RRS1

Summary

RRS1 (regulator of ribosome synthesis 1, HGNC:17083) is a protein-coding gene on chromosome 8q13.1, encoding Ribosome biogenesis regulatory protein homolog (Q15050). Involved in ribosomal large subunit assembly. It is a common-essential gene (DepMap: required in 98.9% of cancer cell lines).

Enables 5S rRNA binding activity. Involved in several processes, including mitotic metaphase chromosome alignment; protein localization to nucleolus; and ribosomal large subunit assembly. Located in condensed nuclear chromosome; nucleolus; and nucleoplasm.

Source: NCBI Gene 23212 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 48 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_015169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17083
Approved symbol	RRS1
Name	regulator of ribosome synthesis 1
Location	8q13.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0112
Ensembl gene	ENSG00000179041
Ensembl biotype	protein_coding
OMIM	618311
Entrez	23212

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000320270

RefSeq mRNA: 1 — MANE Select: NM_015169 NM_015169

CCDS: CCDS6189

Canonical transcript exons

ENST00000320270 — 1 exons

Exon	Start	End
ENSE00001221531	66429014	66430733

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 91.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4130 / max 219.8075, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89184	25.4130	1797

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	91.61	gold quality
muscle of leg	UBERON:0001383	90.40	gold quality
layer of synovial tissue	UBERON:0007616	90.02	gold quality
body of pancreas	UBERON:0001150	89.95	gold quality
skeletal muscle tissue	UBERON:0001134	88.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.57	gold quality
mucosa of transverse colon	UBERON:0004991	87.50	gold quality
pancreas	UBERON:0001264	86.59	gold quality
muscle tissue	UBERON:0002385	86.24	gold quality
monocyte	CL:0000576	85.94	gold quality
leukocyte	CL:0000738	85.83	gold quality
endometrium epithelium	UBERON:0004811	85.48	gold quality
left uterine tube	UBERON:0001303	85.25	gold quality
body of stomach	UBERON:0001161	85.20	gold quality
heart left ventricle	UBERON:0002084	84.56	gold quality
right coronary artery	UBERON:0001625	84.26	gold quality
left ovary	UBERON:0002119	83.85	gold quality
esophagus mucosa	UBERON:0002469	83.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.75	gold quality
lower esophagus	UBERON:0013473	83.72	gold quality
quadriceps femoris	UBERON:0001377	83.70	gold quality
esophagus	UBERON:0001043	83.53	gold quality
ovary	UBERON:0000992	83.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.43	gold quality
left adrenal gland	UBERON:0001234	83.36	gold quality
left adrenal gland cortex	UBERON:0035825	83.36	gold quality
sigmoid colon	UBERON:0001159	83.33	gold quality
right ovary	UBERON:0002118	83.31	gold quality
body of uterus	UBERON:0009853	83.30	gold quality
granulocyte	CL:0000094	83.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting RRS1, 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-5692A	100.00	74.40	6850
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-3184-3P	96.96	66.91	845

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• RNA interference experiments revealed that RRS1-depleted cells show abnormalities in chromosome alignment and spindle organization, which result in mitotic delay. (PMID:19465021)
• These results suggest that the RRS1 gene plays a critical role in cell proliferation, colony formation, cell apoptosis and cell cycle distribution in human HCC cells, and that silencing of RRS1 by RNAi is a promising therapeutic approach for the treatment of HCC, and should be further developed (PMID:28849112)
• co-immunoprecipitation (CoIP) experiments showed that RRS1 knockdown activated p53 by facilitating the direct contact of MDM2 and RPL11/RPL5. Taken together, our results suggest that RRS1 may contribute to breast cancer proliferation through RPL11/MDM2-mediated p53 activation. (PMID:30320499)
• RRS1 is a novel gene related to breast cancer and has an important role in breast cancer proliferation and apoptosis (PMID:30509086)
• RRS1 Promotes Retinoblastoma Cell Proliferation and Invasion via Activating the AKT/mTOR Signaling Pathway. (PMID:33204686)
• Genomic gain of RRS1 promotes hepatocellular carcinoma through reducing the RPL11-MDM2-p53 signaling. (PMID:34433556)
• Genomic gain/methylation modification/hsa-miR-132-3p increases RRS1 overexpression in liver hepatocellular carcinoma. (PMID:37705317)
• Long noncoding RNA SNHG1 promotes breast cancer progression by regulating the miR-641/RRS1 axis. (PMID:38331968)
• The role of RRS1 in breast cancer cells metastasis and AEG-1/AKT/c-Myc signaling pathway. (PMID:39267538)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrs1	ENSDARG00000003941
mus_musculus	Rrs1	ENSMUSG00000061024
rattus_norvegicus	Rrs1	ENSRNOG00000007240
drosophila_melanogaster	CG32409	FBGN0052409
caenorhabditis_elegans		WBGENE00007617

Protein

Protein identifiers

Ribosome biogenesis regulatory protein homolog — Q15050 (reviewed: Q15050)

All UniProt accessions (1): Q15050

UniProt curated annotations — full annotation on UniProt →

Function. Involved in ribosomal large subunit assembly. May regulate the localization of the 5S RNP/5S ribonucleoprotein particle to the nucleolus.

Subunit / interactions. Component of a hexameric 5S RNP precursor complex, composed of 5S RNA, RRS1, RPF2/BXDC1, RPL5, RPL11 and HEATR3; this complex acts as a precursor for ribosome assembly.

Subcellular location. Nucleus. Nucleolus.

Post-translational modifications. Citrullinated by PADI4.

Similarity. Belongs to the RRS1 family.

RefSeq proteins (1): NP_055984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007023	Ribosom_reg	Family

Pfam: PF04939

UniProt features (16 total): compositionally biased region 4, cross-link 3, sequence variant 3, modified residue 3, region of interest 2, chain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FKW	ELECTRON MICROSCOPY	2.5
8FKX	ELECTRON MICROSCOPY	2.59
8FKY	ELECTRON MICROSCOPY	2.67
8FKQ	ELECTRON MICROSCOPY	2.76
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82
8RL2	ELECTRON MICROSCOPY	2.84
8FKP	ELECTRON MICROSCOPY	2.85
8FKS	ELECTRON MICROSCOPY	2.88
8FKR	ELECTRON MICROSCOPY	2.89
8FL0	ELECTRON MICROSCOPY	2.91
9QIW	ELECTRON MICROSCOPY	3.04
8IR1	ELECTRON MICROSCOPY	3.3
8IR3	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15050-F1	78.45	0.34

Functional residue map

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

Post-translational modifications (6): 154, 226, 266, 1, 5, 273

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 260 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RIBOSOME_BIOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, GOBP_CHROMOSOME_LOCALIZATION, GOBP_RIBOSOME_ASSEMBLY, PUJANA_CHEK2_PCC_NETWORK, SCHUHMACHER_MYC_TARGETS_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_ORGANELLE_FISSION, GOBP_RIBOSOMAL_LARGE_SUBUNIT_ASSEMBLY, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS

GO Biological Process (8): ribosomal large subunit assembly (GO:0000027), endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000447), hematopoietic progenitor cell differentiation (GO:0002244), mitotic metaphase chromosome alignment (GO:0007080), ribosomal large subunit biogenesis (GO:0042273), regulation of signal transduction by p53 class mediator (GO:1901796), protein localization to nucleolus (GO:1902570), ribosome biogenesis (GO:0042254)

GO Molecular Function (3): RNA binding (GO:0003723), 5S rRNA binding (GO:0008097), protein binding (GO:0005515)

GO Cellular Component (6): condensed nuclear chromosome (GO:0000794), nucleoplasm (GO:0005654), nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), preribosome, large subunit precursor (GO:0030687), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoprotein complex biogenesis	2
nuclear lumen	2
intracellular membrane-bounded organelle	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal large subunit biogenesis	1
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1
maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1
endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1
hemopoiesis	1
cell differentiation	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
ribosome biogenesis	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
protein localization to nucleus	1
nucleic acid binding	1
rRNA binding	1
binding	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
cellular anatomical structure	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1
preribosome	1

Protein interactions and networks

STRING

2546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRS1	RPF2	Q9H7B2	984
RRS1	RPL11	P25121	810
RRS1	RPL5	P46777	729
RRS1	BOP1	Q14137	705
RRS1	RPS2	P15880	659
RRS1	WDR12	Q9GZL7	625
RRS1	CTNNB1	P35222	605
RRS1	NXN	Q6DKJ4	596
RRS1	MTDH	Q86UE4	594
RRS1	EBNA1BP2	Q99848	565
RRS1	NIP7	Q9Y221	490
RRS1	BRIX1	Q8TDN6	478
RRS1	RMDN1	Q96DB5	475
RRS1	DDX27	Q96GQ7	475
RRS1	RRP1	P56182	471

IntAct

185 interactions, top by confidence:

A	B	Type	Score
RRS1	APPBP2	psi-mi:“MI:0915”(physical association)	0.780
APPBP2	RRS1	psi-mi:“MI:0915”(physical association)	0.780
RPF2	RRS1	psi-mi:“MI:0915”(physical association)	0.670
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
RPL7A	NOP56	psi-mi:“MI:0914”(association)	0.640
NOP56	RPL7A	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
SDCBP	RRS1	psi-mi:“MI:0915”(physical association)	0.560
RPL28	MAGEB2	psi-mi:“MI:0914”(association)	0.560
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
SURF2	HEXIM1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
NHSL3	NCK2	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
RPL7A	NVL	psi-mi:“MI:0914”(association)	0.530
H1-1	SURF6	psi-mi:“MI:0914”(association)	0.530
RPL11	NVL	psi-mi:“MI:0914”(association)	0.530

BioGRID (548): RRS1 (Two-hybrid), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Affinity Capture-MS), RRS1 (Two-hybrid), EBNA1BP2 (Co-fractionation), NIFK (Co-fractionation)

ESM2 similar proteins: A1A5P2, A6QNR1, A8WY26, D3ZND0, O15213, O59678, P27672, P78316, Q0V8M0, Q15050, Q24K12, Q28IV8, Q2KIH4, Q2KII6, Q3T0Q8, Q3T0Z5, Q3UFY0, Q4KLC4, Q5M985, Q5RAS1, Q5RJT2, Q5TAP6, Q5TJE7, Q5ZKM1, Q640M1, Q6EJB6, Q6P0I6, Q6PFJ1, Q8BK35, Q8IY81, Q8N9T8, Q8NEJ9, Q8R3N1, Q8VDQ9, Q96BZ8, Q96EU6, Q9BRP8, Q9BRR8, Q9BVJ6, Q9C086

Diamond homologs: A1A5P2, A8WY26, G0SCH6, O59678, Q08746, Q15050, Q2KIH4, Q869Q2, Q9CYH6, Q9SH88, Q9XVT0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 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
Peptide chain elongation	18	19.0×	2e-16
Viral mRNA Translation	18	19.0×	2e-16
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	18	18.8×	2e-16
Selenocysteine synthesis	18	18.0×	3e-16
Eukaryotic Translation Termination	18	18.0×	3e-16
Eukaryotic Translation Initiation	7	18.0×	2e-06
Cap-dependent Translation Initiation	7	18.0×	2e-06
SARS-CoV-1 modulates host translation machinery	7	18.0×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	6	40.4×	6e-07
chromosome condensation	7	35.3×	1e-07
cytoplasmic translation	19	21.1×	3e-17
ribosomal large subunit biogenesis	7	18.6×	1e-05
ribosomal small subunit biogenesis	11	15.0×	4e-08
rRNA processing	16	13.6×	1e-11
translation	19	11.7×	1e-12
regulation of signal transduction by p53 class mediator	5	11.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

57 predictions. Top by Δscore:

Variant	Effect	Δscore
8:66429606:G:GC	acceptor_gain	0.6800
8:66429777:G:GT	donor_gain	0.4700
8:66429826:TGGGG:T	acceptor_gain	0.4400
8:66430527:A:AG	acceptor_gain	0.4400
8:66429770:GA:G	donor_gain	0.4200
8:66430040:G:GT	donor_gain	0.4000
8:66429631:T:TA	acceptor_gain	0.3900
8:66429633:G:GC	acceptor_gain	0.3700
8:66430043:GAAAA:G	donor_gain	0.3700
8:66430223:G:GT	donor_gain	0.3700
8:66430529:T:G	acceptor_gain	0.3700
8:66429772:G:GG	donor_gain	0.3600
8:66430072:G:T	donor_gain	0.3500
8:66429776:G:GT	donor_gain	0.3300
8:66429887:G:GT	donor_gain	0.3300
8:66430044:A:T	donor_gain	0.3100
8:66429676:TGGCC:T	donor_gain	0.2900
8:66429777:G:T	donor_gain	0.2900
8:66430223:G:T	donor_gain	0.2900
8:66430229:A:AG	donor_gain	0.2900
8:66429631:TGG:T	acceptor_gain	0.2800
8:66429771:A:AG	donor_gain	0.2800
8:66429630:TTGG:T	acceptor_gain	0.2600
8:66429814:C:CA	acceptor_gain	0.2600
8:66429827:GGGGC:G	acceptor_gain	0.2600
8:66429828:GGGCG:G	acceptor_gain	0.2600
8:66430071:G:GT	donor_gain	0.2600
8:66429532:ACGAG:A	donor_loss	0.2500
8:66429533:CGAGG:C	donor_loss	0.2500
8:66429534:GAGG:G	donor_loss	0.2500

AlphaMissense

2359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:66429480:T:C	F117L	0.999
8:66429482:C:A	F117L	0.999
8:66429482:C:G	F117L	0.999
8:66429834:T:C	F235L	0.998
8:66429836:T:A	F235L	0.998
8:66429836:T:G	F235L	0.998
8:66429473:G:C	W114C	0.997
8:66429473:G:T	W114C	0.997
8:66429481:T:G	F117C	0.997
8:66429494:G:C	K121N	0.997
8:66429494:G:T	K121N	0.997
8:66429481:T:C	F117S	0.996
8:66429499:T:C	I123T	0.996
8:66429697:G:C	R189P	0.995
8:66429597:T:A	W156R	0.994
8:66429597:T:C	W156R	0.994
8:66429686:C:A	N185K	0.994
8:66429686:C:G	N185K	0.994
8:66429471:T:A	W114R	0.993
8:66429471:T:C	W114R	0.993
8:66429665:G:C	K178N	0.993
8:66429665:G:T	K178N	0.993
8:66429700:T:C	L190P	0.993
8:66429564:G:C	G145R	0.992
8:66429642:T:C	F171L	0.991
8:66429644:C:A	F171L	0.991
8:66429644:C:G	F171L	0.991
8:66429215:G:C	K28N	0.989
8:66429215:G:T	K28N	0.989
8:66429483:G:C	A118P	0.989

dbSNP variants (sampled 300 via entrez): RS1000127524 (8:66428593 A>C), RS1000219802 (8:66431036 T>C,G), RS1000268955 (8:66431222 G>GT), RS1002159636 (8:66428315 T>C), RS1002190767 (8:66428771 C>T), RS1002873334 (8:66430636 G>A), RS1003185529 (8:66429823 C>T), RS1003394251 (8:66430364 C>T), RS1003444119 (8:66430704 T>G), RS1003483738 (8:66429571 A>C), RS1003908775 (8:66429328 G>A), RS1004642190 (8:66428907 A>C), RS1005219867 (8:66427628 G>C), RS1006651395 (8:66430558 C>T), RS1007806062 (8:66428567 C>G,T)

Disease associations

OMIM: gene MIM:618311 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008103_169	Bipolar disorder	7.000000e-06
GCST008115_21	Bipolar I disorder	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067235 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.27	Kd	53.89	nM	CHEMBL5653589
7.27	ED50	53.89	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149325: Binding affinity to human RRS1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0539	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
bisphenol A	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression, affects expression	4
(+)-JQ1 compound	decreases expression	3
Acetaminophen	decreases expression, increases expression	3
Estradiol	increases expression	3
cobaltous chloride	decreases expression, decreases reaction	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cadmium Chloride	decreases expression	2
Genistein	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
TAK-243	decreases sumoylation	1
deoxynivalenol	increases expression	1
lead acetate	increases expression	1
methylparaben	decreases expression	1
afimoxifene	decreases reaction, increases expression	1
zinc chloride	decreases expression, decreases reaction	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, increases expression	1
sulindac sulfide	increases expression	1
cupric chloride	increases expression	1
nivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
deguelin	increases expression	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652367	Binding	Binding affinity to human RRS1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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