RRP1B

Summary

RRP1B (ribosomal RNA processing 1B, HGNC:23818) is a protein-coding gene on chromosome 21q22.3, encoding Ribosomal RNA processing protein 1 homolog B (Q14684). Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1.

Enables transcription coactivator activity. Involved in cellular response to virus; positive regulation of apoptotic process; and positive regulation of transcription by RNA polymerase II. Located in chromosome; granular component; and nucleoplasm.

Source: NCBI Gene 23076 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 230 total
• Druggable target: yes
• MANE Select transcript: NM_015056

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23818
Approved symbol	RRP1B
Name	ribosomal RNA processing 1B
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	Nnp1, RRP1, PPP1R136
Ensembl gene	ENSG00000160208
Ensembl biotype	protein_coding
OMIM	610654
Entrez	23076

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000340648, ENST00000470886

RefSeq mRNA: 1 — MANE Select: NM_015056 NM_015056

CCDS: CCDS33577

Canonical transcript exons

ENST00000340648 — 16 exons

Exon	Start	End
ENSE00001050562	43672308	43672365
ENSE00001050563	43686804	43686935
ENSE00001050565	43674636	43674697
ENSE00001050567	43675034	43675163
ENSE00001050568	43673870	43673955
ENSE00001050573	43676272	43676336
ENSE00001050574	43683279	43683373
ENSE00001050575	43676733	43676914
ENSE00001050577	43684553	43684650
ENSE00001239328	43669884	43669966
ENSE00001321016	43685770	43685789
ENSE00001941645	43659560	43659794
ENSE00003526149	43690288	43690440
ENSE00003540860	43691439	43691502
ENSE00003582735	43693190	43696079
ENSE00003633685	43687516	43688240

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 95.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.5309 / max 579.2094, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189370	30.3790	1821
189371	5.1518	1519

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	95.30	gold quality
gingival epithelium	UBERON:0001949	95.24	gold quality
gingiva	UBERON:0001828	94.37	gold quality
esophagus squamous epithelium	UBERON:0006920	94.33	gold quality
visceral pleura	UBERON:0002401	93.85	gold quality
pleura	UBERON:0000977	93.79	gold quality
parietal pleura	UBERON:0002400	93.79	gold quality
squamous epithelium	UBERON:0006914	93.79	gold quality
tibia	UBERON:0000979	93.29	gold quality
epithelium of esophagus	UBERON:0001976	93.08	gold quality
pigmented layer of retina	UBERON:0001782	92.90	gold quality
endothelial cell	CL:0000115	92.36	silver quality
tendon of biceps brachii	UBERON:0008188	92.26	gold quality
skin of hip	UBERON:0001554	91.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.56	gold quality
hair follicle	UBERON:0002073	91.41	silver quality
pancreatic ductal cell	CL:0002079	91.35	gold quality
choroid plexus epithelium	UBERON:0003911	91.08	gold quality
cervix squamous epithelium	UBERON:0006922	91.02	silver quality
embryo	UBERON:0000922	90.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.59	gold quality
thymus	UBERON:0002370	90.37	gold quality
lower lobe of lung	UBERON:0008949	90.32	gold quality
epithelial cell of pancreas	CL:0000083	90.31	silver quality
epithelium of nasopharynx	UBERON:0001951	90.31	gold quality
superficial temporal artery	UBERON:0001614	90.02	gold quality
amniotic fluid	UBERON:0000173	89.89	gold quality
middle frontal gyrus	UBERON:0002702	89.81	gold quality
cortical plate	UBERON:0005343	89.74	gold quality
oral cavity	UBERON:0000167	89.41	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	10.94
E-MTAB-9801	yes	5.99
E-ANND-3	yes	4.30
E-MTAB-9689	no	338.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

90 targeting RRP1B, 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-30E-5P	100.00	76.32	3242
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-589-3P	99.91	69.62	2088

Literature-anchored findings (GeneRIF, showing 10)

• These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis. (PMID:18081427)
• RRP1B, a tumor progression and metastasis susceptibility candidate gene, is potentially a dynamic modulator of transcription and chromatin structure (PMID:19710015)
• E2F1 makes use of its transcriptional target RRP1B to activate other genes directly involved in apoptosis. (PMID:20040599)
• identified and characterized a major nucleolar pool of PP1 targeted to pre-60S ribosomal subunit processing complexes by RRP1B (PMID:20926688)
• Expression of RRP1B, PCNT, KIF21A and ADRB2 in leucocytes of Down’s syndrome subjects, was analyzed. (PMID:22552340)
• BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane. (PMID:24260471)
• Data show that RRP1B regulates metastasis associated gene expression by interacting with the transcriptional corepressors TRIM28 and HP1a, which act by recruiting chromatin-modifying enzymes. (PMID:25092915)
• Presence of Rrp1b1307TT genotype and T allele confer strong risk for breast cancer development and progression. (PMID:25277657)
• this study characterized the rRNA processing 1 homolog B (RRP1B) protein as an important cellular factor for influenza A virus transcription. (PMID:26311876)
• results suggest that SIPA1 and RRP1B germline polymorphisms are important for breast cancer prognosis (PMID:26901824)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrp1	ENSDARG00000103337
mus_musculus	Rrp1b	ENSMUSG00000058392
rattus_norvegicus	Rrp1b	ENSRNOG00000001194
drosophila_melanogaster	Nnp-1	FBGN0022069
caenorhabditis_elegans		WBGENE00008151

Paralogs (1): RRP1 (ENSG00000160214)

Protein

Protein identifiers

Ribosomal RNA processing protein 1 homolog B — Q14684 (reviewed: Q14684)

Alternative names: RRP1-like protein B

All UniProt accessions (1): Q14684

UniProt curated annotations — full annotation on UniProt →

Function. Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1. Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus. Involved in regulation of mRNA splicing. Inhibits SIPA1 GTPase activity. Involved in regulating expression of extracellular matrix genes. Associates with chromatin and may play a role in modulating chromatin structure. (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA.

Subunit / interactions. Interacts with the transcriptional activator E2F1. Interacts with serine/threonine-protein phosphatase PP1 subunits PPP1CB and PPP1CC but not with PPP1CA. Interacts with 60S ribosomal proteins RPL5 and RPL27, ribosomal processing protein RRP1/NNP1 and other nucleolar proteins including NOP2/NOL1 and FBL. Also interacts with nucleolar protein NPM1/B23. Interacts with splicing factor SRSF1 and with LUC7L3/CROP. Interacts with GTPase activator SIPA1. Interacts with CBX5/HP1alpha, H1-10, NCL, PARP1, TRIM28 and YBX3. (Microbial infection) Interacts with influenza A virus nucleoprotein NP and with RNA-directed RNA polymerase subunits PB1 and PB2.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Chromosome Nucleus.

Post-translational modifications. Citrullinated by PADI4.

Induction. By DNA damage.

Similarity. Belongs to the RRP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14684-1	1	yes
Q14684-2	2

RefSeq proteins (1): NP_055871* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010301	RRP1	Family

Pfam: PF05997

UniProt features (36 total): modified residue 17, compositionally biased region 7, region of interest 4, mutagenesis site 2, helix 2, chain 1, splice variant 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7T0Y	X-RAY DIFFRACTION	1.8
9T6L	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14684-F1	60.63	0.27

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 (17): 245, 350, 392, 394, 395, 452, 458, 513, 579, 652, 702, 706, 712, 728, 732, 735, 736

Mutagenesis-validated functional residues (2):

Position	Phenotype
684	abolishes interaction with protein phosphatase pp1 subunits ppp1cb and ppp1cc; when associated with a-686.
686	abolishes interaction with protein phosphatase pp1 subunits ppp1cb and ppp1cc; when associated with a-684.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): MODULE_52, GOBP_RIBOSOME_BIOGENESIS, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, MODULE_16, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, SCHUHMACHER_MYC_TARGETS_UP, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY

GO Biological Process (10): rRNA processing (GO:0006364), mRNA processing (GO:0006397), apoptotic process (GO:0006915), RNA splicing (GO:0008380), negative regulation of GTPase activity (GO:0034260), positive regulation of apoptotic process (GO:0043065), regulation of RNA splicing (GO:0043484), host-mediated activation of viral transcription (GO:0043923), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to virus (GO:0098586)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (9): euchromatin (GO:0000791), heterochromatin (GO:0000792), granular component (GO:0001652), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), cytosol (GO:0005829), preribosome, small subunit precursor (GO:0030688)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	3
cellular anatomical structure	3
positive regulation of DNA-templated transcription	2
chromatin	2
nuclear lumen	2
intracellular membraneless organelle	2
rRNA metabolic process	1
ribosome biogenesis	1
mRNA metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
GTPase activity	1
regulation of GTPase activity	1
negative regulation of biological process	1
negative regulation of hydrolase activity	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
host-mediated perturbation of viral transcription	1
host-mediated activation of viral process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
response to virus	1
transcription coregulator activity	1
nucleic acid binding	1
binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
cytoplasm	1
preribosome	1

Protein interactions and networks

STRING

3004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRP1B	CSTB	P04080	875
RRP1B	SIPA1	Q96FS4	769
RRP1B	PDXK	O00764	632
RRP1B	ZBTB21	Q9ULJ3	586
RRP1B	NIFK	Q9BYG3	500
RRP1B	BRIX1	Q8TDN6	498
RRP1B	RPL5	P46777	490
RRP1B	DNAJC9	Q8WXX5	486
RRP1B	HSF2BP	O75031	476
RRP1B	SRSF1	Q07955	466
RRP1B	LYAR	Q9NX58	459
RRP1B	PRR14	Q9BWN1	454
RRP1B	ARID4B	Q4LE39	451
RRP1B	EBNA1BP2	Q99848	437
RRP1B	SIN3A	Q96ST3	411

IntAct

246 interactions, top by confidence:

A	B	Type	Score
RRP1B	PPP1CC	psi-mi:“MI:0915”(physical association)	0.880
PPP1CC	RRP1B	psi-mi:“MI:0407”(direct interaction)	0.880
PPP1CC	RRP1B	psi-mi:“MI:0403”(colocalization)	0.880
RRP1B	PPP1CC	psi-mi:“MI:0914”(association)	0.880
RRP1B	PPP1CC	psi-mi:“MI:0403”(colocalization)	0.880
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
RRP1B	NPM1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RRP1B	PPP1CB	psi-mi:“MI:0915”(physical association)	0.700
PPP1CA	RRP1B	psi-mi:“MI:0407”(direct interaction)	0.670
RRP1B	E2F1	psi-mi:“MI:0914”(association)	0.650
RRP1B	E2F1	psi-mi:“MI:0915”(physical association)	0.650
E2F1	RRP1B	psi-mi:“MI:0915”(physical association)	0.650
RRP1B	SRSF1	psi-mi:“MI:0915”(physical association)	0.650
RRP1B	SRSF1	psi-mi:“MI:0403”(colocalization)	0.650
RRP1B	RPL5	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (401): RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Affinity Capture-MS), RRP1B (Proximity Label-MS), RRP1B (Biochemical Activity), RRP1B (Affinity Capture-MS)

ESM2 similar proteins: A0A494C1R9, A2AKB4, A2APT9, A6NKD2, A8MT33, B0BN44, E9PGG2, F5GYI3, O19110, O88852, P0CV98, P0CV99, P0CW00, P0CW01, Q01534, Q03386, Q0P5N2, Q12967, Q14684, Q2M329, Q3U3N0, Q5F267, Q5I0E2, Q5R5G8, Q5R866, Q5SYB0, Q5VTJ3, Q60953, Q69ZB3, Q6ZUX3, Q7TQI8, Q80VJ8, Q80VR2, Q86VY4, Q8BSI6, Q8IZJ4, Q8N831, Q8VD63, Q95LS7, Q96FG2

Diamond homologs: P35178, P56183, Q14684, Q91YK2, Q9VJZ7, Q9Y7M6, P56182, Q54WY5, Q18674

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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
Maturation of hRSV A proteins	5	28.2×	2e-05
SRP-dependent cotranslational protein targeting to membrane	17	12.6×	6e-12
Peptide chain elongation	13	12.2×	6e-09
Viral mRNA Translation	13	12.2×	6e-09
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	13	12.1×	6e-09
Selenocysteine synthesis	13	11.6×	6e-09
Eukaryotic Translation Termination	13	11.6×	6e-09
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	13	11.3×	6e-09

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal large subunit biogenesis	7	17.7×	3e-05
cytoplasmic translation	15	15.9×	3e-11
ribosomal small subunit biogenesis	11	14.3×	1e-07
mRNA stabilization	6	12.6×	1e-03
rRNA processing	12	9.7×	1e-06
negative regulation of translation	8	9.0×	6e-04
translation	15	8.8×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	159
Likely benign	23
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

2380 predictions. Top by Δscore:

Variant	Effect	Δscore
21:43659787:G:GT	donor_gain	1.0000
21:43659791:ACAG:A	donor_loss	1.0000
21:43659792:CAGGT:C	donor_loss	1.0000
21:43659793:AGG:A	donor_loss	1.0000
21:43659794:GGTG:G	donor_loss	1.0000
21:43659795:G:GA	donor_loss	1.0000
21:43659796:T:G	donor_loss	1.0000
21:43669880:CCAG:C	acceptor_loss	1.0000
21:43669881:CA:C	acceptor_loss	1.0000
21:43669882:A:G	acceptor_loss	1.0000
21:43669882:AG:A	acceptor_gain	1.0000
21:43669882:AGGAG:A	acceptor_gain	1.0000
21:43669883:GG:G	acceptor_gain	1.0000
21:43669883:GGA:G	acceptor_gain	1.0000
21:43669883:GGAGG:G	acceptor_gain	1.0000
21:43669963:ACAG:A	donor_loss	1.0000
21:43669964:CAG:C	donor_loss	1.0000
21:43669966:GG:G	donor_loss	1.0000
21:43669968:T:A	donor_loss	1.0000
21:43672292:A:AG	acceptor_gain	1.0000
21:43672293:A:G	acceptor_gain	1.0000
21:43672297:C:CA	acceptor_gain	1.0000
21:43672361:GGCTC:G	donor_gain	1.0000
21:43672362:GCTC:G	donor_gain	1.0000
21:43672362:GCTCG:G	donor_gain	1.0000
21:43672366:G:GG	donor_gain	1.0000
21:43673868:A:AG	acceptor_gain	1.0000
21:43673869:G:GG	acceptor_gain	1.0000
21:43675030:TTA:T	acceptor_loss	1.0000
21:43675031:TA:T	acceptor_loss	1.0000

AlphaMissense

5006 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:43693192:T:C	F696L	0.997
21:43693194:C:A	F696L	0.997
21:43693194:C:G	F696L	0.997
21:43659756:T:C	L31P	0.996
21:43691475:T:C	F686L	0.996
21:43691477:T:A	F686L	0.996
21:43691477:T:G	F686L	0.996
21:43693193:T:C	F696S	0.994
21:43659702:C:A	A13D	0.993
21:43669916:T:A	W55R	0.993
21:43669916:T:C	W55R	0.993
21:43693249:T:C	F715L	0.993
21:43693251:C:A	F715L	0.993
21:43693251:C:G	F715L	0.993
21:43659711:T:C	L16P	0.991
21:43669922:G:A	G57R	0.991
21:43669922:G:C	G57R	0.991
21:43659743:G:C	A27P	0.990
21:43659699:T:C	F12S	0.989
21:43659708:G:C	R15P	0.987
21:43659741:G:C	R26P	0.987
21:43673893:T:A	W99R	0.987
21:43673893:T:C	W99R	0.987
21:43659744:C:A	A27E	0.985
21:43659764:T:G	Y34D	0.985
21:43693193:T:G	F696C	0.985
21:43691476:T:C	F686S	0.984
21:43659711:T:A	L16Q	0.982
21:43659756:T:A	L31Q	0.982
21:43659765:A:C	Y34S	0.982

dbSNP variants (sampled 300 via entrez): RS1000081028 (21:43672951 A>T), RS1000153507 (21:43667499 G>A,C,T), RS1000203357 (21:43679426 G>A), RS1000208564 (21:43682672 T>A,C), RS1000270136 (21:43676196 G>A,T), RS1000275442 (21:43679768 T>A,C), RS1000297589 (21:43661973 A>G), RS1000299020 (21:43670345 G>A), RS1000407786 (21:43676431 C>A), RS1000472106 (21:43670047 C>A,G,T), RS1000547591 (21:43659226 G>A), RS1000557435 (21:43673219 G>T), RS1000617930 (21:43657980 G>A), RS1000658969 (21:43664952 G>A), RS1000723224 (21:43674911 G>T)

Disease associations

OMIM: gene MIM:610654 | disease phenotypes: MIM:616341, MIM:254800

GenCC curated gene-disease

Mondo (3): developmental and epileptic encephalopathy, 30 (MONDO:0014595), progressive myoclonus epilepsy (MONDO:0020074), breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (2): Progressive myoclonic epilepsy type 1 (Orphanet:308), Progressive myoclonic epilepsy (Orphanet:98261)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004280_2	Diastolic blood pressure	2.000000e-07
GCST004630_33	Mean corpuscular hemoglobin	2.000000e-10
GCST005196_251	Coronary artery disease	2.000000e-07
GCST006020_12	Diastolic blood pressure	9.000000e-10
GCST006021_3	Systolic blood pressure	1.000000e-07
GCST007611_7	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	2.000000e-11
GCST010002_77	Refractive error	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004527	mean corpuscular hemoglobin
EFO:0006335	systolic blood pressure

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D020191	Myoclonic Epilepsies, Progressive	C10.228.140.490.375.130.650; C10.228.140.490.493.063.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067114 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9306160	Efficacy	3	atenolol	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9306160	RRP1B	3	3.00	1	atenolol

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
5.76	Kd	1734	nM	CHEMBL5653589
5.76	ED50	1734	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	2149324: Binding affinity to human RRP1B incubated for 45 mins by Kinobead based pull down assay	kd	1.7344	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
Estradiol	increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
deoxynivalenol	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
deguelin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants, Occupational	affects expression	1
Antimycin A	increases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	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
CHEMBL5652366	Binding	Binding affinity to human RRP1B 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)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT06593951	Not specified	RECRUITING	Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
NCT06923241	Not specified	COMPLETED	Nutri-score Labelling in a UK Restaurant Setting: a Randomised Control Trial
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery