NOL4L

Summary

NOL4L (nucleolar protein 4 like, HGNC:16106) is a protein-coding gene on chromosome 20q11.21, encoding Nucleolar protein 4-like (Q96MY1).

Located in cytosol and nucleoplasm.

Source: NCBI Gene 140688 — RefSeq curated summary.

At a glance

• GWAS associations: 44
• Clinical variants (ClinVar): 76 total — 1 pathogenic
• MANE Select transcript: NM_001256798

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16106
Approved symbol	NOL4L
Name	nucleolar protein 4 like
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ1184F4.2, DKFZP566G1424, dJ1184F4.4
Ensembl gene	ENSG00000197183
Ensembl biotype	protein_coding
OMIM	618893
Entrez	140688

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000201961, ENST00000326071, ENST00000359676, ENST00000375677, ENST00000375678, ENST00000419612, ENST00000470428, ENST00000475781, ENST00000485364, ENST00000621426

RefSeq mRNA: 3 — MANE Select: NM_001256798 NM_001256798, NM_001351680, NM_080616

CCDS: CCDS13202, CCDS74718

Canonical transcript exons

ENST00000621426 — 11 exons

Exon	Start	End
ENSE00001243514	32443059	32447816
ENSE00003733369	32584570	32585333
ENSE00003802350	32453576	32453761
ENSE00003802443	32520811	32520922
ENSE00003803968	32456118	32456395
ENSE00003805831	32452884	32453006
ENSE00003806042	32511347	32511456
ENSE00003806358	32527758	32527913
ENSE00003806652	32452236	32452437
ENSE00003808041	32453304	32453495
ENSE00003810753	32474601	32474742

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.4512 / max 3310.7233, expressed in 1794 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186910	13.8069	1616
186919	10.0307	1592
186936	2.3369	652
186935	1.2923	620
186921	0.4313	216
186912	0.2989	164
186933	0.2666	128
186920	0.2589	108
186934	0.2350	114
186917	0.2209	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.82	gold quality
cortical plate	UBERON:0005343	95.95	gold quality
left testis	UBERON:0004533	94.11	gold quality
right testis	UBERON:0004534	93.84	gold quality
thymus	UBERON:0002370	93.28	gold quality
testis	UBERON:0000473	92.42	gold quality
sperm	CL:0000019	92.22	gold quality
kidney epithelium	UBERON:0004819	92.06	gold quality
jejunal mucosa	UBERON:0000399	91.12	gold quality
secondary oocyte	CL:0000655	91.07	gold quality
ganglionic eminence	UBERON:0004023	90.65	gold quality
embryo	UBERON:0000922	90.64	gold quality
pigmented layer of retina	UBERON:0001782	89.73	gold quality
retina	UBERON:0000966	89.70	gold quality
mucosa of transverse colon	UBERON:0004991	89.44	gold quality
inferior vagus X ganglion	UBERON:0005363	89.33	gold quality
subthalamic nucleus	UBERON:0001906	88.73	gold quality
adenohypophysis	UBERON:0002196	88.62	gold quality
duodenum	UBERON:0002114	88.52	gold quality
parotid gland	UBERON:0001831	88.27	gold quality
pituitary gland	UBERON:0000007	88.10	gold quality
sural nerve	UBERON:0015488	88.04	gold quality
colonic mucosa	UBERON:0000317	87.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.79	gold quality
spinal cord	UBERON:0002240	87.75	gold quality
blood	UBERON:0000178	87.66	gold quality
granulocyte	CL:0000094	87.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.43	gold quality
cerebellar vermis	UBERON:0004720	87.40	gold quality
oocyte	CL:0000023	87.28	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	12.12
E-MTAB-6678	yes	9.39
E-ANND-3	yes	8.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

169 targeting NOL4L, 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-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-23B-5P	99.98	66.07	587
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960

Literature-anchored findings (GeneRIF, showing 4)

• report characterization of two chimeric transcripts identified in AML translocation cases involving CBFA2T2 and C20orf112 (PMID:20520637)
• the leukemogenic PAX5-C20S fusion protein is a tetramer, which interacts extraordinarily stably with chromatin as determined by Fluorescence Recovery After Photobleaching in living cells (PMID:21765475)
• LncRNA double homeobox A pseudogene 8 (DUXAP8) facilitates the progression of neuroblastoma and activates Wnt/beta-catenin pathway via microRNA-29/nucleolar protein 4 like (NOL4L) axis. (PMID:32522628)
• NOL4L, a novel nuclear protein, promotes cell proliferation and metastasis by enhancing the PI3K/AKT pathway in ovarian cancer. (PMID:33940382)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nol4lb	ENSDARG00000037607
mus_musculus	Nol4l	ENSMUSG00000061411
rattus_norvegicus	Nol4l	ENSRNOG00000010417

Paralogs (1): NOL4 (ENSG00000101746)

Protein

Protein identifiers

Nucleolar protein 4-like — Q96MY1 (reviewed: Q96MY1)

All UniProt accessions (8): A0A087X0N3, A0A1W2PQU1, Q96MY1, H0Y778, Q5JYB6, Q5JYC0, Q5JYC2, Q5W149

Isoforms (2)

UniProt ID	Names	Canonical?
Q96MY1-1	1	yes
Q96MY1-2	2

RefSeq proteins (3): NP_001243727, NP_001338609, NP_542183 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039788	NOL4/NOL4L	Family
IPR056549	HTH_NOL4	Domain

Pfam: PF23079

UniProt features (13 total): compositionally biased region 5, region of interest 2, splice variant 2, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MY1-F1	62.35	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 (2): 130, 295

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): RNGTGGGC_UNKNOWN, FXR_IR1_Q6, YAATNRNNNYNATT_UNKNOWN, CMYB_01, CHX10_01, USF_C, CAGCTG_AP4_Q5, NFKB_Q6, NKX61_01, AGTCTTA_MIR499, SOX9_B1, AML_Q6, MYCMAX_01, BILD_E2F3_ONCOGENIC_SIGNATURE, ACATTCC_MIR1_MIR206

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOL4L	PAX5	Q02548	577
NOL4L	FAM227B	Q96M60	499
NOL4L	KIF3B	O15066	475
NOL4L	RUNX1	Q01196	461
NOL4L	ETV6	P41212	433
NOL4L	TM9SF4	Q92544	430
NOL4L	A0A2R8Y455	A0A2R8Y455	408
NOL4L	COMMD7	Q86VX2	406
NOL4L	LYG1	Q8N1E2	398
NOL4L	ZNF384	Q8TF68	376
NOL4L	ZSWIM3	Q96MP5	372
NOL4L	AUTS2	Q8WXX7	370
NOL4L	OR4L1	Q8NH43	369
NOL4L	IFT70A	Q86WT1	365
NOL4L	ASXL1	Q8IXJ9	360

IntAct

26 interactions, top by confidence:

A	B	Type	Score
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
NOL4L	CTBP2	psi-mi:“MI:0915”(physical association)	0.670
CTBP2	NOL4L	psi-mi:“MI:0915”(physical association)	0.670
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
SKA3	NOL4	psi-mi:“MI:0914”(association)	0.640
NOL4L	CTBP1	psi-mi:“MI:0915”(physical association)	0.560
NOL4L	CTBP2	psi-mi:“MI:0915”(physical association)	0.560
CTBP2	NOL4L	psi-mi:“MI:0915”(physical association)	0.560
SKA3	CCDC85C	psi-mi:“MI:0914”(association)	0.530
TEX9	NOL4	psi-mi:“MI:0914”(association)	0.530
SRPK1	NOL4L	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
CTBP2	ZEB2	psi-mi:“MI:0914”(association)	0.350
NOL4	ZNF195	psi-mi:“MI:0914”(association)	0.350
KLF15	TAF4	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (28): NOL4L (Two-hybrid), NOL4L (Two-hybrid), NOL4L (Affinity Capture-MS), NOL4L (Affinity Capture-MS), CTBP1 (Two-hybrid), NOL4L (Affinity Capture-MS), NOL4L (Affinity Capture-MS), NOL4L (Affinity Capture-MS), NOL4L (Affinity Capture-RNA), NOL4L (Protein-RNA), NOL4L (Negative Genetic), NOL4L (Affinity Capture-RNA), NOL4L (Affinity Capture-MS), NOL4L (Affinity Capture-MS), NOL4L (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1DMJ6, A0A0F0I5G4, A0A0S6XAX9, A0A0U2WFX7, A0A162LR42, A0A2U8U2L8, A0A5B9G902, A2QA83, B0Y9W4, B6GVZ2, B7WN96, E9F0C5, G4NBR8, J4UVD7, K9GKQ6, O13412, O13415, O13508, P09089, P10069, P10071, P17429, P19212, P22022, P22814, P37935, P40656, P45815, P53719, P78688, P80073, Q01168, Q01582, Q10136, Q24106, Q27403, Q2UQZ5, Q4WPF5, Q4WV91, Q58L83

Diamond homologs: O94818, P60954, Q5RFT9, Q6DIB4, Q96MY1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	60
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1526690	GRCh37/hg19 20p11.21-q11.22(chr20:25442597-33761550)	Pathogenic

SpliceAI

1915 predictions. Top by Δscore:

Variant	Effect	Δscore
20:32447563:C:A	donor_gain	1.0000
20:32452434:CATC:C	acceptor_gain	1.0000
20:32452436:TC:T	acceptor_gain	1.0000
20:32452436:TCCT:T	acceptor_loss	1.0000
20:32452437:CC:C	acceptor_gain	1.0000
20:32452879:GGTAC:G	donor_loss	1.0000
20:32452880:GTAC:G	donor_loss	1.0000
20:32452881:TA:T	donor_loss	1.0000
20:32452882:A:T	donor_loss	1.0000
20:32453002:CTGGT:C	acceptor_gain	1.0000
20:32453003:TGGT:T	acceptor_gain	1.0000
20:32453004:GGTCT:G	acceptor_loss	1.0000
20:32453005:GT:G	acceptor_gain	1.0000
20:32453007:C:CC	acceptor_gain	1.0000
20:32453007:CTGCA:C	acceptor_loss	1.0000
20:32453299:CTCA:C	donor_loss	1.0000
20:32453300:TCAC:T	donor_loss	1.0000
20:32453301:CACC:C	donor_loss	1.0000
20:32453302:A:AC	donor_gain	1.0000
20:32453302:AC:A	donor_gain	1.0000
20:32453302:ACCA:A	donor_loss	1.0000
20:32453302:ACCAT:A	donor_gain	1.0000
20:32453303:C:CA	donor_gain	1.0000
20:32453303:C:G	donor_loss	1.0000
20:32453303:CC:C	donor_gain	1.0000
20:32453303:CCA:C	donor_gain	1.0000
20:32453303:CCAT:C	donor_gain	1.0000
20:32453303:CCATC:C	donor_gain	1.0000
20:32453475:C:CT	acceptor_gain	1.0000
20:32453475:C:T	acceptor_gain	1.0000

AlphaMissense

4484 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:32447615:A:G	L431P	1.000
20:32447624:A:C	L428R	1.000
20:32447624:A:G	L428P	1.000
20:32447624:A:T	L428Q	1.000
20:32447633:G:T	A425E	1.000
20:32447634:C:G	A425P	1.000
20:32447636:G:A	S424F	1.000
20:32447636:G:T	S424Y	1.000
20:32447637:A:G	S424P	1.000
20:32447639:C:G	R423P	1.000
20:32447642:A:G	L422P	1.000
20:32447645:A:C	L421R	1.000
20:32447645:A:G	L421P	1.000
20:32447645:A:T	L421Q	1.000
20:32447647:G:C	F420L	1.000
20:32447647:G:T	F420L	1.000
20:32447648:A:C	F420C	1.000
20:32447648:A:G	F420S	1.000
20:32447649:A:C	F420V	1.000
20:32447649:A:G	F420L	1.000
20:32447649:A:T	F420I	1.000
20:32447652:C:G	A419P	1.000
20:32447654:G:T	A418D	1.000
20:32447655:C:G	A418P	1.000
20:32447657:G:A	S417F	1.000
20:32447658:A:G	S417P	1.000
20:32447660:T:A	E416V	1.000
20:32447661:C:T	E416K	1.000
20:32447663:C:G	R415P	1.000
20:32447666:T:C	Y414C	1.000

dbSNP variants (sampled 300 via entrez): RS1000049556 (20:32446694 G>A), RS1000056030 (20:32490268 T>C), RS1000061828 (20:32584095 T>A,C,G), RS1000072307 (20:32530497 C>G,T), RS1000078981 (20:32500292 C>T), RS1000101285 (20:32547906 C>G), RS1000117786 (20:32582875 G>C), RS1000148585 (20:32499730 C>A,G,T), RS1000158054 (20:32460664 A>G), RS1000167617 (20:32457177 G>A,T), RS1000231804 (20:32496464 T>C), RS1000237897 (20:32535266 T>C), RS1000263422 (20:32455170 G>A), RS1000264780 (20:32471790 A>G), RS1000267532 (20:32576882 C>T)

Disease associations

OMIM: gene MIM:618893 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST003795_9	Age at first birth	1.000000e-08
GCST004131_132	Inflammatory bowel disease	6.000000e-06
GCST004147_16	Chronic obstructive pulmonary disease	9.000000e-08
GCST004601_196	Red blood cell count	1.000000e-10
GCST004602_230	Mean corpuscular volume	3.000000e-23
GCST004611_161	High light scatter reticulocyte count	8.000000e-09
GCST004612_181	High light scatter reticulocyte percentage of red cells	3.000000e-11
GCST004621_171	Red cell distribution width	4.000000e-30
GCST004625_222	Monocyte count	5.000000e-17
GCST004628_121	Immature fraction of reticulocytes	3.000000e-13
GCST004630_72	Mean corpuscular hemoglobin	9.000000e-22
GCST005337_23	Headache	1.000000e-08
GCST006045_1	Age at first birth	1.000000e-06
GCST006481_38	Lung function (FEV1)	6.000000e-07
GCST006481_7	Lung function (FEV1)	4.000000e-08
GCST006804_100	Red cell distribution width	1.000000e-21
GCST007431_137	Lung function (FEV1/FVC)	1.000000e-13
GCST007432_200	FEV1	1.000000e-08
GCST007576_98	Chronotype	9.000000e-11
GCST007603_14	Smoking initiation	3.000000e-10
GCST007611_4	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	4.000000e-08
GCST008667_6	Smoking status (heavy vs never)	5.000000e-09
GCST009391_1666	Metabolite levels	2.000000e-06
GCST009411_7	Optic disc area	1.000000e-08
GCST010244_181	Triglyceride levels	2.000000e-08
GCST010344_3	TPE interval (recovery after exercise)	1.000000e-08
GCST011703_95	Smoking initiation	1.000000e-10
GCST90000050_82	Age at first birth	2.000000e-12
GCST90002379_159	Basophil count	4.000000e-15
GCST90002381_360	Eosinophil count	2.000000e-11

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0009101	age at first birth measurement
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0005091	monocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0008328	chronotype measurement
EFO:0005670	smoking initiation
EFO:0006527	smoking status measurement
EFO:0010470	carnosine measurement
EFO:0004530	triglyceride measurement
EFO:0004644	TPE interval measurement
EFO:0007768	response to exercise
EFO:0005090	basophil count
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	4
Aflatoxin B1	affects methylation, decreases methylation, increases expression	3
(+)-JQ1 compound	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Arsenic	increases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1

Clinical trials (associated diseases)

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