RRP9

Summary

RRP9 (ribosomal RNA processing 9, U3 small nucleolar RNA binding protein, HGNC:16829) is a protein-coding gene on chromosome 3p21.2, encoding U3 small nucleolar RNA-interacting protein 2 (O43818). Component of a nucleolar small nuclear ribonucleoprotein particle (snoRNP) thought to participate in the processing and modification of pre-ribosomal RNA (pre-rRNA). It is a selective cancer dependency (DepMap: 89.1% of cell lines).

This gene encodes a member of the WD-repeat protein family. The encoded protein is a component of the nucleolar small nuclear ribonucleoprotein particle (snoRNP) and is essential for 18s rRNA processing during ribosome synthesis. It contains seven WD domains required for nucleolar localization and specific interaction with the U3 small nucleolar RNA (U3 snoRNA).

Source: NCBI Gene 9136 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 96 total
• Cancer dependency (DepMap): dependent in 89.1% of screened cell lines
• MANE Select transcript: NM_004704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16829
Approved symbol	RRP9
Name	ribosomal RNA processing 9, U3 small nucleolar RNA binding protein
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Aliases	U3-55K
Ensembl gene	ENSG00000114767
Ensembl biotype	protein_coding
OMIM	620013
Entrez	9136

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000232888, ENST00000897235, ENST00000897236, ENST00000897237, ENST00000940583, ENST00000940584, ENST00000940585, ENST00000940586, ENST00000940587, ENST00000958854, ENST00000958855

RefSeq mRNA: 1 — MANE Select: NM_004704 NM_004704

CCDS: CCDS2837

Canonical transcript exons

ENST00000232888 — 15 exons

Exon	Start	End
ENSE00000770209	51933708	51933781
ENSE00000770211	51934472	51934551
ENSE00000770213	51934631	51934776
ENSE00000770215	51935197	51935259
ENSE00000770217	51935342	51935476
ENSE00000770218	51935592	51935692
ENSE00000770219	51936257	51936349
ENSE00000770220	51936431	51936555
ENSE00000770221	51937192	51937318
ENSE00000770223	51937545	51937586
ENSE00000770225	51937669	51937736
ENSE00000770227	51938095	51938204
ENSE00000770229	51941409	51941491
ENSE00001081277	51941781	51941904
ENSE00001249647	51933429	51933599

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 88.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8651 / max 144.9108, expressed in 1794 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42370	17.8355	1792
42371	1.0295	679

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	88.35	gold quality
mucosa of transverse colon	UBERON:0004991	87.57	gold quality
muscle of leg	UBERON:0001383	87.07	gold quality
left adrenal gland cortex	UBERON:0035825	86.92	gold quality
left uterine tube	UBERON:0001303	86.81	gold quality
left adrenal gland	UBERON:0001234	86.75	gold quality
right adrenal gland	UBERON:0001233	86.69	gold quality
right adrenal gland cortex	UBERON:0035827	86.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.00	gold quality
ectocervix	UBERON:0012249	85.99	gold quality
right ovary	UBERON:0002118	85.58	gold quality
granulocyte	CL:0000094	85.48	gold quality
omental fat pad	UBERON:0010414	85.43	gold quality
adrenal cortex	UBERON:0001235	85.41	gold quality
peritoneum	UBERON:0002358	85.38	gold quality
upper lobe of left lung	UBERON:0008952	85.23	gold quality
skin of abdomen	UBERON:0001416	85.10	gold quality
left ovary	UBERON:0002119	84.93	gold quality
tibial nerve	UBERON:0001323	84.89	gold quality
endometrium epithelium	UBERON:0004811	84.80	gold quality
apex of heart	UBERON:0002098	84.77	gold quality
skin of leg	UBERON:0001511	84.73	gold quality
esophagus mucosa	UBERON:0002469	84.60	gold quality
left coronary artery	UBERON:0001626	84.58	gold quality
body of uterus	UBERON:0009853	84.50	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.28	gold quality
adrenal gland	UBERON:0002369	84.20	gold quality
endocervix	UBERON:0000458	83.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.91	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.91	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: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• Mammalian and yeast U3 snoRNPs are matured in specific and related nuclear compartments. (PMID:12032086)
• the frequencies of African American race and male sex are greater among systemic sclerosis patients with anti-U3 RNP antibody than those without (PMID:19333934)
• Data show that U3 snoRNP assembly, and therefore U3 snoRNA accumulation, is regulated through the U3-specific protein hU3-55K. (PMID:21505065)
• Neddylation modification of the U3 snoRNA-binding protein RRP9 by Smurf1 promotes tumorigenesis. (PMID:34662580)
• RRP9 and DDX21 as new biomarkers of colorectal cancer. (PMID:37904456)
• Joint effect of RRP9 and DDX21 on development of colorectal cancer and keloid. (PMID:37988222)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrp9	ENSDARG00000041991
mus_musculus	Rrp9	ENSMUSG00000041506
rattus_norvegicus	Rrp9	ENSRNOG00000012927
drosophila_melanogaster	U3-55K	FBGN0053505
caenorhabditis_elegans	Y54E5B.2	WBGENE00013204
caenorhabditis_elegans		WBGENE00020171

Protein

Protein identifiers

U3 small nucleolar RNA-interacting protein 2 — O43818 (reviewed: O43818)

Alternative names: RRP9 homolog, U3 small nucleolar ribonucleoprotein-associated 55 kDa protein

All UniProt accessions (1): O43818

UniProt curated annotations — full annotation on UniProt →

Function. Component of a nucleolar small nuclear ribonucleoprotein particle (snoRNP) thought to participate in the processing and modification of pre-ribosomal RNA (pre-rRNA). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Interacts specifically with the U3 small nucleolar RNA (U3 snoRNA). Binds a sub-fragment of the U3 snoRNA surrounding the B/C motif (3UBC). This association with the U3BC RNA is dependent on the binding of a protein called 15.5K to the box B/C motif. The association of the protein with the U3BC RNA was found to be also dependent on a conserved RNA structure that flanks the box B/C motif. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Nucleus. Nucleolus.

Post-translational modifications. Acetylation at Lys-12 and Lys-25 by KAT2B/PCAF under stress impairs pre-rRNA processing. Deacetylation by SIRT7 enhances RRP9-binding to U3 snoRNA, which is a prerequisite for pre-rRNA processing.

Domain organisation. The WD domains are required for nucleolar localization and U3 small nucleolar RNAs binding.

Similarity. Belongs to the WD repeat RRP9 family.

RefSeq proteins (1): NP_004695* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR039241	Rrp9-like	Family

Pfam: PF00400

UniProt features (62 total): strand 30, repeat 7, modified residue 7, turn 5, mutagenesis site 4, sequence variant 2, helix 2, chain 1, compositionally biased region 1, cross-link 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4J0W	X-RAY DIFFRACTION	1.7
4JXM	X-RAY DIFFRACTION	1.92
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43818-F1	84.22	0.69

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 (8): 10, 12, 25, 50, 51, 53, 57, 113

Mutagenesis-validated functional residues (4):

Position	Phenotype
12	mimics acetylation, leading to impaired rrna processing; when associated with q-25.
12	impaired acetylation, leading to promote rrna processing; when associated with r-25.
25	mimics acetylation, leading to impaired rrna processing; when associated with q-12.
25	impaired acetylation, leading to promote rrna processing; when associated with r-12.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 180 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, GOBP_RIBOSOME_BIOGENESIS, MODULE_151, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, MORF_BRCA1, MATTIOLI_MGUS_VS_PCL, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MODULE_16, BILD_HRAS_ONCOGENIC_SIGNATURE, MODULE_388, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN

GO Biological Process (2): rRNA processing (GO:0006364), ribosomal small subunit biogenesis (GO:0042274)

GO Molecular Function (4): RNA binding (GO:0003723), snoRNA binding (GO:0030515), U3 snoRNA binding (GO:0034511), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), nucleolus (GO:0005730), box C/D methylation guide snoRNP complex (GO:0031428), small-subunit processome (GO:0032040), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribosome biogenesis	2
nuclear lumen	2
RNA processing	1
rRNA metabolic process	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
RNA binding	1
snoRNA binding	1
binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
box C/D RNP complex	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRP9	NOP56	O00567	965
RRP9	NOP58	Q9Y2X3	964
RRP9	SNU13	P55769	941
RRP9	FBL	P22087	939
RRP9	MPHOSPH10	O00566	788
RRP9	NOP14	P78316	708
RRP9	NAT10	Q9H0A0	703
RRP9	HEATR1	Q9H583	665
RRP9	BMS1	Q14692	645
RRP9	RCL1	Q9Y2P8	626
RRP9	FCF1	Q9Y324	626
RRP9	UTP4	Q969X6	620
RRP9	PDCD11	Q14690	608
RRP9	KRR1	Q13601	607
RRP9	NOL6	Q9H6R4	601

IntAct

54 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
RRP9	NOP56	psi-mi:“MI:0915”(physical association)	0.560
EED	EPOP	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
N	RRP9	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CSNK2A1	RRP9	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RRP9	LMNA	psi-mi:“MI:0915”(physical association)	0.400
UBLCP1	RRP9	psi-mi:“MI:0915”(physical association)	0.400
Snu13		psi-mi:“MI:0915”(physical association)	0.400
	RRP9	psi-mi:“MI:0915”(physical association)	0.400
Tpx2	NFKBIE	psi-mi:“MI:0914”(association)	0.350
Fbl	COPS8	psi-mi:“MI:0914”(association)	0.350
Cul4a	GPS1	psi-mi:“MI:0914”(association)	0.350
NES	RPL10	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
TRADD	HNRNPCL2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
FBL	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PPAN	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
TRA2A	GAPDHS	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
MAP2K1	HNRNPDL	psi-mi:“MI:0914”(association)	0.350

BioGRID (193): RRP9 (Affinity Capture-MS), RRP9 (Affinity Capture-MS), RRP9 (Affinity Capture-MS), RRP9 (Affinity Capture-MS), DCAF13 (Co-fractionation), HMGN5 (Co-fractionation), IMP3 (Co-fractionation), NOL6 (Co-fractionation), PWP2 (Co-fractionation), RRP9 (Co-fractionation), RRP9 (Co-fractionation), TBL3 (Co-fractionation), RRP9 (Synthetic Lethality), RRP9 (Affinity Capture-MS), RRP9 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A5D7H2, A6QLH6, O00459, O08908, O14908, O43374, O43818, O62683, O70422, O70585, O75146, O88448, O95049, O97583, P23092, P23726, P58405, P60027, P70268, Q13033, Q15334, Q16512, Q1JQD7, Q2KJ58, Q32LP0, Q3KRC5, Q5M9F8, Q5RB75, Q5XIS9, Q5ZIW1, Q63433, Q63788, Q6PFQ7, Q8BZ03, Q8IVD9, Q8NEG4, Q8R5M0, Q8TBN0, Q8TF64

Diamond homologs: A4IIX9, A8WGF4, G0SC29, O13982, O43818, O75037, P62883, P62884, Q0V8F1, Q21624, Q25306, Q3TLR7, Q4V837, Q5EBE8, Q5RHI5, Q5ZJW8, Q6GPU3, Q6NWV3, Q6NYH1, Q6P1W0, Q7ZV55, Q8IZU2, Q9FNN2, Q9NZJ0, B8P4B0, G1SJB4, O42248, O42249, P63243, P63244, P63245, P63246, P63247, P68040, P87314, Q3MKM6, Q4R7Y4, Q75LV5, Q91WM3, Q93134

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
rRNA modification in the nucleus and cytosol	5	24.6×	2e-04
Major pathway of rRNA processing in the nucleolus and cytosol	10	16.2×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	7	28.0×	1e-06
rRNA processing	9	22.4×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2072 predictions. Top by Δscore:

Variant	Effect	Δscore
3:51933777:CCCAC:C	acceptor_gain	1.0000
3:51933778:CCAC:C	acceptor_gain	1.0000
3:51933778:CCACC:C	acceptor_gain	1.0000
3:51933779:CAC:C	acceptor_gain	1.0000
3:51933779:CACC:C	acceptor_gain	1.0000
3:51933783:T:A	acceptor_loss	1.0000
3:51934626:CCCA:C	donor_loss	1.0000
3:51934628:CA:C	donor_loss	1.0000
3:51934629:A:C	donor_loss	1.0000
3:51934772:CAGAG:C	acceptor_gain	1.0000
3:51934773:AGAG:A	acceptor_gain	1.0000
3:51934774:GAG:G	acceptor_gain	1.0000
3:51934775:AG:A	acceptor_gain	1.0000
3:51934775:AGC:A	acceptor_loss	1.0000
3:51934776:GCTAT:G	acceptor_loss	1.0000
3:51934777:C:CA	acceptor_loss	1.0000
3:51934777:C:CC	acceptor_gain	1.0000
3:51934779:A:AC	acceptor_gain	1.0000
3:51934779:A:C	acceptor_gain	1.0000
3:51934784:C:CT	acceptor_gain	1.0000
3:51934785:A:T	acceptor_gain	1.0000
3:51935191:TCTTA:T	donor_loss	1.0000
3:51935192:CTTAC:C	donor_loss	1.0000
3:51935193:TTA:T	donor_loss	1.0000
3:51935194:TA:T	donor_loss	1.0000
3:51935195:A:AC	donor_gain	1.0000
3:51935195:AC:A	donor_gain	1.0000
3:51935196:C:CC	donor_gain	1.0000
3:51935196:CC:C	donor_gain	1.0000
3:51935258:CC:C	acceptor_gain	1.0000

AlphaMissense

3081 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:51935626:A:G	W268R	1.000
3:51935626:A:T	W268R	1.000
3:51935654:G:C	S258R	1.000
3:51935654:G:T	S258R	1.000
3:51935656:T:G	S258R	1.000
3:51935385:A:G	W310R	0.999
3:51935385:A:T	W310R	0.999
3:51935417:G:T	T299K	0.999
3:51935624:C:A	W268C	0.999
3:51935624:C:G	W268C	0.999
3:51935640:C:G	R263P	0.999
3:51935649:G:A	S260F	0.999
3:51935650:A:G	S260P	0.999
3:51935661:A:G	L256P	0.999
3:51935661:A:T	L256H	0.999
3:51936348:G:T	A215D	0.999
3:51936432:A:G	L214P	0.999
3:51937192:A:G	W173R	0.999
3:51937192:A:T	W173R	0.999
3:51938128:C:G	A83P	0.999
3:51933587:C:A	W449C	0.998
3:51933587:C:G	W449C	0.998
3:51933589:A:G	W449R	0.998
3:51933589:A:T	W449R	0.998
3:51933721:C:A	G441W	0.998
3:51933773:A:C	F423L	0.998
3:51933773:A:T	F423L	0.998
3:51933775:A:G	F423L	0.998
3:51934763:A:G	W350R	0.998
3:51934763:A:T	W350R	0.998

dbSNP variants (sampled 300 via entrez): RS1000066535 (3:51933300 A>G), RS1000141923 (3:51933253 C>T), RS1001031386 (3:51940491 C>T), RS1001284292 (3:51938923 C>T), RS1001556641 (3:51943264 C>T), RS1001947692 (3:51937106 C>T), RS1002292665 (3:51942946 G>A,C,T), RS1002621762 (3:51939945 T>C), RS1002671818 (3:51940682 C>CA), RS1002715207 (3:51940290 G>A), RS1003061603 (3:51940926 C>G), RS1004396042 (3:51941749 C>T), RS1004460617 (3:51935578 C>T), RS1004766534 (3:51935328 G>A,C), RS1004900993 (3:51941197 A>G)

Disease associations

OMIM: gene MIM:620013 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression, affects expression, decreases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Estradiol	affects expression, increases expression	3
Arsenic Trioxide	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
cinobufagin	decreases expression	1
deoxynivalenol	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	decreases phosphorylation	1
nivalenol	increases expression	1
acetochlor	affects methylation, increases abundance	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
LDN 193189	affects cotreatment, decreases expression	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
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Herbicides	affects methylation, increases abundance	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Nickel	increases expression	1

Clinical trials (associated diseases)

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