RRP1

Summary

RRP1 (ribosomal RNA processing 1, HGNC:18785) is a protein-coding gene on chromosome 21q22.3, encoding Ribosomal RNA processing protein 1 homolog A (P56182). Plays a critical role in the generation of 28S rRNA. It is a selective cancer dependency (DepMap: 86.8% of cell lines).

The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA.

Source: NCBI Gene 8568 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 118 total
• Cancer dependency (DepMap): dependent in 86.8% of screened cell lines
• MANE Select transcript: NM_003683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18785
Approved symbol	RRP1
Name	ribosomal RNA processing 1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	NNP-1, Nop52, NOP52, RRP1A, D21S2056E
Ensembl gene	ENSG00000160214
Ensembl biotype	protein_coding
OMIM	610653
Entrez	8568

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000467112, ENST00000471909, ENST00000473988, ENST00000475534, ENST00000483896, ENST00000492638, ENST00000497547, ENST00000856884, ENST00000856885, ENST00000856886, ENST00000856887, ENST00000917586, ENST00000917587, ENST00000917588, ENST00000917589

RefSeq mRNA: 1 — MANE Select: NM_003683 NM_003683

CCDS: CCDS42951

Canonical transcript exons

ENST00000497547 — 13 exons

Exon	Start	End
ENSE00001867462	43789577	43789762
ENSE00003460664	43795189	43795250
ENSE00003493319	43799570	43799649
ENSE00003497110	43803512	43805293
ENSE00003527287	43800862	43800881
ENSE00003546458	43797907	43798100
ENSE00003549420	43797422	43797551
ENSE00003564822	43792672	43792729
ENSE00003577332	43791350	43791432
ENSE00003580595	43793319	43793404
ENSE00003626947	43797631	43797695
ENSE00003627514	43800517	43800614
ENSE00003680163	43802274	43802387

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 93.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7799 / max 286.3154, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189397	23.8000	1811
189399	1.0537	591
189398	0.9262	579

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	93.15	gold quality
gingival epithelium	UBERON:0001949	90.10	gold quality
lower esophagus mucosa	UBERON:0035834	89.92	gold quality
esophagus mucosa	UBERON:0002469	89.85	gold quality
tongue squamous epithelium	UBERON:0006919	89.66	gold quality
skin of leg	UBERON:0001511	88.04	gold quality
buccal mucosa cell	CL:0002336	87.85	gold quality
skin of abdomen	UBERON:0001416	87.76	gold quality
gingiva	UBERON:0001828	87.52	gold quality
gastrocnemius	UBERON:0001388	86.98	gold quality
cerebellar vermis	UBERON:0004720	86.58	gold quality
sural nerve	UBERON:0015488	86.24	gold quality
esophagus	UBERON:0001043	86.09	gold quality
muscle of leg	UBERON:0001383	86.06	gold quality
prefrontal cortex	UBERON:0000451	86.04	gold quality
ganglionic eminence	UBERON:0004023	85.98	gold quality
zone of skin	UBERON:0000014	85.80	gold quality
granulocyte	CL:0000094	85.70	gold quality
squamous epithelium	UBERON:0006914	85.69	gold quality
ventricular zone	UBERON:0003053	85.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.51	gold quality
cortical plate	UBERON:0005343	85.36	gold quality
olfactory bulb	UBERON:0002264	85.32	silver quality
right lobe of liver	UBERON:0001114	85.29	gold quality
right frontal lobe	UBERON:0002810	85.12	gold quality
stromal cell of endometrium	CL:0002255	85.04	gold quality
body of pancreas	UBERON:0001150	85.01	gold quality
type B pancreatic cell	CL:0000169	84.95	silver quality
left ovary	UBERON:0002119	84.88	gold quality
minor salivary gland	UBERON:0001830	84.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-27	no	4.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting RRP1, 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-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4479	82.48	59.28	12

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 86.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• NNP-1 expression in neuroblastoma (PMID:12209604)
• p32 is a new rRNA maturation factor involved in the remodeling from pre-90S particles to pre-40S and pre-60S particles that requires the exchange of FBL for Nop52. (PMID:21536856)
• The data suggest that RRP1 is involved not only in competitive binding with fibrillarin to C1QBP on 90S but also in site 2 cleavage in ITS1 of pre-rRNAs at early stages of human ribosome biogenesis. (PMID:25969445)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrp1	ENSDARG00000103337
mus_musculus	Rrp1	ENSMUSG00000061032
rattus_norvegicus	Rrp1	ENSRNOG00000001203
drosophila_melanogaster	Nnp-1	FBGN0022069
caenorhabditis_elegans		WBGENE00008151

Paralogs (1): RRP1B (ENSG00000160208)

Protein

Protein identifiers

Ribosomal RNA processing protein 1 homolog A — P56182 (reviewed: P56182)

Alternative names: Novel nuclear protein 1, Nucleolar protein Nop52, RRP1-like protein

All UniProt accessions (2): P56182, D6RE82

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in the generation of 28S rRNA.

Subunit / interactions. Interacts with C1QBP. Interacts with RRP1B.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Ubiquitously expressed in fetal and adult tissues.

Post-translational modifications. Methylated at Gln-427 by N6AMT1.

Similarity. Belongs to the RRP1 family.

RefSeq proteins (1): NP_003674* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010301	RRP1	Family

Pfam: PF05997

UniProt features (18 total): modified residue 7, compositionally biased region 5, region of interest 2, sequence variant 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FKT	ELECTRON MICROSCOPY	2.81
8FKP	ELECTRON MICROSCOPY	2.85
8FKR	ELECTRON MICROSCOPY	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56182-F1	75.97	0.56

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 (7): 250, 251, 383, 412, 427, 245, 247

Mutagenesis-validated functional residues (1):

Position	Phenotype
427	abolishes methylation by n6amt1.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 103 (showing top): GOBP_RIBOSOME_BIOGENESIS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, VANTVEER_BREAST_CANCER_ESR1_DN, chr21q22, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, VANTVEER_BREAST_CANCER_BRCA1_UP, REACTOME_METABOLISM_OF_RNA, GOCC_PRERIBOSOME, GOCC_NUCLEOLUS, GOCC_RIBONUCLEOPROTEIN_COMPLEX, LINDGREN_BLADDER_CANCER_CLUSTER_1_DN, MANALO_HYPOXIA_DN, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, SENGUPTA_EBNA1_ANTICORRELATED

GO Biological Process (1): rRNA processing (GO:0006364)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), chromosome (GO:0005694), nucleolus (GO:0005730), preribosome, small subunit precursor (GO:0030688)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
preribosome	1

Protein interactions and networks

STRING

2010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRP1	FBL	P22087	895
RRP1	NUCLEOLIN	P19338	862
RRP1	CSTB	P04080	802
RRP1	NPM1	P06748	776
RRP1	MKI67	P46013	763
RRP1	NOL12	Q9UGY1	531
RRP1	BOP1	Q14137	522
RRP1	UBTF	P17480	518
RRP1	SIPA1	Q96FS4	515
RRP1	NIFK	Q9BYG3	505
RRP1	BRIX1	Q8TDN6	482
RRP1	RRS1	Q15050	471
RRP1	NOP56	O00567	454
RRP1	POLI	Q9UNA4	447
RRP1	EXOSC10	Q01780	441

IntAct

119 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
SPANXN2	RRP1	psi-mi:“MI:0915”(physical association)	0.560
RRP1	SPANXN2	psi-mi:“MI:0915”(physical association)	0.560
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
CLMP	UTP20	psi-mi:“MI:0914”(association)	0.530
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
MOGS	RRP1	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
RRP1	RRP1B	psi-mi:“MI:0915”(physical association)	0.500
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
	AP3D1	psi-mi:“MI:0914”(association)	0.350

BioGRID (189): RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-RNA), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), RRP1 (Biochemical Activity), RRP1 (Biochemical Activity), RRP1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GU71, A6QPI4, B2RV13, D4A6L0, E1BBQ2, F1LQY6, G3UW36, O08856, P15382, P53801, P55199, P56182, Q08CB3, Q0VF94, Q148E1, Q17RQ9, Q2KJ58, Q32Q90, Q4R5F9, Q4V8A6, Q4VA36, Q5I0I4, Q5NVI6, Q5R8Q2, Q5T6X4, Q5T848, Q5XII8, Q68EN5, Q6P767, Q8C419, Q8CHT6, Q8R143, Q8R1T1, Q8TBN0, Q8VDV3, Q8WUX9, Q90YH8, Q91WM6, Q91ZP9, Q96IL0

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 164 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
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	5	16.0×	2e-03
Maturation of spike protein	5	12.7×	3e-03
Maturation of DENV proteins	5	10.1×	6e-03
SRP-dependent cotranslational protein targeting to membrane	9	8.6×	3e-04
Major pathway of rRNA processing in the nucleolus and cytosol	12	7.0×	7e-05
SARS-CoV-2 Infection	8	6.1×	3e-03
SARS-CoV Infections	9	4.8×	6e-03
Viral Infection Pathways	14	4.1×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal large subunit biogenesis	5	15.5×	3e-03
ribosomal small subunit biogenesis	8	12.7×	2e-04
autophagosome maturation	5	12.3×	7e-03
cytoplasmic translation	7	9.1×	3e-03
rRNA processing	8	7.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	13
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2880 predictions. Top by Δscore:

Variant	Effect	Δscore
21:43789719:G:GT	donor_gain	1.0000
21:43791346:GCA:G	acceptor_loss	1.0000
21:43791347:CA:C	acceptor_loss	1.0000
21:43791348:A:C	acceptor_loss	1.0000
21:43792728:GC:G	donor_gain	1.0000
21:43797416:CCTCA:C	acceptor_loss	1.0000
21:43797417:CTCAG:C	acceptor_loss	1.0000
21:43797418:TCAG:T	acceptor_loss	1.0000
21:43797419:CAG:C	acceptor_loss	1.0000
21:43797420:A:AC	acceptor_loss	1.0000
21:43797420:A:AG	acceptor_gain	1.0000
21:43797421:G:GT	acceptor_gain	1.0000
21:43797421:GA:G	acceptor_gain	1.0000
21:43797421:GAC:G	acceptor_gain	1.0000
21:43797421:GACA:G	acceptor_gain	1.0000
21:43797548:GGAG:G	donor_gain	1.0000
21:43797549:GAG:G	donor_gain	1.0000
21:43797549:GAGG:G	donor_gain	1.0000
21:43797550:AGGT:A	donor_loss	1.0000
21:43797551:GGTG:G	donor_loss	1.0000
21:43797552:GTGA:G	donor_loss	1.0000
21:43797553:T:A	donor_loss	1.0000
21:43797692:AGGA:A	donor_gain	1.0000
21:43797693:GGA:G	donor_gain	1.0000
21:43797693:GGAG:G	donor_gain	1.0000
21:43797694:GA:G	donor_gain	1.0000
21:43797694:GAG:G	donor_gain	1.0000
21:43797696:G:GG	donor_gain	1.0000
21:43797700:GTG:G	donor_gain	1.0000
21:43797902:CTCA:C	acceptor_loss	1.0000

AlphaMissense

3022 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:43793363:T:A	W107R	0.996
21:43793363:T:C	W107R	0.996
21:43791382:T:A	W56R	0.995
21:43791382:T:C	W56R	0.995
21:43793394:A:T	K117I	0.995
21:43791388:G:A	G58R	0.993
21:43791388:G:C	G58R	0.993
21:43791406:T:A	W64R	0.993
21:43791406:T:C	W64R	0.993
21:43791387:A:C	K57N	0.992
21:43791387:A:T	K57N	0.992
21:43791416:A:T	D67V	0.992
21:43791394:T:C	F60L	0.991
21:43791396:T:A	F60L	0.991
21:43791396:T:G	F60L	0.991
21:43791408:G:C	W64C	0.991
21:43791408:G:T	W64C	0.991
21:43791415:G:C	D67H	0.991
21:43789670:C:A	A14D	0.990
21:43791386:A:T	K57I	0.990
21:43793384:C:A	R114S	0.990
21:43793393:A:G	K117E	0.990
21:43793396:T:C	F118L	0.990
21:43793398:C:A	F118L	0.990
21:43793398:C:G	F118L	0.990
21:43797529:T:C	L177P	0.990
21:43791416:A:C	D67A	0.989
21:43793395:A:C	K117N	0.989
21:43793395:A:T	K117N	0.989
21:43791389:G:A	G58E	0.988

dbSNP variants (sampled 300 via entrez): RS1000510223 (21:43794239 C>G,T), RS1001065902 (21:43798697 A>G), RS1001150679 (21:43792412 T>A), RS1001182464 (21:43804155 G>T), RS1001410340 (21:43795918 G>C), RS1001689799 (21:43805196 A>G), RS1002182901 (21:43805393 C>G), RS1002685184 (21:43791215 C>G,T), RS1002821438 (21:43797752 C>T), RS1003039309 (21:43795748 T>C), RS1003132642 (21:43795967 G>A,C), RS1003138995 (21:43788280 C>A,G), RS1003195147 (21:43797258 C>G,T), RS1003284225 (21:43792495 G>A), RS1003305341 (21:43804119 T>C)

Disease associations

OMIM: gene MIM:610653 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
deoxynivalenol	increases expression	1
trichostatin A	affects expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Phenobarbital	affects expression	1
Ribonucleotides	affects binding	1
Selenium	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Toluene	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	affects cotreatment, increases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

11 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
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