NOC4L

Summary

NOC4L (nucleolar complex associated 4 homolog, HGNC:28461) is a protein-coding gene on chromosome 12q24.33, encoding Nucleolar complex protein 4 homolog (Q9BVI4). It is a common-essential gene (DepMap: required in 97.8% of cancer cell lines).

Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in nucleolus and nucleoplasm.

Source: NCBI Gene 79050 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 176 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_024078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28461
Approved symbol	NOC4L
Name	nucleolar complex associated 4 homolog
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC3162, NET49, UTP19, Noc4
Ensembl gene	ENSG00000184967
Ensembl biotype	protein_coding
OMIM	612819
Entrez	79050

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000330579, ENST00000535343, ENST00000538784, ENST00000541954, ENST00000896508, ENST00000896509, ENST00000896510, ENST00000896511, ENST00000921233, ENST00000921234, ENST00000962464, ENST00000962465, ENST00000962466, ENST00000962467, ENST00000962468, ENST00000962469

RefSeq mRNA: 6 — MANE Select: NM_024078 NM_001414688, NM_001414689, NM_001414690, NM_001414691, NM_001414692, NM_024078

CCDS: CCDS9277

Canonical transcript exons

ENST00000330579 — 15 exons

Exon	Start	End
ENSE00001293047	132145559	132145665
ENSE00001294208	132147633	132147782
ENSE00001294266	132144457	132144605
ENSE00001294702	132150981	132151041
ENSE00001307221	132152282	132152468
ENSE00001309867	132144854	132144974
ENSE00001313868	132147281	132147388
ENSE00003468566	132148609	132148659
ENSE00003486153	132151258	132151368
ENSE00003497866	132147880	132147979
ENSE00003549873	132151484	132151644
ENSE00003609755	132148784	132148895
ENSE00003677851	132148072	132148106
ENSE00003718418	132152084	132152197
ENSE00003749177	132151738	132151820

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8528 / max 180.7340, expressed in 1798 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128784	17.8528	1798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	93.78	gold quality
left testis	UBERON:0004533	93.59	gold quality
testis	UBERON:0000473	92.50	gold quality
mucosa of transverse colon	UBERON:0004991	90.88	gold quality
gastrocnemius	UBERON:0001388	88.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.54	gold quality
right ovary	UBERON:0002118	87.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.58	gold quality
granulocyte	CL:0000094	87.57	gold quality
muscle of leg	UBERON:0001383	87.55	gold quality
left ovary	UBERON:0002119	87.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.36	gold quality
spleen	UBERON:0002106	87.22	gold quality
body of stomach	UBERON:0001161	87.15	gold quality
skin of leg	UBERON:0001511	87.14	gold quality
metanephros cortex	UBERON:0010533	87.04	gold quality
left uterine tube	UBERON:0001303	86.99	gold quality
pituitary gland	UBERON:0000007	86.81	gold quality
zone of skin	UBERON:0000014	86.76	gold quality
skin of abdomen	UBERON:0001416	86.74	gold quality
right lobe of liver	UBERON:0001114	86.41	gold quality
ovary	UBERON:0000992	86.40	gold quality
apex of heart	UBERON:0002098	86.26	gold quality
right lobe of thyroid gland	UBERON:0001119	86.24	gold quality
right frontal lobe	UBERON:0002810	86.22	gold quality
left lobe of thyroid gland	UBERON:0001120	86.08	gold quality
prostate gland	UBERON:0002367	86.07	gold quality
tibial nerve	UBERON:0001323	86.02	gold quality
body of uterus	UBERON:0009853	85.93	gold quality
cortex of kidney	UBERON:0001225	85.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.71
E-MTAB-6386	no	128.51

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• The results provide the first in vivo genetic evidence that Noc4l plays important roles in early embryogenesis in mice. (PMID:28012024)
• Oncogenic fusion transcript analysis identified ADAP1-NOC4L, potentially associated with metastatic colorectal cancer. (PMID:35702822)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	noc4l	ENSDARG00000045565
mus_musculus	Noc4l	ENSMUSG00000033294
rattus_norvegicus	Noc4l	ENSRNOG00000037478
drosophila_melanogaster	CG2875	FBGN0029672
caenorhabditis_elegans		WBGENE00020601

Protein

Protein identifiers

Nucleolar complex protein 4 homolog — Q9BVI4 (reviewed: Q9BVI4)

Alternative names: NOC4-like protein, Nucleolar complex-associated protein 4-like protein

All UniProt accessions (2): Q9BVI4, F5H303

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus membrane. Nucleus. Nucleolus.

Similarity. Belongs to the CBF/MAK21 family.

RefSeq proteins (6): NP_001401617, NP_001401618, NP_001401619, NP_001401620, NP_001401621, NP_076983* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005612	CCAAT-binding_factor	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027193	NOC4-like	Family

Pfam: PF03914

UniProt features (4 total): transmembrane region 3, chain 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-Q9BVI4-F1	89.48	0.64

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: 150 (showing top): GOBP_RIBOSOME_BIOGENESIS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, CREBP1_Q2, CREB_Q4, FOSTER_TOLERANT_MACROPHAGE_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, CREB_Q2_01, ATF4_Q2, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, CUI_TCF21_TARGETS_2_UP, CREBP1CJUN_01, REACTOME_METABOLISM_OF_RNA

GO Biological Process (2): rRNA processing (GO:0006364), ribosome biogenesis (GO:0042254)

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

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolus (GO:0005730), Noc4p-Nop14p complex (GO:0030692), nuclear membrane (GO:0031965), small-subunit processome (GO:0032040), nucleus (GO:0005634), membrane (GO:0016020)

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

Protein interactions and networks

STRING

2727 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOC4L	NOP14	P78316	821
NOC4L	UTP14A	Q9BVJ6	650
NOC4L	BYSL	Q13895	642
NOC4L	LTV1	Q96GA3	629
NOC4L	RRP12	Q5JTH9	625
NOC4L	RIOK2	Q9BVS4	573
NOC4L	EMG1	Q92979	572
NOC4L	TSR1	Q2NL82	560
NOC4L	UTP15	Q8TED0	557
NOC4L	DPY19L4	Q7Z388	531
NOC4L	SLX9	Q9NSI2	506
NOC4L	TMEM9B	Q9NQ34	500
NOC4L	CCNQ	Q8N1B3	493
NOC4L	VWA7	Q9Y334	483
NOC4L	PWP2	Q15269	480

IntAct

215 interactions, top by confidence:

A	B	Type	Score
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
SEC31A	SEC13	psi-mi:“MI:0914”(association)	0.730
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NOC4L	KRT15	psi-mi:“MI:0915”(physical association)	0.670
KRT15	NOC4L	psi-mi:“MI:0915”(physical association)	0.670
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
BYSL	PARN	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
RACK1	RIOK3	psi-mi:“MI:0914”(association)	0.640
BHLHE40	NOC4L	psi-mi:“MI:0915”(physical association)	0.560
NOC4L	IKZF1	psi-mi:“MI:0915”(physical association)	0.560
NOC4L	DNAJA3	psi-mi:“MI:0915”(physical association)	0.560
NOC4L	BHLHE40	psi-mi:“MI:0915”(physical association)	0.560
IKZF1	NOC4L	psi-mi:“MI:0915”(physical association)	0.560
DNAJA3	NOC4L	psi-mi:“MI:0915”(physical association)	0.560
NOC4L	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
NOC4L	LNPK	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (231): NOC4L (Two-hybrid), NOC4L (Two-hybrid), NOC4L (Two-hybrid), NOC4L (Two-hybrid), NOC4L (Affinity Capture-MS), NOC4L (Affinity Capture-MS), NOC4L (Affinity Capture-MS), NOC4L (Affinity Capture-MS), NOC4L (Affinity Capture-MS), NOC4L (Affinity Capture-MS), NOC4L (Affinity Capture-MS), NOC4L (Two-hybrid), NOC4L (Two-hybrid), NOC4L (Two-hybrid), NOC4L (Two-hybrid)

ESM2 similar proteins: A0A5F8AH41, A0AVI4, A0JMH2, A1Y9I9, A5WVX1, B0X4N1, B4P925, D3ZX08, O55171, O88512, O95050, O97972, P0DPD7, P0DPE0, P0DPE1, P10937, P10938, P11086, P40935, P40936, Q06AU9, Q08DK0, Q14CH7, Q32PE2, Q32Q92, Q3SZG9, Q3URQ7, Q568P9, Q5E9L5, Q5JTZ9, Q5RCH4, Q5RFR7, Q6NTR1, Q6NZB1, Q7QIL2, Q7TMC8, Q80YU0, Q8HY87, Q8K304, Q8NFF5

Diamond homologs: F4IMH3, O94372, P41843, Q06512, Q4VBT2, Q5I0I8, Q5ZJC7, Q6NRQ2, Q8BHY2, Q9BVI4, F4IDJ0, Q6NU91, P91136, Q5R952, Q5XGZ8, Q61LN7, Q6DRN3, Q8VI84, Q8WTT2, Q91Y26, Q9VI82

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 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	7	18.9×	1e-06
Cap-dependent Translation Initiation	7	18.9×	1e-06
SARS-CoV-1 modulates host translation machinery	7	18.9×	1e-06
Peptide chain elongation	16	17.8×	6e-14
Viral mRNA Translation	16	17.8×	6e-14
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	16	17.6×	6e-14
Eukaryotic Translation Elongation	7	17.1×	3e-06
Influenza Viral RNA Transcription and Replication	9	17.0×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	6	24.5×	2e-05
maturation of SSU-rRNA	5	23.2×	2e-04
cytoplasmic translation	19	21.3×	2e-17
ribosomal small subunit biogenesis	14	19.3×	6e-12
ribosomal large subunit biogenesis	7	18.8×	1e-05
rRNA processing	16	13.7×	1e-11
translation	17	10.6×	1e-10
RNA processing	6	8.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	136
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2265 predictions. Top by Δscore:

Variant	Effect	Δscore
12:132144687:G:GT	donor_gain	1.0000
12:132147277:CCAG:C	acceptor_loss	1.0000
12:132147278:CAG:C	acceptor_loss	1.0000
12:132147279:A:AG	acceptor_gain	1.0000
12:132147280:G:A	acceptor_loss	1.0000
12:132147280:G:GG	acceptor_gain	1.0000
12:132147280:GGA:G	acceptor_gain	1.0000
12:132147386:AAGG:A	donor_loss	1.0000
12:132147387:AGGT:A	donor_loss	1.0000
12:132147389:GTG:G	donor_loss	1.0000
12:132147390:T:A	donor_loss	1.0000
12:132147629:CTAGT:C	acceptor_loss	1.0000
12:132147631:A:AG	acceptor_gain	1.0000
12:132147631:A:T	acceptor_loss	1.0000
12:132147631:AGTT:A	acceptor_gain	1.0000
12:132147631:AGTTG:A	acceptor_gain	1.0000
12:132147632:G:GT	acceptor_gain	1.0000
12:132147632:GT:G	acceptor_gain	1.0000
12:132147632:GTT:G	acceptor_gain	1.0000
12:132147632:GTTG:G	acceptor_gain	1.0000
12:132147632:GTTGG:G	acceptor_gain	1.0000
12:132147634:T:A	acceptor_gain	1.0000
12:132147779:CGAGG:C	donor_loss	1.0000
12:132147781:AGGT:A	donor_loss	1.0000
12:132147975:GGCGG:G	donor_gain	1.0000
12:132147976:GCGGG:G	donor_gain	1.0000
12:132148071:GA:G	acceptor_gain	1.0000
12:132148071:GAGCT:G	acceptor_gain	1.0000
12:132148104:AAGG:A	donor_loss	1.0000
12:132148107:G:GA	donor_loss	1.0000

AlphaMissense

3329 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:132148636:T:A	W256R	0.990
12:132148636:T:C	W256R	0.990
12:132151520:G:C	K370N	0.990
12:132151520:G:T	K370N	0.990
12:132151800:A:C	S433R	0.989
12:132151802:C:A	S433R	0.989
12:132151802:C:G	S433R	0.989
12:132145606:T:G	Y96D	0.984
12:132151016:T:C	F313L	0.977
12:132151018:C:A	F313L	0.977
12:132151018:C:G	F313L	0.977
12:132144905:T:C	F57L	0.976
12:132144907:C:A	F57L	0.976
12:132144907:C:G	F57L	0.976
12:132151512:T:C	F368L	0.976
12:132151514:C:A	F368L	0.976
12:132151514:C:G	F368L	0.976
12:132145604:G:C	R95P	0.975
12:132151809:T:A	W436R	0.973
12:132151809:T:C	W436R	0.973
12:132151002:C:A	A308D	0.971
12:132151785:A:C	S428R	0.970
12:132151787:C:A	S428R	0.970
12:132151787:C:G	S428R	0.970
12:132145593:G:C	W91C	0.965
12:132145593:G:T	W91C	0.965
12:132151355:T:C	F354L	0.965
12:132151357:C:A	F354L	0.965
12:132151357:C:G	F354L	0.965
12:132151507:C:A	A366D	0.965

dbSNP variants (sampled 300 via entrez): RS1000269617 (12:132142812 G>A,C,T), RS1000492604 (12:132151290 G>A), RS1000521431 (12:132143414 C>G,T), RS1000819124 (12:132143415 G>A), RS1000977919 (12:132147451 C>G,T), RS1001086236 (12:132151727 C>T), RS1001199394 (12:132143663 C>A,G,T), RS1001292427 (12:132152426 T>C), RS1001441923 (12:132151892 G>A,T), RS1001533438 (12:132144202 C>A,T), RS1001675951 (12:132151147 T>C), RS1001689037 (12:132143688 G>A,T), RS1002039657 (12:132143241 A>G), RS1002099293 (12:132148512 G>A,C,T), RS1002126813 (12:132147046 G>A,T)

Disease associations

OMIM: gene MIM:612819 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005951_3	Body mass index	6.000000e-09
GCST007059_15	Response to antidepressants (symptom improvement)	5.000000e-06
GCST007060_6	Response to SSRI (symptom remission)	3.000000e-06
GCST008016_1	Hirschsprung disease	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005658	response to selective serotonin reuptake inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725186 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
MT19c compound	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1
tert-Butylhydroperoxide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697662	Binding	Inhibition of NOC4L (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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