. Cytoplasm. Membrane. Cytoskeleton. Microtubule organizing center. Centrosome. Dynein axonemal particle.

Tissue specificity. Ubiquitously expressed with high expression in heart, skeletal muscle and testis.

Domain organisation. Binding to MYC is dependent on a Myc domain essential for oncogenic activity.

Miscellaneous. High level of autoantibodies against RUVBL1 are detected in sera of patients with autoimmune diseases such as polymyositis/dermatomyosistis and autoimmune hepatitis.

Similarity. Belongs to the RuvB family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y265-1	1	yes
Q9Y265-2	2

RefSeq proteins (3): NP_001306013, NP_001306015, NP_003698* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR010339	TIP49_P-loop	Domain
IPR027238	RuvB-like	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041048	RuvB-like_C	Domain
IPR042487	RuvBL1/2_DNA/RNA_bd_dom	Homologous_superfamily

Pfam: PF06068, PF17856

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (64 total): strand 25, helix 19, sequence conflict 4, turn 4, cross-link 4, mutagenesis site 3, splice variant 2, chain 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2C9O	X-RAY DIFFRACTION	2.2
8QR1	ELECTRON MICROSCOPY	2.4
9EMA	ELECTRON MICROSCOPY	2.4
6K0R	X-RAY DIFFRACTION	2.5
9C57	ELECTRON MICROSCOPY	2.75
2XSZ	X-RAY DIFFRACTION	3
9CAE	ELECTRON MICROSCOPY	3.07
7ZI4	ELECTRON MICROSCOPY	3.2
8X15	ELECTRON MICROSCOPY	3.2
8X19	ELECTRON MICROSCOPY	3.2
8X1C	ELECTRON MICROSCOPY	3.2
8XVT	ELECTRON MICROSCOPY	3.2
9EMC	ELECTRON MICROSCOPY	3.26
9CA7	ELECTRON MICROSCOPY	3.35
9GE5	ELECTRON MICROSCOPY	3.35
7OLE	ELECTRON MICROSCOPY	3.41
9CAC	ELECTRON MICROSCOPY	3.43
9GCG	ELECTRON MICROSCOPY	3.43
9GEV	ELECTRON MICROSCOPY	3.47
9HPO	ELECTRON MICROSCOPY	3.5
9GFB	ELECTRON MICROSCOPY	3.55
9CA9	ELECTRON MICROSCOPY	3.56
9HB4	ELECTRON MICROSCOPY	3.56
6FO1	ELECTRON MICROSCOPY	3.57
6QI8	ELECTRON MICROSCOPY	3.75
9CA8	ELECTRON MICROSCOPY	3.92
9CAB	ELECTRON MICROSCOPY	3.94
6IGM	ELECTRON MICROSCOPY	4
9CAA	ELECTRON MICROSCOPY	4.04
5OAF	ELECTRON MICROSCOPY	4.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y265-F1	87.55	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 70–77

Post-translational modifications (5): 453, 2, 225, 225, 445

Mutagenesis-validated functional residues (3):

Position	Phenotype
302	abolishes atpase activity; inhibition of myc- and ctnnb1-mediated transformation.
303	reduces atpase activity. decreases interaction with nopchap1. no effect on formation of ruvbl1-ruvbl2 heteromeric comple
76	no effect on interaction with nopchap1.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3214847	HATs acetylate histones
R-HSA-5689603	UCH proteinases
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-157579	Telomere Maintenance
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-180786	Extension of Telomeres
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-392499	Metabolism of proteins
R-HSA-4839726	Chromatin organization
R-HSA-5688426	Deubiquitination
R-HSA-5696398	Nucleotide Excision Repair
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-597592	Post-translational protein modification
R-HSA-73886	Chromosome Maintenance
R-HSA-73894	DNA Repair
R-HSA-774815	Nucleosome assembly

MSigDB gene sets: 382 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, MATTIOLI_MGUS_VS_PCL, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR, GOCC_MICROTUBULE_ORGANIZING_CENTER, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE

GO Biological Process (26): box C/D snoRNP assembly (GO:0000492), telomere maintenance (GO:0000723), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), regulation of chromosome organization (GO:0033044), regulation of apoptotic process (GO:0042981), positive regulation of DNA repair (GO:0045739), positive regulation of DNA-templated transcription (GO:0045893), regulation of embryonic development (GO:0045995), protein stabilization (GO:0050821), cell division (GO:0051301), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), positive regulation of canonical Wnt signaling pathway (GO:0090263), telomerase RNA localization to Cajal body (GO:0090671), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of double-strand break repair (GO:2000779), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (14): TFIID-class transcription factor complex binding (GO:0001094), DNA helicase activity (GO:0003678), transcription coactivator activity (GO:0003713), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), TBP-class protein binding (GO:0017025), ADP binding (GO:0043531), cadherin binding (GO:0045296), ATPase binding (GO:0051117), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), hydrolase activity (GO:0016787)

GO Cellular Component (21): nucleosome (GO:0000786), Swr1 complex (GO:0000812), nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), Ino80 complex (GO:0031011), NuA4 histone acetyltransferase complex (GO:0035267), ciliary basal body (GO:0036064), extracellular exosome (GO:0070062), MLL1 complex (GO:0071339), R2TP complex (GO:0097255), protein folding chaperone complex (GO:0101031), dynein axonemal particle (GO:0120293), RPAP3/R2TP/prefoldin-like complex (GO:1990062), ribonucleoprotein complex (GO:1990904), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Deubiquitination	2
Extension of Telomeres	1
TCF dependent signaling in response to WNT	1
Chromatin modifying enzymes	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Nucleosome assembly	1
Chromosome Maintenance	1
Telomere Maintenance	1
Signal Transduction	1
Signaling by WNT	1
Chromatin organization	1
Post-translational protein modification	1
DNA Repair	1
Nucleotide Excision Repair	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
DNA metabolic process	3
regulation of DNA metabolic process	3
ATP-dependent activity	3
protein-containing complex	3
DNA repair	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
adenyl ribonucleotide binding	2
nuclear chromosome	2
INO80-type complex	2
nuclear lumen	2
microtubule organizing center	2
cytoplasm	2
small nucleolar ribonucleoprotein complex assembly	1
telomere organization	1
DNA replication	1
DNA damage response	1
regulation of cellular response to stress	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
developmental process involved in reproduction	1
male gamete generation	1
regulation of organelle organization	1
chromosome organization	1
apoptotic process	1
regulation of programmed cell death	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
positive regulation of RNA biosynthetic process	1
embryo development	1
regulation of multicellular organismal development	1
regulation of protein stability	1
cellular process	1
cell cycle	1
regulation of cellular process	1
DNA strand elongation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

487 interactions, top by confidence:

A	B	Type	Score
RUVBL2	RUVBL1	psi-mi:“MI:0915”(physical association)	0.970
RUVBL1	RUVBL2	psi-mi:“MI:0915”(physical association)	0.970
INO80E	YY1	psi-mi:“MI:0914”(association)	0.900
RUVBL1	KAT5	psi-mi:“MI:0915”(physical association)	0.890
PIH1D1	RUVBL2	psi-mi:“MI:0914”(association)	0.860
ECD	PRPF8	psi-mi:“MI:0914”(association)	0.820
RUVBL1	DKC1	psi-mi:“MI:0914”(association)	0.820
RUVBL1	DKC1	psi-mi:“MI:0407”(direct interaction)	0.820
DKC1	RUVBL1	psi-mi:“MI:0915”(physical association)	0.820
ACTR6	ZNHIT1	psi-mi:“MI:0914”(association)	0.820
RUVBL2	DKC1	psi-mi:“MI:0914”(association)	0.810
ZNHIT2	RUVBL1	psi-mi:“MI:0915”(physical association)	0.800
DKC1	TERT	psi-mi:“MI:0914”(association)	0.750
PIH1D1	ECD	psi-mi:“MI:0914”(association)	0.740
MBTD1	YEATS4	psi-mi:“MI:0914”(association)	0.730

BioGRID (1062): RUVBL1 (Affinity Capture-MS), RUVBL2 (Two-hybrid), RUVBL1 (Affinity Capture-RNA), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Reconstituted Complex), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS)

ESM2 similar proteins: A0B738, A2SQD1, A3CUA0, A4FWP8, A5N842, A5UJ82, A5UJB8, A5UKA4, A6UPT0, A6UV02, A6VGM3, A7I6K3, A8GN00, A9AA28, A9BJ54, B3PN08, B6YSY6, B8GFL8, C5A1K9, O59362, P33561, P60123, Q0W793, Q12V67, Q2FLB2, Q2NEM0, Q44772, Q469M4, Q46DW1, Q50318, Q58603, Q5JH14, Q68X52, Q6BI60, Q6FU78, Q6L1F0, Q6LXR3, Q7NBZ4, Q8EUL1, Q8PXC6

Diamond homologs: O17607, O94692, P0CR26, P0CR27, P0CR28, P0CR29, P60122, P60123, P83571, Q03940, Q0IFL2, Q12464, Q16TA2, Q29AK9, Q29DI0, Q2TBU9, Q4I948, Q4ICA8, Q4P112, Q4P6N7, Q4WKH9, Q4WPW8, Q54UW5, Q5A0W7, Q5AGZ9, Q5BBV9, Q5BGK3, Q6BI60, Q6BSB8, Q6C3X6, Q6CB52, Q6CQA9, Q6CT29, Q6FSF1, Q6FU78, Q750R1, Q755G5, Q873C7, Q8AWW7, Q8STP2

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
RUVBL1	“form complex”	“NuA4 complex”	binding
RUVBL1	“form complex”	“INO80 complex”	binding
RUVBL1	“form complex”	“R2TP core co-chaperone”	binding
RUVBL1	“form complex”	“R2SP co-chaperone”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
DNA Damage Recognition in GG-NER	6	14.5×	5e-04
Nucleotide Excision Repair	5	12.1×	3e-03
Assembly and cell surface presentation of NMDA receptors	5	10.8×	4e-03
Signaling by ALK fusions and activated point mutants	8	10.2×	2e-04
Antimicrobial mechanism of IFN-stimulated genes	6	10.0×	2e-03
Post NMDA receptor activation events	5	8.6×	8e-03
MyD88 cascade initiated on plasma membrane	5	8.6×	8e-03
Deubiquitination	8	8.4×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance in response to DNA damage	7	53.1×	4e-09
regulation of chromosome organization	8	50.6×	3e-10
regulation of DNA strand elongation	7	49.8×	6e-09
regulation of double-strand break repair	11	43.2×	2e-13
positive regulation of double-strand break repair via homologous recombination	13	33.6×	3e-14
regulation of DNA replication	8	19.8×	8e-07
positive regulation of DNA repair	7	17.0×	2e-05
regulation of embryonic development	7	15.6×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

181 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	73
Likely benign	64
Benign	11

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2686028	NM_013336.4(SEC61A1):c.1141G>T (p.Glu381Ter)	Pathogenic
3337568	NM_013336.4(SEC61A1):c.1372T>G (p.Phe458Val)	Likely pathogenic
562360	NM_013336.4(SEC61A1):c.1284C>G (p.Ile428Met)	Likely pathogenic

SpliceAI

2335 predictions. Top by Δscore:

Variant	Effect	Δscore
3:128065060:G:GT	donor_gain	1.0000
3:128066943:T:TA	acceptor_gain	1.0000
3:128066949:CTCA:C	acceptor_loss	1.0000
3:128066951:CA:C	acceptor_loss	1.0000
3:128066952:AG:A	acceptor_gain	1.0000
3:128066953:GG:G	acceptor_gain	1.0000
3:128067148:GTCG:G	donor_gain	1.0000
3:128067151:GGTA:G	donor_loss	1.0000
3:128067152:G:A	donor_loss	1.0000
3:128067152:G:GG	donor_gain	1.0000
3:128067153:T:TC	donor_loss	1.0000
3:128067419:A:AG	acceptor_gain	1.0000
3:128067420:G:GG	acceptor_gain	1.0000
3:128067590:TCTC:T	donor_gain	1.0000
3:128067608:AAGAT:A	donor_gain	1.0000
3:128067610:GAT:G	donor_gain	1.0000
3:128067610:GATGT:G	donor_loss	1.0000
3:128067612:TG:T	donor_loss	1.0000
3:128067613:G:GG	donor_gain	1.0000
3:128067969:T:TA	acceptor_gain	1.0000
3:128067970:G:A	acceptor_gain	1.0000
3:128067981:A:AG	acceptor_gain	1.0000
3:128067982:G:GG	acceptor_gain	1.0000
3:128068055:AACCG:A	donor_gain	1.0000
3:128068056:ACCG:A	donor_gain	1.0000
3:128068056:ACCGG:A	donor_loss	1.0000
3:128068057:CCG:C	donor_gain	1.0000
3:128068058:CG:C	donor_gain	1.0000
3:128068059:GG:G	donor_gain	1.0000
3:128068060:G:C	donor_loss	1.0000

AlphaMissense

2994 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:128081395:A:G	L409P	1.000
3:128082483:C:A	R404M	1.000
3:128082501:C:T	G398D	1.000
3:128082559:C:G	A379P	1.000
3:128087755:C:G	R357P	1.000
3:128087761:A:G	L355P	1.000
3:128087764:A:G	L354P	1.000
3:128087779:C:A	G349V	1.000
3:128087779:C:T	G349D	1.000
3:128087780:C:G	G349R	1.000
3:128087783:G:C	H348D	1.000
3:128097318:C:G	R333P	1.000
3:128097320:G:C	N332K	1.000
3:128097320:G:T	N332K	1.000
3:128097324:G:A	S331F	1.000
3:128097324:G:T	S331Y	1.000
3:128097327:G:T	A330E	1.000
3:128097336:A:T	V327D	1.000
3:128097342:G:C	P325R	1.000
3:128097342:G:T	P325H	1.000
3:128097360:A:G	L319P	1.000
3:128097372:A:G	L315P	1.000
3:128097393:T:A	D308V	1.000
3:128097396:A:G	L307P	1.000
3:128097408:T:A	E303V	1.000
3:128097409:C:T	E303K	1.000
3:128097411:T:A	D302V	1.000
3:128097411:T:G	D302A	1.000
3:128097412:C:G	D302H	1.000
3:128097416:A:C	F300L	1.000

dbSNP variants (sampled 300 via entrez): RS1000014762 (3:128085617 C>T), RS1000143240 (3:128123371 C>A), RS1000159565 (3:128125146 C>G), RS1000211580 (3:128107451 T>C), RS1000226956 (3:128110725 C>T), RS1000239752 (3:128136237 A>C), RS1000239847 (3:128100318 C>A), RS1000246788 (3:128086814 G>A), RS1000365472 (3:128142961 A>G), RS1000383701 (3:128099397 C>T), RS1000396567 (3:128143258 C>T), RS1000396645 (3:128093624 C>T), RS1000396885 (3:128139371 G>GA), RS1000400458 (3:128125611 G>A), RS1000475768 (3:128105991 T>C)

Disease associations

OMIM: gene MIM:603449 | disease phenotypes: MIM:617056, MIM:174050, MIM:620670, MIM:620674

GenCC curated gene-disease

Mondo (4): hyperuricemic nephropathy, familial juvenile type 4 (MONDO:0014891), autosomal dominant polycystic liver disease (MONDO:0000447), immunodeficiency, common variable, 15 (MONDO:0958013), neutropenia, severe congenital, 11, autosomal dominant (MONDO:0958017)

Orphanet (2): Isolated polycystic liver disease (Orphanet:2924), Common variable immunodeficiency phenotype due to SEC61A1 deficiency (Orphanet:697417)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0006557	Polycystic liver disease

GWAS associations

84 associations (top):

Study	Trait	p-value
GCST003262_10	Post bronchodilator FEV1	4.000000e-07
GCST003262_101	Post bronchodilator FEV1	3.000000e-06
GCST003262_102	Post bronchodilator FEV1	3.000000e-06
GCST003262_103	Post bronchodilator FEV1	3.000000e-06
GCST003262_104	Post bronchodilator FEV1	3.000000e-06
GCST003262_105	Post bronchodilator FEV1	3.000000e-06
GCST003262_106	Post bronchodilator FEV1	3.000000e-06
GCST003262_107	Post bronchodilator FEV1	3.000000e-06
GCST003262_11	Post bronchodilator FEV1	5.000000e-07
GCST003262_12	Post bronchodilator FEV1	5.000000e-07
GCST003262_125	Post bronchodilator FEV1	2.000000e-06
GCST003262_132	Post bronchodilator FEV1	3.000000e-07
GCST003262_133	Post bronchodilator FEV1	5.000000e-07
GCST003262_134	Post bronchodilator FEV1	5.000000e-07
GCST003262_135	Post bronchodilator FEV1	5.000000e-07
GCST003262_137	Post bronchodilator FEV1	6.000000e-07
GCST003262_138	Post bronchodilator FEV1	6.000000e-07
GCST003262_139	Post bronchodilator FEV1	6.000000e-07
GCST003262_14	Post bronchodilator FEV1	5.000000e-07
GCST003262_143	Post bronchodilator FEV1	7.000000e-07
GCST003262_176	Post bronchodilator FEV1	2.000000e-06
GCST003262_177	Post bronchodilator FEV1	2.000000e-06
GCST003262_178	Post bronchodilator FEV1	2.000000e-06
GCST003262_179	Post bronchodilator FEV1	3.000000e-06
GCST003262_180	Post bronchodilator FEV1	4.000000e-06
GCST003262_20	Post bronchodilator FEV1	5.000000e-07
GCST003262_21	Post bronchodilator FEV1	5.000000e-07
GCST003262_5	Post bronchodilator FEV1	4.000000e-07
GCST003262_663	Post bronchodilator FEV1	3.000000e-06
GCST003262_67	Post bronchodilator FEV1	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3259467 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

9 potent at pChembl≥5 of 20 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.15	Kd	71	nM	MOLIBRESIB
5.37	Kd	4251	nM	CHEMBL3752910
5.37	ED50	4251	nM	CHEMBL3752910
5.11	IC50	7700	nM	CHEMBL5178717
5.08	Kd	8412	nM	CHEMBL5653589
5.08	ED50	8412	nM	CHEMBL5653589
5.05	IC50	9000	nM	CHEMBL3263107
5.05	IC50	9000	nM	CHEMBL5176353
5.00	IC50	1e+04	nM	ROTTLERIN

PubChem BioAssay actives

7 with measured affinity, of 70 total; 7 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179099: Binding affinity against RUVBL1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0710	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149329: Binding affinity to human RUVBL1 incubated for 45 mins by Kinobead based pull down assay	kd	4.2511	uM
[5,7-dimethyl-6-[(4-methylphenyl)methyl]pyrazolo[1,5-a]pyrimidin-3-yl]-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methanone	1891056: Inhibition of full length recombinant His6 tagged human RUVBL1 expressed in Escherichia coli Rosetta cells incubated for 70 mins in presence of ATP by ATPase assay	ic50	7.7000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149329: Binding affinity to human RUVBL1 incubated for 45 mins by Kinobead based pull down assay	kd	8.4124	uM
(2S)-2-amino-N-[4-(4-hydroxy-2-oxo-5-phenyl-1H-pyridin-3-yl)phenyl]-3-(1H-indol-3-yl)propanamide;hydrochloride	1891067: Inhibition of RUVBL1 (unknown origin)	ic50	9.0000	uM
(2S)-2-amino-N-[4-(4-hydroxy-2-oxo-5-phenyl-1H-pyridin-3-yl)phenyl]-3-(1H-indol-3-yl)propanamide	1141896: Inhibition of human recombinant his-tagged pontin expressed in Escherichia coli BL21 assessed as reduction in inorganic phosphate release after 10 mins by malachite green-based colorimetric assay	ic50	9.0000	uM
(E)-1-[6-[(3-acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2,2-dimethylchromen-8-yl]-3-phenylprop-2-en-1-one	1891067: Inhibition of RUVBL1 (unknown origin)	ic50	10.0000	uM

CTD chemical–gene interactions

67 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression	3
cobaltous chloride	decreases expression, decreases reaction	3
Valproic Acid	increases expression, affects expression	3
Arsenic Trioxide	increases expression, affects binding, decreases reaction	2
Benzo(a)pyrene	decreases expression	2
Nickel	increases expression	2
Quercetin	increases expression, decreases expression	2
T-2 Toxin	increases expression	2
Tretinoin	decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
geraniol	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chloride	decreases expression, decreases reaction	1
bleomycetin	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
jinfukang	increases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3268009	Binding	Inhibition of human recombinant his-tagged pontin expressed in Escherichia coli BL21 assessed as reduction in inorganic phosphate release at 100 uM after 10 mins by malachite green-based colorimetric assay	Design, synthesis and biological evaluation of Pontin ATPase inhibitors through a molecular docking approach. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0N2	Ubigene HeLa RUVBL1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

17 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01157858	PHASE2	COMPLETED	Everolimus and LongActing Octreotide Trial in Polycystic Livers
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT02021110	PHASE2	COMPLETED	Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
NCT05478083	PHASE2	RECRUITING	A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
NCT00426153	PHASE2/PHASE3	COMPLETED	Octreotide in Severe Polycystic Liver Disease
NCT00565097	PHASE2/PHASE3	COMPLETED	Lanreotide as Treatment of Polycystic Livers
NCT00771888	PHASE2/PHASE3	UNKNOWN	Open-Label Extension of LOCKCYST Trial
NCT01315795	PHASE2/PHASE3	COMPLETED	Lanreotide Autogel in the Treatment of Symptomatic Polycystic Liver Disease
NCT05281328	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD
NCT00934791	Not specified	TERMINATED	Polycystic Liver Disease in Kidney Transplant
NCT01354405	Not specified	COMPLETED	Somatostatin Analogues as a Volume Reducing Treatment of Polycystic Livers (RESOLVE)
NCT02173080	Not specified	COMPLETED	Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).
NCT03960710	Not specified	UNKNOWN	Automatic Segmentation of Polycystic Liver
NCT04111692	Not specified	RECRUITING	A Prospective Observational Study of Foam Sclerotherapy .
NCT04645251	Not specified	RECRUITING	Polycystic Liver Disease Registry (UK)
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT05500157	Not specified	UNKNOWN	Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts