NOL7

Summary

NOL7 (nucleolar protein 7, HGNC:21040) is a protein-coding gene on chromosome 6p23, encoding U3 small nucleolar RNA-associated protein NOL7 (Q9UMY1). Functions as part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit that coordinates the first two steps of ribosome biogenesis in transcription of the primary transcript pre-RNA and pre-18S processing. It is a selective cancer dependency (DepMap: 81.7% of cell lines).

The protein encoded by this gene localizes to the nucleolus, where it maintains nucleolar structure and cell growth rates. The encoded protein also functions as a tumor suppressor and regulator of angiogenesis. The RB tumor suppressor gene recruits transcription factors to this gene and positively regulates its expression. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 51406 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 73 total
• Cancer dependency (DepMap): dependent in 81.7% of screened cell lines
• MANE Select transcript: NM_016167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21040
Approved symbol	NOL7
Name	nucleolar protein 7
Location	6p23
Locus type	gene with protein product
Status	Approved
Aliases	NOP27, RARG-1, dJ223E5.2
Ensembl gene	ENSG00000225921
Ensembl biotype	protein_coding
OMIM	611533
Entrez	51406

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000420088, ENST00000451315, ENST00000474485, ENST00000865196, ENST00000865197

RefSeq mRNA: 2 — MANE Select: NM_016167 NM_001317724, NM_016167

CCDS: CCDS4528

Canonical transcript exons

ENST00000451315 — 8 exons

Exon	Start	End
ENSE00001168711	13615335	13615624
ENSE00001799965	13620754	13621712
ENSE00003491578	13618058	13618139
ENSE00003508517	13620208	13620329
ENSE00003509880	13616463	13616521
ENSE00003592387	13620408	13620485
ENSE00003651398	13615712	13615772
ENSE00003661006	13617770	13617801

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 138.3844 / max 1725.4780, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65955	138.3844	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.77	gold quality
pancreatic ductal cell	CL:0002079	98.39	gold quality
tendon of biceps brachii	UBERON:0008188	98.02	gold quality
epithelium of nasopharynx	UBERON:0001951	97.72	gold quality
heart right ventricle	UBERON:0002080	97.21	gold quality
tendon	UBERON:0000043	97.05	gold quality
epithelial cell of pancreas	CL:0000083	96.98	gold quality
bronchial epithelial cell	CL:0002328	96.92	gold quality
nephron tubule	UBERON:0001231	96.67	gold quality
cervix squamous epithelium	UBERON:0006922	96.67	gold quality
calcaneal tendon	UBERON:0003701	96.64	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.51	gold quality
myocardium	UBERON:0002349	96.44	gold quality
superficial temporal artery	UBERON:0001614	96.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.36	gold quality
germinal epithelium of ovary	UBERON:0001304	96.34	gold quality
synovial joint	UBERON:0002217	96.34	gold quality
colonic mucosa	UBERON:0000317	96.28	gold quality
substantia nigra pars compacta	UBERON:0001965	96.27	gold quality
epithelium of bronchus	UBERON:0002031	96.25	gold quality
adult organism	UBERON:0007023	96.24	gold quality
olfactory bulb	UBERON:0002264	96.23	gold quality
bronchus	UBERON:0002185	96.22	gold quality
pylorus	UBERON:0001166	96.19	gold quality
pons	UBERON:0000988	96.15	gold quality
nasal cavity mucosa	UBERON:0001826	96.12	gold quality
vena cava	UBERON:0004087	96.11	gold quality
mammary duct	UBERON:0001765	96.08	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.05	gold quality
type B pancreatic cell	CL:0000169	96.00	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, RXRA, SP1

miRNA regulators (miRDB)

90 targeting NOL7, 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-656-3P	100.00	72.15	2788
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 81.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• determined that the essential elements required for the optimal promoter activity of NOL7 were 560 bp upstream of its translation start site. (PMID:20206243)
• Three alternatively spliced forms of the human NOL7 gene coding for relatively small proteins were identified (PMID:21818416)
• NOL7 is the legitimate tumor suppressor gene located on 6p23. (PMID:22123719)
• NOL7 significantly alters TSP-1 expression and may be a master regulator that coordinates the post-transcriptional expression of key signaling factors critical for the regulation of the angiogenic phenotype. (PMID:23085760)
• NOL7 facilitates melanoma progression and metastasis. (PMID:34642294)
• Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing. (PMID:37246770)
• PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation. (PMID:39103492)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nol7	ENSDARG00000075795
mus_musculus	Nol7	ENSMUSG00000063200
rattus_norvegicus	Nol7	ENSRNOG00000017904

Protein

Protein identifiers

U3 small nucleolar RNA-associated protein NOL7 — Q9UMY1 (reviewed: Q9UMY1)

Alternative names: Nucleolar protein 7, Nucleolar protein of 27 kDa

All UniProt accessions (2): H7C2B1, Q9UMY1

UniProt curated annotations — full annotation on UniProt →

Function. Functions as part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit that coordinates the first two steps of ribosome biogenesis in transcription of the primary transcript pre-RNA and pre-18S processing. 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. This subunit is required for processing of the 5’-external transcribed spacer sequence (5’ETS) of the primary transcript pre-rRNA to yield the 18S rRNA. Also plays a role in maintaining early pre-rRNA levels, either by assisting in its transcription or stability.

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.

Tissue specificity. Expressed in numerous tissues. Particularly prevalent in the adrenal gland, thyroid gland, heart and skeletal muscle.

Similarity. Belongs to the UTP16 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UMY1-1	1	yes
Q9UMY1-2	2

RefSeq proteins (2): NP_001304653, NP_057251* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012579	NOL7_C	Domain

Pfam: PF08157

UniProt features (14 total): compositionally biased region 4, splice variant 2, sequence conflict 2, cross-link 2, chain 1, region of interest 1, coiled-coil region 1, modified residue 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-Q9UMY1-F1	72.02	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 (3): 133, 131, 162

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_RIBOSOME_BIOGENESIS, MODULE_255, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, MODULE_317, WANG_LMO4_TARGETS_DN, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, MODULE_480, GNF2_FBL, GNF2_ST13, BURTON_ADIPOGENESIS_10, ACEVEDO_LIVER_CANCER_UP, DANG_BOUND_BY_MYC, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (3): maturation of SSU-rRNA (GO:0030490), ribosomal small subunit biogenesis (GO:0042274), ribosome biogenesis (GO:0042254)

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

GO Cellular Component (5): chromosome (GO:0005694), nucleolus (GO:0005730), mitochondrion (GO:0005739), small-subunit processome (GO:0032040), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoprotein complex biogenesis	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
rRNA processing	1
ribosomal small subunit biogenesis	1
ribosome biogenesis	1
nucleic acid binding	1
binding	1
nuclear lumen	1
cytoplasm	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOL7	PECAM1	P16284	685
NOL7	THBS1	P07996	610
NOL7	CNOT10	Q9H9A5	606
NOL7	MTMR14	Q8NCE2	574
NOL7	ARMH3	Q5T2E6	562
NOL7	AMMECR1L	Q6DCA0	543
NOL7	NUBP1	P53384	497
NOL7	SLC4A1AP	Q9BWU0	487
NOL7	BCCIP	Q9P287	479
NOL7	PRPF38A	Q8NAV1	470
NOL7	ZKSCAN5	Q9Y2L8	465
NOL7	GPATCH3	Q96I76	463
NOL7	PQBP1	O60828	462
NOL7	TMUB2	Q71RG4	451
NOL7	DDX50	Q9BQ39	449

IntAct

48 interactions, top by confidence:

A	B	Type	Score
NOL7	WDR43	psi-mi:“MI:0914”(association)	0.640
CCNDBP1	NOL7	psi-mi:“MI:0915”(physical association)	0.560
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
NOL7	IPO5	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
PURG	U2SURP	psi-mi:“MI:0914”(association)	0.530
NOL7	VDAC1	psi-mi:“MI:0915”(physical association)	0.400
NOL7	PDCD11	psi-mi:“MI:0915”(physical association)	0.400
NOL7	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
NOL7	C8orf33	psi-mi:“MI:0915”(physical association)	0.370
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
KIF11	MAP4	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
NOL7	IPO5	psi-mi:“MI:0914”(association)	0.350
ITSN2	SNRPB2	psi-mi:“MI:0914”(association)	0.350
ARHGEF19	NUP42	psi-mi:“MI:0914”(association)	0.350
NPM3	KPNA3	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
CLEC4G	ARPC1B	psi-mi:“MI:0914”(association)	0.350
FBL	SHTN1	psi-mi:“MI:0914”(association)	0.350
IPO5	C11orf98	psi-mi:“MI:0914”(association)	0.350
RAB11A	SCAMP1	psi-mi:“MI:0914”(association)	0.350
RACK1	RPS3A	psi-mi:“MI:0914”(association)	0.350
SRP9	RPS3A	psi-mi:“MI:0914”(association)	0.350
	LAMA5	psi-mi:“MI:0914”(association)	0.350
C1orf174	POLRMT	psi-mi:“MI:0914”(association)	0.350
H1-6	RIOK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): NOL7 (Affinity Capture-MS), NOL7 (Affinity Capture-MS), NOL7 (Reconstituted Complex), NOL7 (Affinity Capture-MS), NOL7 (Affinity Capture-MS), WDR75 (Affinity Capture-MS), CEP120 (Affinity Capture-MS), UTP15 (Affinity Capture-MS), WDR43 (Affinity Capture-MS), CIRH1A (Affinity Capture-MS), NOL11 (Affinity Capture-MS), NOL7 (Affinity Capture-MS), IPO5 (Affinity Capture-MS), NOL7 (Affinity Capture-MS), NOL7 (Affinity Capture-MS)

ESM2 similar proteins: A5PJN1, O57594, O75683, P0DPK0, P53352, P70279, Q05B65, Q0VCY3, Q17QR4, Q2KIV0, Q2TBX7, Q3KRF3, Q3U155, Q3ZCI6, Q58CQ0, Q5D1Z3, Q5NVE2, Q5R939, Q5RGP9, Q5XIB5, Q5XIG5, Q5ZIH9, Q5ZMG5, Q640V3, Q641W3, Q66H19, Q6NS45, Q6PK04, Q7ZWE7, Q8BG17, Q8BK35, Q8C6C7, Q8CIL4, Q8NDD1, Q8NEF9, Q8R0K4, Q8R2N0, Q8TF30, Q96J88, Q9CR02

Diamond homologs: Q9D7Z3, Q9UMY1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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	6	23.9×	1e-05
Influenza Viral RNA Transcription and Replication	5	22.9×	5e-05
Influenza Infection	6	22.4×	1e-05
rRNA processing in the nucleus and cytosol	6	20.5×	2e-05
rRNA processing	6	18.7×	3e-05
Cellular response to starvation	5	17.6×	1e-04
Response of EIF2AK4 (GCN2) to amino acid deficiency	7	16.5×	1e-05
Peptide chain elongation	6	16.2×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	6	23.2×	4e-05
cytoplasmic translation	7	22.0×	1e-05
rRNA processing	6	14.4×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1543 predictions. Top by Δscore:

Variant	Effect	Δscore
6:13615581:G:GT	donor_gain	1.0000
6:13615769:GAAG:G	donor_gain	1.0000
6:13615770:AAGG:A	donor_loss	1.0000
6:13615773:G:GA	donor_loss	1.0000
6:13616458:A:AG	acceptor_gain	1.0000
6:13618056:A:AG	acceptor_gain	1.0000
6:13618057:G:GG	acceptor_gain	1.0000
6:13618057:GTT:G	acceptor_gain	1.0000
6:13618057:GTTA:G	acceptor_gain	1.0000
6:13618057:GTTAA:G	acceptor_gain	1.0000
6:13618136:TCAGG:T	donor_loss	1.0000
6:13618137:CAGG:C	donor_loss	1.0000
6:13618138:AG:A	donor_loss	1.0000
6:13618139:GGT:G	donor_loss	1.0000
6:13618140:GTA:G	donor_loss	1.0000
6:13618141:T:G	donor_loss	1.0000
6:13619756:A:AG	donor_gain	1.0000
6:13620406:A:AG	acceptor_gain	1.0000
6:13620407:G:GA	acceptor_gain	1.0000
6:13620407:GTAA:G	acceptor_gain	1.0000
6:13625647:ACTT:A	donor_loss	1.0000
6:13625648:CTT:C	donor_loss	1.0000
6:13625649:TTACC:T	donor_loss	1.0000
6:13625650:TA:T	donor_loss	1.0000
6:13625651:A:AC	donor_gain	1.0000
6:13625652:C:CC	donor_gain	1.0000
6:13632365:TTCA:T	donor_loss	1.0000
6:13632366:TCACC:T	donor_loss	1.0000
6:13632367:CA:C	donor_loss	1.0000
6:13632368:A:C	donor_loss	1.0000

AlphaMissense

1680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:13615739:G:C	R98S	0.994
6:13615739:G:T	R98S	0.994
6:13620467:T:C	F228L	0.994
6:13620469:T:A	F228L	0.994
6:13620469:T:G	F228L	0.994
6:13620322:G:C	R205S	0.993
6:13620322:G:T	R205S	0.993
6:13615758:T:C	F105L	0.991
6:13615760:C:A	F105L	0.991
6:13615760:C:G	F105L	0.991
6:13615563:T:C	F69L	0.990
6:13615565:C:A	F69L	0.990
6:13615565:C:G	F69L	0.990
6:13620468:T:C	F228S	0.990
6:13620284:T:C	F193L	0.989
6:13620286:C:A	F193L	0.989
6:13620286:C:G	F193L	0.989
6:13615564:T:G	F69C	0.988
6:13615772:G:C	K109N	0.988
6:13615772:G:T	K109N	0.988
6:13615747:G:C	R101P	0.987
6:13615759:T:C	F105S	0.985
6:13615769:G:C	Q108H	0.984
6:13615769:G:T	Q108H	0.984
6:13620275:G:C	A190P	0.983
6:13620436:G:C	K217N	0.983
6:13620436:G:T	K217N	0.983
6:13620459:C:A	A225D	0.983
6:13615738:G:C	R98T	0.982
6:13620228:C:A	A174D	0.982

dbSNP variants (sampled 300 via entrez): RS1000324763 (6:13623646 T>A,C), RS1000448896 (6:13629095 A>T), RS1000480050 (6:13629328 A>G), RS1000655567 (6:13623413 G>C), RS1000702650 (6:13617248 C>G,T), RS1000734236 (6:13622638 A>C,G), RS1000755137 (6:13616924 C>T), RS1000772987 (6:13618770 A>G), RS1000841450 (6:13628776 A>T), RS1001100847 (6:13628549 G>A), RS1001173596 (6:13629902 T>C), RS1001248128 (6:13616284 G>A,C), RS1001268248 (6:13629686 T>A), RS1001410405 (6:13628014 G>C), RS1001456845 (6:13621136 A>C,G)

Disease associations

OMIM: gene MIM:611533 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
bisphenol A	increases expression, affects expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
deoxynivalenol	increases expression	1
methylparaben	decreases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
Glyphosate	affects methylation	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Methyl Methanesulfonate	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
beta-Naphthoflavone	affects cotreatment, decreases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3CJ	Abcam HEK293T NOL7 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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