RPL3

Summary

RPL3 (ribosomal protein L3, HGNC:10332) is a protein-coding gene on chromosome 22q13.1, encoding Large ribosomal subunit protein uL3 (P39023). Component of the large ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Ribosomes, the complexes that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene’s introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6122 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 75 total
• Regional missense constraint (gnomAD): 2 of 5 regions constrained (≈9% of expected missense variation)
• GTEx eGene: eQTL in 28 tissues, sQTL in 12 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.17 (highly constrained)
• MANE Select transcript: NM_000967
• Interaction hub: 4,312 STRING partners (top 1% of genes corpus-wide)
• Notable: 75 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10332
Approved symbol	RPL3
Name	ribosomal protein L3
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	L3, uL3
Ensembl gene	ENSG00000100316
Ensembl biotype	protein_coding
OMIM	604163
Entrez	6122

Gene structure

Transcript identifiers

Ensembl transcripts: 76 — 37 protein_coding, 27 nonsense_mediated_decay, 9 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000216146

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 8, TSL 3: 2, TSL 5: 4

ENST00000216146, ENST00000401609, ENST00000402527, ENST00000420536, ENST00000427905, ENST00000453303, ENST00000459859, ENST00000460589, ENST00000461967, ENST00000464182, ENST00000465618, ENST00000467105, ENST00000471290, ENST00000473638, ENST00000481985, ENST00000484358, ENST00000484615, ENST00000498462, ENST00000871468, ENST00000871469, ENST00000871470, ENST00000871471, ENST00000871472, ENST00000871473, ENST00000871474, ENST00000871475, ENST00000871476, ENST00000871477, ENST00000926227, ENST00000926228, ENST00000926229, ENST00000926230, ENST00000926231, ENST00000926232, ENST00000926233, ENST00000926234, ENST00000926235, ENST00000926236, ENST00000971220, ENST00000986715, ENST00000986716, ENST00000986722, ENST00000986724, ENST00001035153, ENST00001035155, ENST00001035158, ENST00001035159, ENST00001035169, ENST00001035170, ENST00001035172, ENST00001035174, ENST00001063542, ENST00001063550, ENST00001063553, ENST00001063574, ENST00001063579, ENST00001063582, ENST00001063587, ENST00001063588, ENST00001063594, ENST00001063597, ENST00001104621, ENST00001104622, ENST00001104623, ENST00001104624, ENST00001104625, ENST00001104626, ENST00001104627, ENST00001104628, ENST00001104629, ENST00001104630, ENST00001104631, ENST00001124466, ENST00001124467, ENST00001124468, ENST00001132524

RefSeq mRNA: 2 — MANE Select: NM_000967 NM_000967, NM_001033853

CCDS: CCDS13988

Canonical transcript exons

ENST00000216146 — 10 exons

Exon	Start	End
ENSE00000654709	39316706	39316841
ENSE00001555640	39312882	39312984
ENSE00003465930	39317461	39317629
ENSE00003521491	39313191	39313310
ENSE00003551427	39313634	39313729
ENSE00003597413	39314107	39314208
ENSE00003612364	39318400	39318592
ENSE00003639458	39314686	39314846
ENSE00003656428	39319595	39319623
ENSE00003788412	39315369	39315555

Expression profiles

Bgee: expression breadth ubiquitous, 307 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 284.0083 / max 2417.5874, expressed in 1826 samples.

Highest expression (Bgee): ovary, type B pancreatic cell, adenohypophysis, ventricular zone, upper arm skin.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RPL3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 12 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 40 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Visceral Omentum	eqtl	3.8e-08	+0.16	22:39296304:G:A
Heart Atrial Appendage	sqtl	5.9e-07	+2.31	22:39323800:G:A
Nerve Tibial	eqtl	8.5e-07	+0.15	22:39295444:A:T
Esophagus Muscularis	eqtl	4.2e-06	+0.17	22:39295444:A:T
Brain Nucleus accumbens basal ganglia	eqtl	9.4e-06	+0.23	22:39327330:T:C
Skin Sun Exposed Lower leg	eqtl	1.5e-05	-0.09	22:39282307:A:G
Testis	eqtl	1.5e-05	+0.18	22:39344073:G:A
Muscle Skeletal	sqtl	3.3e-05	+0.21	22:39346401:C:T
Adipose Subcutaneous	eqtl	6.0e-05	+0.09	22:39295216:G:A
Lung	eqtl	6.5e-05	+0.15	22:39362504:A:G
Esophagus Mucosa	eqtl	1.6e-04	+0.12	22:39322115:G:T
Ovary	sqtl	1.7e-04	-2.52	22:39310593:AAGAC:A
Stomach	eqtl	2.8e-04	-0.46	22:39337897:A:G
Artery Aorta	sqtl	3.3e-04	+2.33	22:39323800:G:A
Thyroid	eqtl	3.6e-04	+0.11	22:39295444:A:T
Brain Cerebellum	eqtl	7.4e-04	+0.19	22:39439582:A:G
Esophagus Gastroesophageal Junction	eqtl	8.9e-04	+0.14	22:39295216:G:A
Skin Not Sun Exposed Suprapubic	sqtl	9.4e-04	-1.92	22:39999443:C:T
Colon Sigmoid	eqtl	1.0e-03	+0.21	22:39316976:A:G
Breast Mammary Tissue	sqtl	1.4e-03	-1.16	22:38992983:G:A

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
194284	278.6855	1826
194279	1.9254	1026
194282	1.9124	1100
194281	1.3769	837
194283	0.0749	25
209481	0.0333	7

Top tissues by expression

showing 100 of 307 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.94	gold quality
right ovary	UBERON:0002118	99.93	gold quality
type B pancreatic cell	CL:0000169	99.92	gold quality
adenohypophysis	UBERON:0002196	99.92	gold quality
ventricular zone	UBERON:0003053	99.92	gold quality
upper arm skin	UBERON:0004263	99.92	gold quality
stromal cell of endometrium	CL:0002255	99.91	gold quality
pituitary gland	UBERON:0000007	99.91	gold quality
endocervix	UBERON:0000458	99.91	gold quality
ganglionic eminence	UBERON:0004023	99.91	gold quality
body of uterus	UBERON:0009853	99.91	gold quality
embryo	UBERON:0000922	99.90	gold quality
ovary	UBERON:0000992	99.90	gold quality
right uterine tube	UBERON:0001302	99.90	gold quality
skin of abdomen	UBERON:0001416	99.90	gold quality
skin of leg	UBERON:0001511	99.90	gold quality
right lobe of thyroid gland	UBERON:0001119	99.89	gold quality
left lobe of thyroid gland	UBERON:0001120	99.89	gold quality
mucosa of stomach	UBERON:0001199	99.89	gold quality
left uterine tube	UBERON:0001303	99.89	gold quality
cerebellar cortex	UBERON:0002129	99.89	gold quality
cerebellar hemisphere	UBERON:0002245	99.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.89	gold quality
ectocervix	UBERON:0012249	99.89	gold quality
zone of skin	UBERON:0000014	99.88	gold quality
left adrenal gland	UBERON:0001234	99.88	gold quality
left testis	UBERON:0004533	99.88	gold quality
cortical plate	UBERON:0005343	99.88	gold quality
metanephros cortex	UBERON:0010533	99.88	gold quality
lower esophagus	UBERON:0013473	99.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.88	gold quality
left adrenal gland cortex	UBERON:0035825	99.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.88	gold quality
body of pancreas	UBERON:0001150	99.87	gold quality
right adrenal gland	UBERON:0001233	99.87	gold quality
gall bladder	UBERON:0002110	99.87	gold quality
right testis	UBERON:0004534	99.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.87	gold quality
granulocyte	CL:0000094	99.86	gold quality
islet of Langerhans	UBERON:0000006	99.86	gold quality
lymph node	UBERON:0000029	99.86	gold quality
smooth muscle tissue	UBERON:0001135	99.86	gold quality
body of stomach	UBERON:0001161	99.86	gold quality
adrenal cortex	UBERON:0001235	99.86	gold quality
cerebellum	UBERON:0002037	99.86	gold quality
right adrenal gland cortex	UBERON:0035827	99.86	gold quality
lower esophagus mucosa	UBERON:0035834	99.86	gold quality
esophagus	UBERON:0001043	99.85	gold quality
caecum	UBERON:0001153	99.85	gold quality
vermiform appendix	UBERON:0001154	99.85	gold quality
minor salivary gland	UBERON:0001830	99.85	gold quality
peritoneum	UBERON:0002358	99.85	gold quality
adrenal gland	UBERON:0002369	99.85	gold quality
caput epididymis	UBERON:0004358	99.85	gold quality
upper lobe of lung	UBERON:0008948	99.85	gold quality
upper lobe of left lung	UBERON:0008952	99.85	gold quality
omental fat pad	UBERON:0010414	99.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.84	gold quality
peripheral nervous system	UBERON:0000010	99.84	gold quality
stomach	UBERON:0000945	99.84	gold quality
penis	UBERON:0000989	99.84	gold quality
nerve	UBERON:0001021	99.84	gold quality
transverse colon	UBERON:0001157	99.84	gold quality
fundus of stomach	UBERON:0001160	99.84	gold quality
urinary bladder	UBERON:0001255	99.84	gold quality
tibial nerve	UBERON:0001323	99.84	gold quality
skin of hip	UBERON:0001554	99.84	gold quality
right coronary artery	UBERON:0001625	99.84	gold quality
right lung	UBERON:0002167	99.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.84	gold quality
urethra	UBERON:0000057	99.83	gold quality
large intestine	UBERON:0000059	99.83	gold quality
mammalian vulva	UBERON:0000997	99.83	gold quality
colon	UBERON:0001155	99.83	gold quality
ascending aorta	UBERON:0001496	99.83	gold quality
thoracic aorta	UBERON:0001515	99.83	gold quality
spleen	UBERON:0002106	99.83	gold quality
thymus	UBERON:0002370	99.83	gold quality
esophagus mucosa	UBERON:0002469	99.83	gold quality
corpus epididymis	UBERON:0004359	99.83	gold quality
intestine	UBERON:0000160	99.82	gold quality
aorta	UBERON:0000947	99.82	gold quality
rectum	UBERON:0001052	99.82	gold quality
myometrium	UBERON:0001296	99.82	gold quality
artery	UBERON:0001637	99.82	gold quality
nipple	UBERON:0002030	99.82	gold quality
popliteal artery	UBERON:0002250	99.82	gold quality
descending thoracic aorta	UBERON:0002345	99.82	gold quality
upper leg skin	UBERON:0004262	99.82	gold quality
tibial artery	UBERON:0007610	99.82	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.82	gold quality
left coronary artery	UBERON:0001626	99.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.81	gold quality
right frontal lobe	UBERON:0002810	99.81	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.81	gold quality
adult organism	UBERON:0007023	99.81	gold quality
small intestine	UBERON:0002108	99.80	gold quality
cartilage tissue	UBERON:0002418	99.80	gold quality
seminal vesicle	UBERON:0000998	99.79	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	7901.80
E-HCAD-9	yes	5203.70
E-CURD-112	yes	5117.58
E-MTAB-9221	yes	4097.41
E-HCAD-35	yes	1725.56
E-CURD-122	yes	101.02
E-CURD-88	yes	60.28
E-MTAB-9067	yes	32.41
E-MTAB-9543	yes	23.57
E-MTAB-10042	yes	15.62
E-MTAB-9801	yes	6.84
E-MTAB-7249	no	37468.38
E-HCAD-4	no	13757.71
E-MTAB-10885	no	11928.16
E-MTAB-7606	no	11361.45

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	4364.6	low
Pancreas	tissue	4096.7	medium
Bone marrow	tissue	2796.4	medium
Skin 1	tissue	2664.9	high
Breast	tissue	2530.6	medium
Vagina	tissue	2384.9	medium
Lymph node	tissue	2303.1	medium
Fallopian tube	tissue	2281.0	medium
Tonsil	tissue	2175.1	medium
Salivary gland	tissue	2082.5	medium
Cervix	tissue	2027.4	medium
Pituitary gland	tissue	1890.0
Thymus	tissue	1870.2
Esophagus	tissue	1840.0	medium
Thyroid gland	tissue	1598.7	medium
Epididymis	tissue	1561.6	medium
Liver	tissue	1519.6	low
Urinary bladder	tissue	1516.6	medium
Stomach 1	tissue	1483.1	medium
Adrenal gland	tissue	1472.2	medium
Seminal vesicle	tissue	1461.8
Colon	tissue	1451.2	medium
Prostate	tissue	1425.8	low
Duodenum	tissue	1424.8	medium
Endometrium 1	tissue	1419.1	medium
Appendix	tissue	1400.3	medium
Parathyroid gland	tissue	1374.4	medium
Small intestine	tissue	1356.6	medium
Spleen	tissue	1314.1	low
Smooth muscle	tissue	1296.3	low
Rectum	tissue	1279.1	medium
Caudate putamen	tissue	1138.5
Gallbladder	tissue	1057.9	medium
Placenta	tissue	1033.6	medium
Adipose tissue	tissue	1021.5	low
Lung	tissue	915.8	medium
Kidney	tissue	913.4	low
Frontal cortex	tissue	857.6
Retina	tissue	750.8
Choroid plexus	tissue	736.4
Heart muscle	tissue	711.7	not detected
Testis	tissue	548.9	medium
Nucleus accumbens	tissue	548.6
Locus coeruleus	tissue	475.5
Hippocampus	tissue	446.8	medium
Tongue	tissue	389.4
Spinal cord	tissue	371.5
Postcentral gyrus	tissue	331.7
Superior colliculi	tissue	315.2
Pons	tissue	296.9
Thalamus	tissue	290.3
Midbrain	tissue	289.1
Medulla oblongata	tissue	284.4
Substantia nigra	tissue	279.0
Skeletal muscle	tissue	273.7	not detected
Corpus callosum	tissue	265.0
Hippocampal formation	tissue	256.1
Hypothalamus	tissue	252.5
Cerebral cortex	tissue	242.1	medium
Motor cortex	tissue	242.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (1815.9), Cervical spinal cord, ventral horn (806.8), Posterior thalamic nucleus (709.9), Lateral funiculus (white matter) (679.7), Nucleus ambiguus (656.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, KHSRP, MYC, NPM1

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.165, missense Z 2.45 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000216146 splits into 5 regions with different missense tolerance; 2 are missense-constrained (≈9% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
22:39,312,943–39,314,755	131 / 185.1	0.71	no
22:39,314,756–39,314,808	4 / 25.6	0.16	yes (p 2.0e-05)
22:39,314,809–39,315,504	48 / 80.7	0.60	no
22:39,315,505–39,318,538	196 / 217.5	0.90	no
22:39,318,539–39,319,597	8 / 23.8	0.34	yes (p 1.2e-03)
DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SNU-840 (-3.872), BT-12 (-3.784), OCI-LY-19 (-3.591), BHT-101 (-3.572), HT-1080 (-3.551), MOLM-13 (-3.516), NCI-H2122 (-3.433), SU-DHL-10 (-3.388), KMS-20 (-3.374), SNU-869 (-3.336), KMRC-20 (-3.311), JHOS-2 (-3.308), SNU-213 (-3.294), LS513 (-3.289), NCI-H2052 (-3.257).

Literature-anchored findings (GeneRIF, showing 16)

• Involved in progression and regulation of telomerase (PMID:16364039)
• working model in which rpL3 recruits hnRNP H1 and, through cooperation with other splicing factors, promotes selection of the alternative splice site (PMID:20100605)
• NPM and KHSRP are two newly identified proteins involved in the regulation of rpL3 gene expression via alternative pre-mRNA splicing. (PMID:21705779)
• The rpL3 is able to modulate the protein amounts of p21 through a novel pathway independent from p53 involving Sp1 and NPM. (PMID:23255119)
• rpL3 participates in the cell response to chemotherapy acting as a critical regulator of cell cycle, apoptosis and DNA repair, by modulating p21 expression (PMID:25473889)
• nucleolar stress induced by 5-fluorouracil in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 as proapoptotic factor (PMID:27385096)
• The sensitivity of p53 null colon cancer cells to 5-FU can be enhanced using proapoptotic rpL3 gene. (PMID:27835895)
• We found that uL3 down-regulation correlates positively with multidrug resistance. Restoration of the uL3 protein level re-sensitized the resistant cells to the drug by regulating the reactive oxygen species (ROS) levels, glutathione content, glutamate release, and cystine uptake. (PMID:28273808)
• Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress. (PMID:31659203)
• uL3 Mediated Nucleolar Stress Pathway as a New Mechanism of Action of Antiproliferative G-quadruplex TBA Derivatives in Colon Cancer Cells. (PMID:32290083)
• DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3. (PMID:32531052)
• S-Adenosyl-l-Methionine Overcomes uL3-Mediated Drug Resistance in p53 Deleted Colon Cancer Cells. (PMID:33374288)
• Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function. (PMID:33693809)
• Suppression of RPL34 Inhibits Tumor Cell Proliferation and Promotes Apoptosis in Glioblastoma. (PMID:35377127)
• METTL18-mediated histidine methylation of RPL3 modulates translation elongation for proteostasis maintenance. (PMID:35674491)
• BAIAP2L1 accelerates breast cancer progression and chemoresistance by activating AKT signaling through binding with ribosomal protein L3. (PMID:36308067)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl3	ENSDARG00000003599
mus_musculus	Rpl3	ENSMUSG00000060036
rattus_norvegicus	Rpl3	ENSRNOG00000016896
drosophila_melanogaster	RpL3	FBGN0020910
caenorhabditis_elegans		WBGENE00004414

Paralogs (1): RPL3L (ENSG00000140986)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1351605) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
prenatal lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Methanococcus vannielii SB	A6UQJ0	100.0%	Diamond
Halobacterium salinarum R1	B0R656	100.0%	Diamond
Saccharolobus islandicus L.S.2.15	C3MQ59	100.0%	Diamond
Saccharolobus islandicus M.14.25	C3MVH8	100.0%	Diamond
Saccharolobus islandicus Y.G.57.14	C3NEE3	100.0%	Diamond
Saccharolobus islandicus Y.N.15.51	C3NHA9	100.0%	Diamond
Saccharolobus islandicus M.16.4	C4KHF6	100.0%	Diamond
Halobacterium salinarum NRC-1	Q9HPD4	100.0%	Diamond
Methanococcus vannielii	Q9UWG2	100.0%	Diamond
Saccharolobus islandicus M.16.27	C3N5S7	99.7%	Diamond
Schizosaccharomyces pombe 972h-	P36584	99.7%	Diamond
Macaca fascicularis	Q4R5Q0	99.5%	Diamond
Bos taurus	P39872	99.3%	Diamond
Sus scrofa	Q29293	99.3%	Diamond
Methanococcus maripaludis C7	A6VHD2	99.1%	Diamond
Methanococcus maripaludis C6	A9A9B8	99.1%	Diamond
Methanococcus maripaludis C5	A4FVY2	98.5%	Diamond
Oryctolagus cuniculus	G1TL06	98.3%	Diamond
Methanococcus maripaludis S2	Q6LX10	97.9%	Diamond
Caenorhabditis briggsae	Q9NBK4	96.8%	Diamond
Pyrobaculum islandicum DSM 4184	A1RVG3	95.6%	Diamond
Pyrobaculum neutrophilum V24Sta	B1YD88	95.6%	Diamond
Pyrococcus horikoshii OT3	O59418	95.6%	Diamond
Pyrococcus abyssi GE5	Q9V1T5	95.6%	Diamond
Methanosarcina mazei Go1	Q8PV50	94.4%	Diamond
Methanosarcina acetivorans C2A	Q8TRU7	94.4%	Diamond
Saccharolobus solfataricus P2	Q9UXA8	94.0%	Diamond
Nakaseomyces glabratus CBS 138	Q6FTJ2	93.5%	Diamond
Eremothecium gossypii ATCC 10895	Q759R7	93.5%	Diamond
Pyrococcus furiosus DSM 3638	Q8TZZ8	93.4%	Diamond
Thermococcus onnurineus NA1	B6YSL3	93.1%	Diamond
Thermococcus kodakarensis KOD1	Q5JDJ0	93.1%	Diamond
Saccharomyces cerevisiae S288C	P14126	93.0%	Diamond
Thermococcus gammatolerans EJ3	C5A286	92.8%	Diamond
Pyrobaculum arsenaticum DSM 13514	A4WMH5	92.3%	Diamond
Pyrobaculum aerophilum str. IM2	Q8ZW52	92.3%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CJR7	92.2%	Diamond
Candida albicans SC5314	Q59LS1	91.8%	Diamond
Debaryomyces hansenii CBS767	Q6BXM5	91.8%	Diamond
Pyrobaculum calidifontis JCM 11548	A3MWI4	90.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MGAT3-AS1	ncRNA	104502417
TAB1	protein-coding	10454
SNORD43	snoRNA	26807
MGAT3	protein-coding	4248
MIEF1	protein-coding	54471
SYNGR1	protein-coding	9145
SNORD83B	snoRNA	116938
PDGFB	protein-coding	5155
SNORD83A	snoRNA	116937
SNORD139	snoRNA	116936
CBX7	protein-coding	23492

Protein

Protein identifiers

Large ribosomal subunit protein uL3 — P39023 (reviewed: P39023)

Alternative names: 60S ribosomal protein L3, HIV-1 TAR RNA-binding protein B

All UniProt accessions (6): B5MCW2, P39023, F8WCR1, G5E9G0, H7C3M2, H7C422

UniProt curated annotations — full annotation on UniProt →

Function. Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.

Subunit / interactions. Component of the large ribosomal subunit. Interacts with DHX33. Interacts with GRWD1.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Post-translational modifications. Constitutively monomethylated at His-245 by METTL18. Methylation at His-245 regulates translation elongation by slowing ribosome traversal on tyrosine codons: slower elongation provides enough time for proper folding of synthesized proteins and prevents cellular aggregation of tyrosine-rich proteins. It is not required for incorporation of RPL3 into ribosomes.

Similarity. Belongs to the universal ribosomal protein uL3 family.

RefSeq proteins (2): NP_000958, NP_001029025 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000597	Ribosomal_uL3	Family
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR019926	Ribosomal_uL3_CS	Conserved_site
IPR044892	Ribosomal_L3_dom_3_arc_sf	Homologous_superfamily
IPR045077	L3_arc_euk	Family

Pfam: PF00297

UniProt features (74 total): strand 24, helix 18, cross-link 9, modified residue 8, turn 7, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, sequence variant 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

showing 30 of 182 structures by resolution:

PDB	Title	Method	Resolution (Å)
8A3D	Human mature large subunit of the ribosome with eIF6 and homoharringtonine bound	ELECTRON MICROSCOPY	1.67
8GLP	mRNA decoding in human is kinetically and structurally distinct from bacteria (Consensus …	ELECTRON MICROSCOPY	1.67
8QYX	Human 60S ribosomal subunit	ELECTRON MICROSCOPY	1.78
8QOI	Structure of the human 80S ribosome at 1.9 A resolution - the molecular role of chemical …	ELECTRON MICROSCOPY	1.9
9O3W	Human 80S ribosome bound to IDB-001 stalled on MYC nascent chain	ELECTRON MICROSCOPY	1.9
8YOO	Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline	ELECTRON MICROSCOPY	2
9C3H	Structure of the CNOT3-bound human 80S ribosome with tRNA-ARG in the P-site.	ELECTRON MICROSCOPY	2
9PBE	In situ human 80S ribosome (composite map)	ELECTRON MICROSCOPY	2.19
9I2D	NMT1-NAC bound human RNC with 10 amino acid ARF1-linker	ELECTRON MICROSCOPY	2.19
8QFD	UFL1 E3 ligase bound 60S ribosome	ELECTRON MICROSCOPY	2.2
8YOP	Cryo-EM structure of the human 80S ribosome with 4 um Tigecycline	ELECTRON MICROSCOPY	2.2
9GUL	Structure of FLuc-XBP1u+ stalled human 60S ribosome nascent chain complex	ELECTRON MICROSCOPY	2.2
9O3V	Human 80S ribosome stalled on MYC nascent chain	ELECTRON MICROSCOPY	2.2
9O3Y	Human 80S ribosome bound to IDB-002 stalled on FPAK-containing nascent chain	ELECTRON MICROSCOPY	2.2
8JDK	Structure of the Human cytoplasmic Ribosome with human tRNA Asp(ManQ34) and mRNA(GAU)	ELECTRON MICROSCOPY	2.26
8G5Y	mRNA decoding in human is kinetically and structurally distinct from bacteria (IC state)	ELECTRON MICROSCOPY	2.29
9S3D	NAC bound human RNC with 58 amino acid ARF1-linker	ELECTRON MICROSCOPY	2.32
9MNC	Human 80S ribosome bound to small molecule SW393071	ELECTRON MICROSCOPY	2.33
9RPV	Structure of the ZAK-bound human disome	ELECTRON MICROSCOPY	2.35
9S3B	NMT1-NAC bound human RNC with 58 amino acid ARF1-linker - State 1	ELECTRON MICROSCOPY	2.38
8K2C	Cryo-EM structure of the human 80S ribosome with Tigecycline	ELECTRON MICROSCOPY	2.4
8XSX	Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA, SERBP1 and eEF2	ELECTRON MICROSCOPY	2.4
9SPF	CRYO-EM STRUCTURE OF HUMAN 80S RIBOSOME WITH A/P/E-SITE TRNA AND MRNA CONTAINING …	ELECTRON MICROSCOPY	2.4
9SPI	CRYO-EM STRUCTURE OF HUMAN 80S RIBOSOME WITH A/P/E-SITE TRNA AND MRNA CONTAINING URIDINE	ELECTRON MICROSCOPY	2.4
8JDL	Structure of the Human cytoplasmic Ribosome with human tRNA Tyr(GalQ34) and mRNA(UAU) …	ELECTRON MICROSCOPY	2.42
9PKD	In situ CHX and HHT treated 80S consensus ribosome	ELECTRON MICROSCOPY	2.42
9S3C	NMT1-NAC bound human RNC with 58 amino acid ARF1-linker - State 2	ELECTRON MICROSCOPY	2.42
8FKV	Human nucleolar pre-60S ribosomal subunit (State D1)	ELECTRON MICROSCOPY	2.47
9QLO	NMT1-NAC bound human RNC with full length ARF1 - State 1	ELECTRON MICROSCOPY	2.47
8FLE	Human nuclear pre-60S ribosomal subunit (State L2)	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P39023-F1	96.38	0.98

Human Protein Atlas

Protein class: Ribosomal proteins, Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoli

Antibody reliability (HPA): IH uncertain · IF supported

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 (17)

Type	Positions
N6-acetyllysine	366, 373, 136, 286, 294
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	39, 224, 226, 286, 366, 386, 393, 399
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	294
Phosphoserine	13, 304
Tele-methylhistidine	245

Mutagenesis-validated functional residues (1)

Position	Phenotype
246–249	no effect on methylation by mettl18.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 40; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

40 pathways:

ID	Pathway	Evidence
R-HSA-192823	Viral mRNA Translation ⚕	curated
R-HSA-72689	Formation of a pool of free 40S subunits	curated
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit	curated
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression	curated
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol	curated
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	curated
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	curated
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	curated
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-168255	Influenza Infection ⚕	—
R-HSA-168273	Influenza Viral RNA Transcription and Replication ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-72737	Cap-dependent Translation Initiation	—
R-HSA-9711097	Cellular response to starvation	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-1266738	Developmental Biology	—
R-HSA-156842	Eukaryotic Translation Elongation	—
R-HSA-72613	Eukaryotic Translation Initiation	—
R-HSA-72764	Eukaryotic Translation Termination	electronic
R-HSA-1430728	Metabolism	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-9675108	Nervous system development	—
R-HSA-927802	Nonsense-Mediated Decay (NMD)	—
R-HSA-156902	Peptide chain elongation	electronic
R-HSA-9010553	Regulation of expression of SLITs and ROBOs	electronic
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency	electronic
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	electronic
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane	electronic
R-HSA-2408522	Selenoamino acid metabolism	—
R-HSA-2408557	Selenocysteine synthesis	electronic
R-HSA-376176	Signaling by ROBO receptors	—
R-HSA-72766	Translation	—
R-HSA-72312	rRNA processing	—
R-HSA-8868773	rRNA processing in the nucleus and cytosol	—

MSigDB gene sets: 277 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, HORIUCHI_WTAP_TARGETS_DN, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GCM_NPM1, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, KONG_E2F3_TARGETS, GOBP_TRANSLATION, MAHAJAN_RESPONSE_TO_IL1A_DN

GO Biological Process (3): cytoplasmic translation (GO:0002181), translation (GO:0006412), spermatogenesis (GO:0007283)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Translation	3
Ribosome-associated quality control	3
Cap-dependent Translation Initiation	2
Nonsense-Mediated Decay (NMD)	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Signaling by ROBO receptors	1
Cellular response to starvation	1

GO top-level categories

27 GO namespaces:

Category	Terms
ribosome	2
intracellular membraneless organelle	2
cellular anatomical structure	2
translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
nucleic acid binding	1
structural molecule activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
cellular_component	1
extracellular vesicle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	high-throughput assay
cytosol	CC	direct assay
cytosolic large ribosomal subunit	CC	direct assay
cytosolic ribosome	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
nucleolus	CC	direct assay
nucleus	CC	high-throughput assay
protein-containing complex	CC	direct assay
RNA binding	MF	high-throughput assay
structural constituent of ribosome	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,312 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL3	MRPL3	P09001	832
RPL3	RPL4	P36578	769
RPL3	RPL5	P46777	743
RPL3	RPL12	P30050	727
RPL3	RPL6	Q02878	719
RPL3	RPS3	P23396	707
RPL3	RPS8	P09058	690
RPL3	RPL8	P25120	672
RPL3	RPL11	P25121	665
RPL3	RPL18	Q07020	665
RPL3	METTL18	O95568	662
RPL3	RPS2	P15880	659
RPL3	RPL7	P18124	656
RPL3	RPL14	P50914	656
RPL3	RPS19	P39019	642

IntAct

Human interaction partners of RPL3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 33 partners by confidence:

Partner	Interaction type	MIscore	Records
WFS1	physical association	0.560	3
SHANK3	physical association	0.550	1
AHNAK2	physical association	0.400	1
DCUN1D5	physical association	0.400	1
HSPA5	physical association	0.400	1
NDRG1	physical association	0.400	1
RPL9	physical association	0.400	1
E7	physical association	0.370	9
NUMB	physical association	0.370	1
SIK1	physical association	0.370	1
STXBP3	physical association	0.370	1
GTPBP10	association	0.350	1
MRPL21	association	0.350	1
MRPL34	association	0.350	1
ACTR6	physical association	0.000	1
ATG5	physical association	0.000	1
BCAR3	physical association	0.000	1
CDC42BPB	physical association	0.000	1
CNBP	physical association	0.000	1
EIF1B	physical association	0.000	1
EIF6	physical association	0.000	1
HLA-B	physical association	0.000	1
IKBKE	physical association	0.000	1
LYAR	physical association	0.000	1
MAGEB2	physical association	0.000	1
MAP3K1	physical association	0.000	1
MAP3K14	physical association	0.000	1
PRKAB1	physical association	0.000	1
PSTPIP1	physical association	0.000	1
SGK1	physical association	0.000	1

BioGRID (1,138 interactions; top human partners by supporting records in a sample of 600 records): EBNA1BP2 (Affinity Capture-MS; 4 records), NPM1 (Affinity Capture-MS; 4 records), RPL30 (Co-fractionation; 4 records), GLTSCR2 (Affinity Capture-MS; 3 records), NCL (Co-fractionation; 3 records), PPP1CC (Affinity Capture-MS; 3 records), PRR11 (Affinity Capture-MS; 3 records), RBM34 (Affinity Capture-MS; 3 records), RPL10 (Co-fractionation; 3 records), RPL14 (Affinity Capture-MS; 3 records), RPL18 (Co-fractionation; 3 records), RPL18A (Co-fractionation; 3 records), RPL26L1 (Co-fractionation; 3 records), RPL28 (Co-fractionation; 3 records), RPL37A (Co-fractionation; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
RPL3	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ Nop56p-associated pre-rRNA complex	104	LUC7L2, NCL, RPL27, RPL29, RPL39, RPL7, RPS23, RPS6, MYBBP1A, RPL21, RPL28, RPL5, RPS9, U2AF2, LYAR, RPL13, RPL23, RPL23A, RPL35A, RPL4, RPS24, HNRNPA1, EBNA1BP2, RPLP1, RPS17, U2AF1, DHX9, RPL30, SCYL2, RPL11, RPS11, NOLC1, RPL12, RPL14, RPL17, RPL19, RPL32, RPS13, RPS8, NOP58, RPL36A, RPLP2, RPS2, RPS29, SRP14, TCOF1, TUFM, ACTG2, RBM28, RPL10, RPL37A, RPS12, RPS7, TUBB1, BRIX1, DDX21, GNL3, IGF2BP1, ILF2, RPL10A, RPL15, RPLP0, EEF2, HNRNPU, NOP56, RPL26, RPL3, RPS14, RPS16, RSL1D1, ACTA2, EEF1A1, H1-3, RPL24, RPL6, RPL8, SRPK1, TOP1, FBL, HNRNPM, RPL13A, RPL31, RPL7A, RPS18, H1-10, ILF3, NPM1, RPS15A, TUBA1A, YBX1, H2BC14, PWP1, RPL18A, RPL22, RPL27A, RPS15, RPS3A, SLC25A5, NAP1L1, RPL18, RPL35, RPL36, RPL9, SNU13
Ribosome, cytoplasmic	80	RPS12, RPS27A, RPL12, RPSA, RPL24, RPL27A, RPL37, RPLP0, RPS15, RPS3A, RPL10, RPL15, RPL23A, RPL36A, RPS15A, RPS19, RPL17, RPL6, RPLP1, RPS23, RPS28, RPS6, RPL29, RPL35A, RPS4Y1, RPS7, RPS10, RPL13, RPL28, RPL3, RPL30, RPL36, RPS27, RPS9, RPL14, RPL26, RPS17, RPS2, RPL13A, RPL27, RPL35, RPL38, RPL41, RPS18, RPS26, RPL22, RPL4, RPL5, RPS11, UBA52, RPL18, RPL7A, RPL19, RPL37A, RPL8, RPS14, RPS20, FAU, RPL34, RPL7, RPS21, RPS25, RPS5, RPS13, RPS24, RPS29, RPS8, RPL39, RPL9, RPLP2, RPS3, RPL10A, RPL11, RPL18A, RPL23, RPL31, RPS16, RPS4X, RPL21, RPL32
60S ribosomal subunit, cytoplasmic	47	RPL27, RPL9, RPLP2, RPL17, RPL19, RPL5, RPL12, RPL13, RPL13A, RPL30, RPL35, RPL35A, RPL36, RPL6, RPL18, RPL23A, RPL28, RPL32, RPL37A, RPL38, RPL7, RPL8, RPL10A, RPL21, RPL23, RPL7A, RPLP0, RPL14, RPL27A, RPL29, RPL3, RPL37, RPL39, RPL15, RPL34, RPL36A, RPLP1, RPL10, RPL18A, RPL22, RPL24, RPL31, RPL4, RPL41, UBA52, RPL11, RPL26

Disease & clinical

Genetic variants

Variant evidence for RPL3: 75 ClinVar records (0 pathogenic / likely pathogenic); 9 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	3
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 682):

Position(s)	Effect	Δscore	Sites
22:39312985–39312986	acceptor_loss	1.0000	2
22:39313189–39313190	donor_loss	1.0000	3
22:39313311–39313312	acceptor_loss	1.0000	4
22:39313313	acceptor_gain	1.0000
22:39313319	acceptor_gain	1.0000
22:39313632–39313633	donor_loss	1.0000	5
22:39313730	acceptor_loss	1.0000
22:39314105–39314106	donor_loss	1.0000	3
22:39314209–39314210	acceptor_loss	1.0000	5
22:39314684–39314685	donor_loss	1.0000	3

AlphaMissense

2,006 missense substitutions predicted likely pathogenic (of 2,665 scored), across 380 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M53	9	0.990	0.999
D218	8	0.999	1.000
D308	8	0.998	0.999
D369	8	0.998	0.999
H245	8	0.995	0.999
H258	8	0.995	0.999
H3	8	0.994	0.998
H55	8	0.994	0.999
H276	8	0.992	0.999
F130	8	0.990	1.000
H165	8	0.988	0.998
D35	8	0.986	0.998
F320	8	0.985	1.000
F211	8	0.978	0.998
F367	8	0.976	1.000
F379	8	0.975	1.000
H11	8	0.968	0.994
H179	8	0.968	0.995
F106	8	0.966	0.998
F16	8	0.964	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:604163 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST004131_35	Inflammatory bowel disease	5e-24
GCST004132_113	Crohn’s disease	8e-21
GCST007446_9	vWF levels	6e-14
GCST005581_20	Primary biliary cirrhosis	1e-13
GCST004133_33	Ulcerative colitis	3e-10
GCST007445_22	Factor VIII levels	9e-9
GCST004302_11	Primary biliary cholangitis	3e-8
GCST007445_43	Factor VIII levels	2e-7
GCST007445_38	Factor VIII levels	2e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004630	factor VIII measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066907 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

48 potent at pChembl≥5 of 54 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.58	Kd	2639	nM	CHEMBL3752910
5.58	ED50	2639	nM	CHEMBL3752910
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

47 with measured affinity, of 209 total; 27 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149260: Binding affinity to human RPL3 incubated for 45 mins by Kinobead based pull down assay	kd	2.6389	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression	4
bisphenol A	decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Fluorouracil	decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
chloropicrin	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
pyrimidifen	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pyrachlostrobin	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1920845	Binding	Induction of ribosome to readthrough in human A-T lymphoblastoid cells assessed as ATM ser1981 autophosphorylation at 30 uM after 4 days by PTT-ELISA assay	Synthesis and evaluation of compounds that induce readthrough of premature termination codons. — *Bioorg Med Chem Lett*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RPL3 across ~30M SureChEMBL compounds — explore on Sugi Predict.