NOL12

Summary

NOL12 (nucleolar protein 12, HGNC:28585) is a protein-coding gene on chromosome 22q13.1, encoding Nucleolar protein 12 (Q9UGY1). Multifunctional RNA binding protein that plays a role in RNA metabolism and DNA maintenance. It is a selective cancer dependency (DepMap: 79.6% of cell lines).

Enables identical protein binding activity. Predicted to be located in cytoplasm and nucleus. Predicted to be active in nucleolus.

Source: NCBI Gene 79159 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 55 total
• Cancer dependency (DepMap): dependent in 79.6% of screened cell lines
• MANE Select transcript: NM_024313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28585
Approved symbol	NOL12
Name	nucleolar protein 12
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC3731, Nop25, RRP17
Ensembl gene	ENSG00000273899
Ensembl biotype	protein_coding
Entrez	79159

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000359114, ENST00000438329, ENST00000468597, ENST00000474032, ENST00000484650, ENST00000493862, ENST00000611699, ENST00000902787

RefSeq mRNA: 1 — MANE Select: NM_024313 NM_024313

CCDS: CCDS13955

Canonical transcript exons

ENST00000359114 — 6 exons

Exon	Start	End
ENSE00001410571	37691174	37693474
ENSE00003721469	37690697	37690794
ENSE00003731400	37688850	37688992
ENSE00003737060	37687910	37688015
ENSE00003752271	37688312	37688360
ENSE00003850306	37686343	37686475

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 92.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2167 / max 163.6229, expressed in 1810 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192183	16.9141	1810
192184	4.2661	1625
192182	0.0235	3
192180	0.0082	3
192181	0.0047	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.21	gold quality
right testis	UBERON:0004534	92.07	gold quality
left testis	UBERON:0004533	91.91	gold quality
monocyte	CL:0000576	91.79	gold quality
mononuclear cell	CL:0000842	91.41	gold quality
mucosa of transverse colon	UBERON:0004991	91.34	gold quality
leukocyte	CL:0000738	91.02	gold quality
lower esophagus mucosa	UBERON:0035834	90.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.62	gold quality
right adrenal gland	UBERON:0001233	89.56	gold quality
esophagus mucosa	UBERON:0002469	89.32	gold quality
granulocyte	CL:0000094	89.19	gold quality
cerebellar hemisphere	UBERON:0002245	89.18	gold quality
left adrenal gland cortex	UBERON:0035825	89.15	gold quality
left adrenal gland	UBERON:0001234	89.12	gold quality
right adrenal gland cortex	UBERON:0035827	89.09	gold quality
cerebellar cortex	UBERON:0002129	89.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.83	gold quality
right lobe of thyroid gland	UBERON:0001119	88.11	gold quality
transverse colon	UBERON:0001157	87.67	gold quality
testis	UBERON:0000473	87.43	gold quality
left lobe of thyroid gland	UBERON:0001120	87.39	gold quality
adrenal cortex	UBERON:0001235	87.05	gold quality
anterior cingulate cortex	UBERON:0009835	87.00	gold quality
cingulate cortex	UBERON:0003027	86.84	gold quality
right frontal lobe	UBERON:0002810	86.66	gold quality
cerebellum	UBERON:0002037	86.65	gold quality
ectocervix	UBERON:0012249	86.55	gold quality
skin of abdomen	UBERON:0001416	86.53	gold quality
minor salivary gland	UBERON:0001830	86.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting NOL12, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-342-5P	97.25	64.10	817

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 79.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Nol12 is an RNA binding protein required for both ribosome maturation and genome integrity (PMID:29069457)
• Results show that NOL12 is important for nucleolar homeostasis, regulating its structure and the nucleolar levels of the multifunctional fibrillarin and nucleolin proteins. Moreover, NOL12 depletion to induce strong p53 activation leading to cell senescence suggesting an important role for NOL12 in replicative and chronological aging and its potential as aging biomarker. (PMID:30988155)
• The human cellular protein NoL12 is a specific partner of the HIV-1 nucleocapsid protein NCp7. (PMID:37695057)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nol12	ENSDARG00000038027
mus_musculus	Nol12	ENSMUSG00000033099
rattus_norvegicus	Nol12	ENSRNOG00000010209

Protein

Protein identifiers

Nucleolar protein 12 — Q9UGY1 (reviewed: Q9UGY1)

All UniProt accessions (1): Q9UGY1

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional RNA binding protein that plays a role in RNA metabolism and DNA maintenance. Participates in the resolution of DNA stress and the maintenance of genome integrity by localizing to sites of DNA insults. Also plays a role in proper nucleolar organization by limiting nucleolar size and regulating nucleolar number. Mechanistically, regulates the nucleolar levels of fibrillarin and nucleolin, two key players in pre-rRNA processing and ribosome assembly.

Subunit / interactions. Interacts with KIAA1191.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Similarity. Belongs to the RRP17 family.

RefSeq proteins (1): NP_077289* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019186	Nucleolar_protein_12	Family

Pfam: PF09805

UniProt features (7 total): compositionally biased region 2, mutagenesis site 2, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGY1-F1	74.94	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
21	loss of dna damage response pathway activation.
23	loss of dna damage response pathway activation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 108 (showing top): SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, TATA_C, DOUGLAS_BMI1_TARGETS_UP, MODULE_397, GOMF_SINGLE_STRANDED_DNA_BINDING, REACTOME_METABOLISM_OF_RNA, chr22q13, GOCC_NUCLEOLUS, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, GEORGES_TARGETS_OF_MIR192_AND_MIR215, MANALO_HYPOXIA_DN, GOMF_RRNA_BINDING, AKT_UP_MTOR_DN.V1_UP, SRC_UP.V1_DN

GO Biological Process (0):

GO Molecular Function (5): single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), rRNA binding (GO:0019843), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): nucleolus (GO:0005730), cytoplasm (GO:0005737), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA binding	1
nucleic acid binding	1
RNA binding	1
protein binding	1
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOL12	BOP1	Q14137	615
NOL12	RRP1	P56182	531
NOL12	EBNA1BP2	Q99848	528
NOL12	RRP7A	Q9Y3A4	493
NOL12	RBM28	Q9NW13	478
NOL12	NOL6	Q9H6R4	474
NOL12	XRN2	Q9H0D6	473
NOL12	WDR12	Q9GZL7	460
NOL12	RBMX	P38159	433
NOL12	UTP18	Q9Y5J1	431
NOL12	A0A0A6YYI9	A0A0A6YYI9	425
NOL12	KIAA1191	Q96A73	422
NOL12	RPF2	Q9H7B2	421
NOL12	NOP56	O00567	411
NOL12	RBM14	Q96PK6	410

IntAct

126 interactions, top by confidence:

A	B	Type	Score
CEP70	NOL12	psi-mi:“MI:0915”(physical association)	0.670
NOL12	CEP70	psi-mi:“MI:0915”(physical association)	0.670
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
RPL7A	NOP56	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
KRTAP10-7	NOL12	psi-mi:“MI:0915”(physical association)	0.560
DVL3	NOL12	psi-mi:“MI:0915”(physical association)	0.560
SSX2IP	NOL12	psi-mi:“MI:0915”(physical association)	0.560
NOL12	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
NOL12	DVL3	psi-mi:“MI:0915”(physical association)	0.560
NOL12	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
CDCA7L	NOL12	psi-mi:“MI:0915”(physical association)	0.560
MCC	NOL12	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	NOL12	psi-mi:“MI:0915”(physical association)	0.560
TSPYL2	NOL12	psi-mi:“MI:0915”(physical association)	0.560
BEND7	NOL12	psi-mi:“MI:0915”(physical association)	0.560
SPANXN2	NOL12	psi-mi:“MI:0915”(physical association)	0.560
NOL12	NOL12	psi-mi:“MI:0915”(physical association)	0.560
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
ZCRB1	DKC1	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530

BioGRID (248): NOL12 (Two-hybrid), CEP70 (Two-hybrid), SSX2IP (Two-hybrid), KRTAP10-7 (Two-hybrid), NOL12 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), MRPS9 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), MRPS26 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), DDX50 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P2, A6QNR1, A8WY26, D3ZND0, O15213, O59678, P27672, P78316, Q0V8M0, Q15050, Q24K12, Q28IV8, Q2KIH4, Q2KII6, Q3T0Q8, Q3T0Z5, Q3UFY0, Q4KLC4, Q5M985, Q5RAS1, Q5RJT2, Q5TAP6, Q5TJE7, Q5ZKM1, Q640M1, Q6EJB6, Q6P0I6, Q6PFJ1, Q8BK35, Q8IY81, Q8N9T8, Q8NEJ9, Q8R3N1, Q8VDQ9, Q96BZ8, Q96EU6, Q9BRP8, Q9BRR8, Q9BVJ6, Q9C086

Diamond homologs: O14012, Q04031, Q0IH29, Q2KIV0, Q5D1Z3, Q5RD68, Q640V3, Q8BG17, Q9UGY1, Q7ZWE7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
Eukaryotic Translation Initiation	8	35.8×	7e-10
Cap-dependent Translation Initiation	8	35.8×	7e-10
SARS-CoV-1 modulates host translation machinery	8	35.8×	7e-10
Peptide chain elongation	19	34.9×	6e-23
Viral mRNA Translation	19	34.9×	6e-23
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	19	34.6×	6e-23
Selenocysteine synthesis	19	33.1×	9e-23
Eukaryotic Translation Termination	19	33.1×	9e-23

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	20	38.2×	4e-24
ribosomal large subunit biogenesis	7	32.0×	2e-07
ribosomal small subunit biogenesis	11	25.8×	5e-11
rRNA processing	14	20.4×	9e-13
translation	19	20.1×	2e-17
RNA processing	5	11.3×	3e-03
nucleosome assembly	7	10.1×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1174 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37686473:GCG:G	donor_gain	1.0000
22:37686474:CGGTG:C	donor_loss	1.0000
22:37686476:G:C	donor_loss	1.0000
22:37686476:G:GG	donor_gain	1.0000
22:37686476:GTGA:G	donor_loss	1.0000
22:37686477:T:A	donor_loss	1.0000
22:37686477:T:G	donor_loss	1.0000
22:37687893:C:A	acceptor_gain	1.0000
22:37687906:GTA:G	acceptor_loss	1.0000
22:37687907:TAGGG:T	acceptor_gain	1.0000
22:37687908:A:AC	acceptor_loss	1.0000
22:37687908:A:AT	acceptor_loss	1.0000
22:37687908:AG:A	acceptor_gain	1.0000
22:37687908:AGGGA:A	acceptor_gain	1.0000
22:37687909:G:GT	acceptor_gain	1.0000
22:37687909:G:T	acceptor_loss	1.0000
22:37687909:GG:G	acceptor_gain	1.0000
22:37687909:GGGA:G	acceptor_gain	1.0000
22:37687909:GGGAG:G	acceptor_gain	1.0000
22:37688000:G:GT	donor_gain	1.0000
22:37688012:GGAG:G	donor_gain	1.0000
22:37688013:G:GT	donor_gain	1.0000
22:37688013:GAG:G	donor_gain	1.0000
22:37688016:G:GA	donor_loss	1.0000
22:37688016:G:GG	donor_gain	1.0000
22:37688301:T:TA	acceptor_gain	1.0000
22:37688303:T:TA	acceptor_gain	1.0000
22:37688304:G:A	acceptor_gain	1.0000
22:37688308:TCAGC:T	acceptor_loss	1.0000
22:37688309:CAGC:C	acceptor_loss	1.0000

AlphaMissense

1365 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37687926:T:C	F34L	0.999
22:37687928:C:A	F34L	0.999
22:37687928:C:G	F34L	0.999
22:37688925:T:A	V105D	0.998
22:37686456:T:C	F22L	0.997
22:37686458:C:A	F22L	0.997
22:37686458:C:G	F22L	0.997
22:37687927:T:C	F34S	0.997
22:37687948:G:C	R41P	0.996
22:37687915:A:C	Y30S	0.995
22:37687929:C:G	H35D	0.994
22:37686473:G:C	R27S	0.993
22:37686473:G:T	R27S	0.993
22:37687914:T:G	Y30D	0.993
22:37687924:G:A	G33D	0.993
22:37687936:G:C	R37P	0.993
22:37688313:G:C	R64P	0.993
22:37686472:G:T	R27M	0.992
22:37687959:G:C	A45P	0.992
22:37686457:T:C	F22S	0.991
22:37687927:T:G	F34C	0.991
22:37688931:T:A	V107E	0.991
22:37687960:C:A	A45D	0.990
22:37686472:G:C	R27T	0.989
22:37687914:T:A	Y30N	0.989
22:37687923:G:C	G33R	0.989
22:37687952:G:C	K42N	0.989
22:37687952:G:T	K42N	0.989
22:37687914:T:C	Y30H	0.987
22:37687935:C:G	R37G	0.987

dbSNP variants (sampled 300 via entrez): RS1000819859 (22:37690157 G>A), RS1000875917 (22:37686765 C>G,T), RS1000890775 (22:37690451 T>C), RS1001241854 (22:37685460 A>C), RS1001640954 (22:37686268 G>A), RS1002007416 (22:37688250 C>A,G,T), RS1002205971 (22:37690892 C>A,G,T), RS1002627490 (22:37685852 T>C), RS1002674965 (22:37686215 G>C,T), RS1003570283 (22:37693020 G>A,C,T), RS1003629499 (22:37686997 G>A), RS1003682028 (22:37687161 G>A,T), RS1003701614 (22:37688146 G>A), RS1003925933 (22:37691758 C>T), RS1003980367 (22:37692500 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006629_43	Pulse pressure	5.000000e-11
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10
GCST90002379_171	Basophil count	6.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004346	neuroimaging measurement
EFO:0005090	basophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Copper	affects binding, decreases expression	1
Disulfiram	decreases expression, affects binding	1
Doxorubicin	increases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	decreases phosphorylation	1
Ribonucleotides	affects binding	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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