UTP3

Summary

UTP3 (UTP3 small subunit processome component, HGNC:24477) is a protein-coding gene on chromosome 4q13.3, encoding Something about silencing protein 10 (Q9NQZ2). Essential for gene silencing: has a role in the structure of silenced chromatin. It is a selective cancer dependency (DepMap: 84.1% of cell lines).

Enables RNA binding activity. Involved in ribosomal small subunit biogenesis. Located in nucleolus. Part of small-subunit processome.

Source: NCBI Gene 57050 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• Cancer dependency (DepMap): dependent in 84.1% of screened cell lines
• MANE Select transcript: NM_020368

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24477
Approved symbol	UTP3
Name	UTP3 small subunit processome component
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23256, DKFZp761F222, SAS10, CRLZ1
Ensembl gene	ENSG00000132467
Ensembl biotype	protein_coding
OMIM	611614
Entrez	57050

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000254803

RefSeq mRNA: 1 — MANE Select: NM_020368 NM_020368

CCDS: CCDS3546

Canonical transcript exons

ENST00000254803 — 1 exons

Exon	Start	End
ENSE00000904388	70688532	70690551

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 93.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.2146 / max 407.4398, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47989	26.5782	1808
47990	0.6365	357

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parietal pleura	UBERON:0002400	93.85	gold quality
visceral pleura	UBERON:0002401	93.54	gold quality
parotid gland	UBERON:0001831	93.29	gold quality
tendon of biceps brachii	UBERON:0008188	93.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.05	gold quality
monocyte	CL:0000576	92.77	gold quality
pleura	UBERON:0000977	92.58	gold quality
mononuclear cell	CL:0000842	92.50	gold quality
islet of Langerhans	UBERON:0000006	92.47	gold quality
leukocyte	CL:0000738	92.46	gold quality
pylorus	UBERON:0001166	91.20	gold quality
colonic mucosa	UBERON:0000317	91.12	gold quality
spleen	UBERON:0002106	90.98	gold quality
lymph node	UBERON:0000029	90.59	gold quality
medial globus pallidus	UBERON:0002477	90.34	gold quality
granulocyte	CL:0000094	90.29	gold quality
lower lobe of lung	UBERON:0008949	90.25	gold quality
corpus epididymis	UBERON:0004359	90.14	gold quality
cauda epididymis	UBERON:0004360	90.06	gold quality
caput epididymis	UBERON:0004358	90.05	gold quality
germinal epithelium of ovary	UBERON:0001304	90.02	gold quality
mammary duct	UBERON:0001765	89.86	gold quality
superficial temporal artery	UBERON:0001614	89.70	gold quality
vermiform appendix	UBERON:0001154	89.58	gold quality
stromal cell of endometrium	CL:0002255	89.56	gold quality
cervix squamous epithelium	UBERON:0006922	89.44	gold quality
oral cavity	UBERON:0000167	89.42	gold quality
seminal vesicle	UBERON:0000998	89.35	gold quality
mucosa of urinary bladder	UBERON:0001259	89.28	gold quality
thymus	UBERON:0002370	89.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.93
E-MTAB-6524	no	157.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): LEF1

miRNA regulators (miRDB)

48 targeting UTP3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130B-5P	99.83	68.50	1888

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• A strong promoter activity of pre-B cell stage-specific Crlz1 gene is caused by one distal LEF-1 and multiple proximal Ets sites. (PMID:21544627)
• The ATR checkpoint pathway causes a histone chaperone normally associated with the replication fork, ASF1a, to degrade through a CRL1(betaTRCP)-dependent ubiquitination/proteasome pathway, leading to the localized dechromatinization and gene repression. (PMID:24700029)
• Sas10 is essential not only for delivering the Mpp10-Imp3-Imp4 complex to the nucleolus for assembling the SSU processome but also for fine-tuning Mpp10 turnover in the nucleolus during organogenesis. (PMID:30773582)
• Crlz-1, which is induced by canonical Wnt/beta-catenin signaling, controls Germinal Center reaction by regulating the expression of Bcl-6 in centroblasts. (PMID:31586036)
• HCP5 prevents ubiquitination-mediated UTP3 degradation to inhibit apoptosis by activating c-Myc transcriptional activity. (PMID:36245126)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	utp3	ENSDARG00000056720
mus_musculus	Utp3	ENSMUSG00000070697
rattus_norvegicus	Utp3	ENSRNOG00000080476
drosophila_melanogaster	Sas10	FBGN0029755

Paralogs (1): NGDN (ENSG00000129460)

Protein

Protein identifiers

Something about silencing protein 10 — Q9NQZ2 (reviewed: Q9NQZ2)

Alternative names: Charged amino acid-rich leucine zipper 1, Disrupter of silencing SAS10, UTP3 homolog

All UniProt accessions (1): Q9NQZ2

UniProt curated annotations — full annotation on UniProt →

Function. Essential for gene silencing: has a role in the structure of silenced chromatin. Plays a role in the developing brain. 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. 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. Citrullinated by PADI4.

Similarity. Belongs to the SAS10 family.

RefSeq proteins (1): NP_065101* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007146	Sas10/Utp3/C1D	Family
IPR018972	Sas10_C_dom	Domain

Pfam: PF04000, PF09368

UniProt features (21 total): modified residue 8, compositionally biased region 6, region of interest 3, chain 1, cross-link 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQZ2-F1	69.50	0.17

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 (9): 8, 37, 144, 150, 362, 365, 368, 385, 144

Function

Pathways and Gene Ontology

Reactome pathways

5 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
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 197 (showing top): GOBP_RIBOSOME_BIOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, chr4q13, PUJANA_CHEK2_PCC_NETWORK, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GNF2_FBL, GARY_CD5_TARGETS_DN, KIM_GERMINAL_CENTER_T_HELPER_UP, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_HEAD_DEVELOPMENT, ACEVEDO_LIVER_CANCER_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (4): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), chromatin organization (GO:0006325), brain development (GO:0007420), ribosomal small subunit biogenesis (GO:0042274)

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

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), small-subunit processome (GO:0032040)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
maturation of SSU-rRNA	1
cellular component organization	1
central nervous system development	1
animal organ development	1
head development	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

2259 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UTP3	JCHAIN	P01591	923
UTP3	UTP18	Q9Y5J1	833
UTP3	UTP11	Q9Y3A2	833
UTP3	LAP3	P28838	818
UTP3	WDR46	O15213	814
UTP3	FCF1	Q9Y324	804
UTP3	UTP14A	Q9BVJ6	785
UTP3	DNTTIP2	Q5QJE6	770
UTP3	RRP36	Q96EU6	768
UTP3	C1D	Q13901	768
UTP3	UTP6	Q9NYH9	752
UTP3	UTP25	Q68CQ4	744
UTP3	WDR36	Q8NI36	744
UTP3	CBFB	Q13951	727
UTP3	PWP2	Q15269	714

IntAct

147 interactions, top by confidence:

A	B	Type	Score
IMP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.670
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
DVL3	UTP3	psi-mi:“MI:0915”(physical association)	0.560
UTP3	CDCA7L	psi-mi:“MI:0915”(physical association)	0.560
UTP3	DVL3	psi-mi:“MI:0915”(physical association)	0.560
CDCA7L	UTP3	psi-mi:“MI:0915”(physical association)	0.560
UTP3	H1-4	psi-mi:“MI:0915”(physical association)	0.560
UTP3	H1-1	psi-mi:“MI:0915”(physical association)	0.560
CEP70	UTP3	psi-mi:“MI:0915”(physical association)	0.560
UTP3	PICK1	psi-mi:“MI:0915”(physical association)	0.560
C1orf131	UTP3	psi-mi:“MI:0915”(physical association)	0.560
UTP3	HNRNPC	psi-mi:“MI:0915”(physical association)	0.540
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	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
UTP3	TF	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530

BioGRID (198): UTP3 (Two-hybrid), UTP3 (Two-hybrid), UTP3 (Affinity Capture-MS), UTP3 (Affinity Capture-MS), TF (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), CTNNA2 (Affinity Capture-MS), IMP3 (Co-fractionation), IMP4 (Co-fractionation), MPHOSPH10 (Co-fractionation), UTP3 (Co-fractionation), UTP3 (Co-fractionation), UTP3 (Co-fractionation), UTP3 (Affinity Capture-RNA), UTP3 (Affinity Capture-MS)

ESM2 similar proteins: A7TQN2, O00566, O13910, O36018, O42877, O43088, O74517, O94693, P34078, P40546, P42846, P47083, P53952, P87137, Q02554, Q04347, Q04500, Q05021, Q06631, Q08287, Q08492, Q09713, Q09799, Q10183, Q10191, Q12035, Q12136, Q1MTS0, Q23525, Q2VPH1, Q4KLV7, Q6CKH1, Q6CTS8, Q6CU86, Q6DRJ4, Q6FSD4, Q7KN79, Q810V0, Q8L3P4, Q9FJY5

Diamond homologs: Q12136, Q1MTS0, Q6AXX4, Q9I7W5, Q9JI13, Q9NQZ2, Q09713, Q28IV8, Q2KII6, Q4KLC4, Q5M985, Q6PFJ1, Q8L3P4, Q8NEJ9, Q9DB96

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MPHOSPH10	“up-regulates activity”	UTP3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	5	35.7×	2e-06
Eukaryotic Translation Initiation	9	29.6×	3e-10
Cap-dependent Translation Initiation	9	29.6×	3e-10
SARS-CoV-1 modulates host translation machinery	9	29.6×	3e-10
Peptide chain elongation	20	27.0×	9e-22
Viral mRNA Translation	20	27.0×	9e-22
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	20	26.7×	9e-22
Eukaryotic Translation Elongation	9	26.7×	6e-10

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	5	46.0×	6e-06
chromosome condensation	6	41.4×	6e-07
cytoplasmic translation	21	31.9×	2e-23
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	5	27.6×	9e-05
ribosomal small subunit biogenesis	12	22.4×	3e-11
rRNA processing	16	18.6×	7e-14
translation	22	18.5×	2e-19
ribosomal large subunit biogenesis	5	18.2×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

10 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70688563:G:GA	donor_gain	0.2300
4:70689506:TCG:T	acceptor_gain	0.2300
4:70688820:T:TA	donor_gain	0.2200
4:70688821:A:AA	donor_gain	0.2200
4:70688628:C:A	donor_gain	0.2100
4:70689395:GT:G	donor_gain	0.2100
4:70689396:T:G	donor_gain	0.2100
4:70689396:TT:T	donor_gain	0.2100
4:70689665:G:GT	donor_gain	0.2100
4:70688626:G:GG	donor_gain	0.2000

AlphaMissense

3127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:70689952:A:C	R425S	0.997
4:70689952:A:T	R425S	0.997
4:70690004:G:C	A443P	0.997
4:70689064:G:C	W129C	0.996
4:70689064:G:T	W129C	0.996
4:70689966:G:C	R430P	0.996
4:70689970:T:A	N431K	0.995
4:70689970:T:G	N431K	0.995
4:70689976:A:C	R433S	0.995
4:70689976:A:T	R433S	0.995
4:70689939:T:C	L421P	0.994
4:70689951:G:C	R425T	0.994
4:70689988:A:C	R437S	0.994
4:70689988:A:T	R437S	0.994
4:70689995:T:C	F440L	0.994
4:70689997:C:A	F440L	0.994
4:70689997:C:G	F440L	0.994
4:70689062:T:A	W129R	0.993
4:70689062:T:C	W129R	0.993
4:70689489:T:C	L271P	0.993
4:70689904:A:C	R409S	0.993
4:70689904:A:T	R409S	0.993
4:70690018:A:C	R447S	0.993
4:70690018:A:T	R447S	0.993
4:70689923:G:C	A416P	0.992
4:70689975:G:C	R433T	0.992
4:70690100:A:C	S475R	0.992
4:70690102:C:A	S475R	0.992
4:70690102:C:G	S475R	0.992
4:70689170:G:C	A165P	0.991

dbSNP variants (sampled 300 via entrez): RS1001791571 (4:70686531 A>C), RS1001866855 (4:70686869 T>A), RS1002459236 (4:70689549 C>T), RS1003537900 (4:70688307 C>A,G,T), RS1004188610 (4:70690441 G>A), RS1004895991 (4:70690929 G>C), RS1005837451 (4:70687953 C>G), RS1007438246 (4:70689085 C>T), RS1008696651 (4:70690952 G>A), RS1009881590 (4:70686923 T>C), RS1011295101 (4:70688623 G>A), RS1011571259 (4:70689555 A>G), RS1011791875 (4:70688161 C>T), RS1012001776 (4:70688973 G>A,C,T), RS1013666838 (4:70687453 T>A)

Disease associations

OMIM: gene MIM:611614 | 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
GCST005163_1	Glucagon levels in response to oral glucose tolerance test (120 minutes)	7.000000e-06
GCST009240_399	Serum metabolite levels (CMS)	8.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004307	glucose tolerance test
EFO:0008463	glucagon measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
deoxynivalenol	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Irinotecan	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Adenine	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Vehicle Emissions	decreases expression	1
Cadmium	increases abundance, increases expression	1
Colchicine	decreases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Etoposide	decreases expression	1
Fluorouracil	affects cotreatment, increases expression	1
Hydroxyurea	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1

Clinical trials (associated diseases)

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