IMP3

Summary

IMP3 (IMP U3 small nucleolar ribonucleoprotein 3, HGNC:14497) is a protein-coding gene on chromosome 15q24.2, encoding U3 small nucleolar ribonucleoprotein protein IMP3 (Q9NV31). Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). It is a common-essential gene (DepMap: required in 98.6% of cancer cell lines).

This gene encodes the human homolog of the yeast Imp3 protein. The protein localizes to the nucleoli and interacts with the U3 snoRNP complex. The protein contains an S4 domain.

Source: NCBI Gene 55272 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 98.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_018285

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14497
Approved symbol	IMP3
Name	IMP U3 small nucleolar ribonucleoprotein 3
Location	15q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10968, BRMS2
Ensembl gene	ENSG00000177971
Ensembl biotype	protein_coding
OMIM	612980
Entrez	55272

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000314852, ENST00000403490, ENST00000565349

RefSeq mRNA: 1 — MANE Select: NM_018285 NM_018285

CCDS: CCDS10282

Canonical transcript exons

ENST00000403490 — 1 exons

Exon	Start	End
ENSE00001556046	75639093	75640224

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 96.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.5535 / max 204.0305, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150995	45.8798	1821
150996	2.6737	1411

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.09	gold quality
granulocyte	CL:0000094	96.03	gold quality
skin of abdomen	UBERON:0001416	94.95	gold quality
right lobe of liver	UBERON:0001114	94.83	gold quality
right adrenal gland	UBERON:0001233	94.76	gold quality
right adrenal gland cortex	UBERON:0035827	94.73	gold quality
left adrenal gland	UBERON:0001234	94.60	gold quality
esophagus mucosa	UBERON:0002469	94.58	gold quality
left adrenal gland cortex	UBERON:0035825	94.55	gold quality
skin of leg	UBERON:0001511	94.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.37	gold quality
adrenal cortex	UBERON:0001235	94.10	gold quality
zone of skin	UBERON:0000014	94.05	gold quality
lower esophagus mucosa	UBERON:0035834	94.05	gold quality
spleen	UBERON:0002106	94.02	gold quality
gastrocnemius	UBERON:0001388	93.93	gold quality
apex of heart	UBERON:0002098	93.83	gold quality
muscle of leg	UBERON:0001383	93.68	gold quality
nipple	UBERON:0002030	93.68	gold quality
cerebellar vermis	UBERON:0004720	93.64	gold quality
anterior cingulate cortex	UBERON:0009835	93.50	gold quality
body of stomach	UBERON:0001161	93.47	gold quality
cingulate cortex	UBERON:0003027	93.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.38	gold quality
pharyngeal mucosa	UBERON:0000355	93.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.24	gold quality
adrenal gland	UBERON:0002369	93.22	gold quality
right frontal lobe	UBERON:0002810	93.19	gold quality
upper arm skin	UBERON:0004263	93.03	gold quality
adult organism	UBERON:0007023	93.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2

miRNA regulators (miRDB)

27 targeting IMP3, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-495-5P	97.62	68.28	682
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-4444	92.67	67.92	56

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• The expression of ribonuclear protein IMP3 in laryngeal carcinogenesis. (PMID:32370989)
• Correlations of expressions of IMP3 and VEGF with stage of osteosarcoma, microvascular density and pulmonary metastasis. (PMID:33277867)
• RNA-binding protein IMP3 is a novel regulator of MEK1/ERK signaling pathway in the progression of colorectal Cancer through the stabilization of MEKK1 mRNA. (PMID:34154626)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	imp3	ENSDARG00000115266
mus_musculus	Imp3	ENSMUSG00000032288
drosophila_melanogaster	CG4866	FBGN0034232
caenorhabditis_elegans	C48B6.2	WBGENE00016740

Protein

Protein identifiers

U3 small nucleolar ribonucleoprotein protein IMP3 — Q9NV31 (reviewed: Q9NV31)

Alternative names: BRMS2

All UniProt accessions (1): Q9NV31

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. 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. Component of a heterotrimeric complex containing IMP3, IMP4 and MPHOSPH10. Interacts with MPHOSPH10.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the universal ribosomal protein uS4 family.

RefSeq proteins (1): NP_060755* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001912	Ribosomal_uS4_N	Domain
IPR002942	S4_RNA-bd	Domain
IPR022801	Ribosomal_uS4	Family
IPR036986	S4_RNA-bd_sf	Homologous_superfamily

Pfam: PF00163, PF01479

UniProt features (11 total): strand 5, helix 3, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87
2CQJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NV31-F1	90.72	0.77

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: 158 (showing top): GOBP_RIBOSOME_BIOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MODULE_151, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, RYTTCCTG_ETS2_B, HU_GENOTOXIC_DAMAGE_24HR, DBP_Q6, CHNG_MULTIPLE_MYELOMA_HYPERPLOID_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_MAGENTA_DN, MODULE_114, REACTOME_METABOLISM_OF_RNA

GO Biological Process (4): rRNA processing (GO:0006364), maturation of SSU-rRNA (GO:0030490), ribosomal small subunit biogenesis (GO:0042274), ribosome biogenesis (GO:0042254)

GO Molecular Function (4): RNA binding (GO:0003723), rRNA binding (GO:0019843), snoRNA binding (GO:0030515), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), preribosome (GO:0030684), small-subunit processome (GO:0032040), Mpp10 complex (GO:0034457), ribonucleoprotein complex (GO:1990904)

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
ribosome biogenesis	2
ribonucleoprotein complex biogenesis	2
RNA binding	2
nuclear lumen	2
cellular anatomical structure	2
nucleolus	2
nuclear protein-containing complex	2
RNA processing	1
rRNA metabolic process	1
rRNA processing	1
ribosomal small subunit biogenesis	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
ribonucleoprotein complex	1
preribosome	1
t-UTP complex	1
90S preribosome	1
protein-containing complex	1

Protein interactions and networks

STRING

4323 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IMP3	FUBP3	Q96I24	495
IMP3	XRN2	Q9H0D6	445
IMP3	PTGDR	Q13258	434
IMP3	MATR3	P43243	426
IMP3	IGF2BP2	Q9Y6M1	425
IMP3	MRPS7	Q9Y2R9	418
IMP3	RPL11	P25121	415
IMP3	ADAM9	Q13443	412
IMP3	ATF4	P18848	387
IMP3	R3HCC1	Q9Y3T6	373
IMP3	ATM	Q13315	363
IMP3	EPRS1	P07814	353
IMP3	YARS1	P54577	353
IMP3	IMP4	Q96G21	352
IMP3	VARS1	P26640	352

IntAct

133 interactions, top by confidence:

A	B	Type	Score
IMP3	ZYX	psi-mi:“MI:0915”(physical association)	0.830
ZYX	IMP3	psi-mi:“MI:0915”(physical association)	0.830
IMP3	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.760
CCNDBP1	IMP3	psi-mi:“MI:0915”(physical association)	0.760
USHBP1	IMP3	psi-mi:“MI:0915”(physical association)	0.720
IMP3	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
IMP3	TFIP11	psi-mi:“MI:0915”(physical association)	0.670
TFIP11	IMP3	psi-mi:“MI:0915”(physical association)	0.670
MCC	IMP3	psi-mi:“MI:0915”(physical association)	0.670
IMP3	MPHOSPH10	psi-mi:“MI:0915”(physical association)	0.670
IMP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.670
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NOL9	SENP3	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
KLC3	IMP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (164): IMP3 (Two-hybrid), IMP3 (Two-hybrid), IMP3 (Two-hybrid), USHBP1 (Two-hybrid), KLC3 (Two-hybrid), IMP3 (Affinity Capture-MS), IMP3 (Affinity Capture-MS), IMP3 (Affinity Capture-MS), IMP3 (Affinity Capture-MS), IMP3 (Affinity Capture-MS), IMP3 (Affinity Capture-MS), IMP3 (Two-hybrid), IMP3 (Co-fractionation), IMP3 (Co-fractionation), IMP3 (Co-fractionation)

ESM2 similar proteins: A0A1D8PGY8, A0B9L2, A2SSV9, A3CWH7, A4FWL4, A6QLG5, A6UPW5, A6UW05, A6VGQ7, A7IAH7, A9A9Z3, A9L913, B7NZS8, B8GEG7, G0S488, O01513, O13516, O13835, O15612, O61078, P05755, P12531, P14132, P17959, P27570, P29314, P30190, P32899, P46781, P52810, Q01688, Q0W1V5, Q12ZR5, Q20228, Q25555, Q2FT97, Q3T0M3, Q46GC8, Q6KZP7, Q6LXN0

Diamond homologs: A0A1D8PGY8, A0AJ45, A0B9L2, A0RY02, A1RT03, A1RWT8, A2BK77, A2SSV9, A3CWH7, A3DMQ4, A3MUS9, A4FWL4, A4WM27, A4YIN4, A5UN53, A6QLG5, A6UPW5, A6UW05, A6VGQ7, A7IAH7, A8A8W3, A8MDS5, A9A436, A9A9Z3, A9HL98, A9L913, B0R4Y0, B1L795, B1Y9B8, B4PEU8, B6YSQ1, B7NZS8, B8D0T6, B8DHE5, B8GEG7, C1CXD5, C1KVP3, C3MJP5, C3MZ03, C3N052

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MPHOSPH10	“up-regulates activity”	IMP3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 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	9	20.8×	1e-08
Viral mRNA Translation	9	20.8×	1e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	9	20.5×	1e-08
rRNA processing in the nucleus and cytosol	7	20.5×	7e-07
Formation of a pool of free 40S subunits	10	20.4×	5e-09
Selenocysteine synthesis	9	19.7×	2e-08
Eukaryotic Translation Termination	9	19.7×	2e-08
Formation of the ternary complex, and subsequently, the 43S complex	5	19.6×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal large subunit biogenesis	6	30.2×	5e-06
cytoplasmic translation	11	23.1×	7e-10
ribosomal small subunit biogenesis	7	18.1×	1e-05
rRNA processing	9	14.5×	2e-06
regulation of alternative mRNA splicing, via spliceosome	5	13.9×	2e-03
translation	10	11.7×	2e-06
mRNA processing	7	6.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

802 predictions. Top by Δscore:

Variant	Effect	Δscore
15:75647437:C:CA	donor_gain	0.9900
15:75647886:T:TA	donor_gain	0.9900
15:75647902:T:TA	donor_gain	0.9900
15:75647903:C:A	donor_gain	0.9900
15:75648098:T:G	donor_gain	0.9900
15:75647865:C:A	donor_gain	0.9800
15:75647866:C:A	donor_gain	0.9800
15:75647864:T:TA	donor_gain	0.9700
15:75648310:T:TA	donor_gain	0.9700
15:75648423:AGT:A	donor_gain	0.9700
15:75647882:T:TA	donor_gain	0.9600
15:75648102:GTGT:G	donor_gain	0.9600
15:75648265:G:C	donor_gain	0.9600
15:75647434:A:AC	donor_gain	0.9500
15:75647435:C:CC	donor_gain	0.9500
15:75647912:G:A	donor_gain	0.9500
15:75648082:T:A	donor_gain	0.9500
15:75648133:GGGTC:G	donor_gain	0.9500
15:75648134:GGTCG:G	donor_gain	0.9500
15:75648335:T:TA	donor_gain	0.9500
15:75647072:C:A	donor_gain	0.9400
15:75647376:T:TA	donor_gain	0.9400
15:75647424:T:A	donor_gain	0.9400
15:75647897:C:CT	donor_gain	0.9400
15:75647898:C:CT	donor_gain	0.9400
15:75648079:CT:C	donor_gain	0.9400
15:75648437:C:A	acceptor_gain	0.9400
15:75640267:CC:C	acceptor_gain	0.9300
15:75640268:CC:C	acceptor_gain	0.9300
15:75641536:A:AC	donor_gain	0.9300

AlphaMissense

1179 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:75639691:A:G	W160R	0.999
15:75639691:A:T	W160R	0.999
15:75639696:A:T	V158D	0.999
15:75639689:C:A	W160C	0.998
15:75639689:C:G	W160C	0.998
15:75639720:A:T	V150D	0.998
15:75639837:A:T	L111H	0.997
15:75639678:G:A	S164F	0.996
15:75639848:G:C	C107W	0.996
15:75640142:C:A	E9D	0.996
15:75640142:C:G	E9D	0.996
15:75639867:A:T	V101D	0.995
15:75639703:C:G	D156H	0.994
15:75639753:C:T	G139D	0.994
15:75639762:A:T	V136E	0.994
15:75639844:G:T	R109S	0.994
15:75639861:G:T	A103D	0.994
15:75639629:G:C	F180L	0.993
15:75639629:G:T	F180L	0.993
15:75639631:A:G	F180L	0.993
15:75639754:C:G	G139R	0.993
15:75639769:C:A	G134W	0.993
15:75639849:C:T	C107Y	0.993
15:75639850:A:G	C107R	0.993
15:75639852:A:G	F106S	0.993
15:75639678:G:T	S164Y	0.991
15:75639690:C:G	W160S	0.991
15:75639741:A:T	V143D	0.991
15:75639777:A:T	V131E	0.991
15:75639789:G:T	A127D	0.991

dbSNP variants (sampled 300 via entrez): RS1000768870 (15:75640648 T>C), RS1000820280 (15:75640418 C>T), RS1002401725 (15:75641284 C>T), RS1005525448 (15:75641097 C>T), RS1005787054 (15:75640743 T>C), RS1006119357 (15:75639531 A>G), RS1006624670 (15:75641903 T>C), RS1006969279 (15:75640186 C>A,G,T), RS1007086558 (15:75641539 A>G,T), RS1007307645 (15:75638875 A>G), RS1008043193 (15:75640384 G>A,C), RS1008632955 (15:75639241 G>A), RS1009103445 (15:75638982 C>A), RS1009538726 (15:75640401 A>C), RS1009695411 (15:75640619 A>G)

Disease associations

OMIM: gene MIM:612980 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): SIN3A-related intellectual disability syndrome due to a point mutation (MONDO:0044700)

Orphanet (2): SIN3-related intellectual disability syndrome due to a point mutation (Orphanet:500166), 15q24 microdeletion syndrome (Orphanet:94065)

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Cadmium Chloride	decreases expression, increases methylation, increases expression	3
Formaldehyde	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
abrine	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Atrazine	decreases expression	1
Cadmium	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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