RPL28

Summary

RPL28 (ribosomal protein L28, HGNC:10330) is a protein-coding gene on chromosome 19q13.42, encoding Large ribosomal subunit protein eL28 (P46779). Component of the large ribosomal subunit. It is a selective cancer dependency (DepMap: 89.9% of cell lines).

Ribosomes, the organelles 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 L28E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 6158 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 89.9% of screened cell lines
• MANE Select transcript: NM_000991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10330
Approved symbol	RPL28
Name	ribosomal protein L28
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43307, L28, eL28
Ensembl gene	ENSG00000108107
Ensembl biotype	protein_coding
OMIM	603638
Entrez	6158

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 28 protein_coding, 2 retained_intron

ENST00000344063, ENST00000426763, ENST00000428193, ENST00000431533, ENST00000558131, ENST00000558752, ENST00000558815, ENST00000559463, ENST00000560055, ENST00000560583, ENST00000560881, ENST00000889917, ENST00000889918, ENST00000929176, ENST00000929177, ENST00000929178, ENST00000929179, ENST00000929180, ENST00000929181, ENST00000929182, ENST00000929183, ENST00000929184, ENST00000929185, ENST00000929186, ENST00000929187, ENST00000929188, ENST00000929189, ENST00000929190, ENST00000967861, ENST00000967862

RefSeq mRNA: 6 — MANE Select: NM_000991 NM_000991, NM_001136134, NM_001136135, NM_001136136, NM_001136137, NM_001363697

CCDS: CCDS12924, CCDS46189, CCDS46190, CCDS46191, CCDS46192, CCDS86809

Canonical transcript exons

ENST00000344063 — 5 exons

Exon	Start	End
ENSE00000699559	55386570	55386693
ENSE00001052644	55388243	55392085
ENSE00003537228	55387930	55388048
ENSE00003571849	55386350	55386438
ENSE00003900662	55385932	55385965

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2684.4338 / max 14567.5130, expressed in 1829 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177608	2682.7481	1829
177609	1.6857	928

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	99.96	gold quality
superficial temporal artery	UBERON:0001614	99.94	gold quality
oral cavity	UBERON:0000167	99.93	gold quality
endometrium epithelium	UBERON:0004811	99.93	gold quality
upper leg skin	UBERON:0004262	99.92	gold quality
skin of hip	UBERON:0001554	99.91	gold quality
trabecular bone tissue	UBERON:0002483	99.91	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.91	gold quality
lower esophagus mucosa	UBERON:0035834	99.91	gold quality
stromal cell of endometrium	CL:0002255	99.89	gold quality
penis	UBERON:0000989	99.89	gold quality
mammalian vulva	UBERON:0000997	99.89	gold quality
caput epididymis	UBERON:0004358	99.89	gold quality
corpus epididymis	UBERON:0004359	99.89	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.89	gold quality
lower lobe of lung	UBERON:0008949	99.89	gold quality
colonic mucosa	UBERON:0000317	99.87	gold quality
right uterine tube	UBERON:0001302	99.86	gold quality
granulocyte	CL:0000094	99.85	gold quality
pituitary gland	UBERON:0000007	99.85	gold quality
ileal mucosa	UBERON:0000331	99.85	gold quality
adenohypophysis	UBERON:0002196	99.85	gold quality
cartilage tissue	UBERON:0002418	99.85	gold quality
middle frontal gyrus	UBERON:0002702	99.85	gold quality
jejunal mucosa	UBERON:0000399	99.84	gold quality
seminal vesicle	UBERON:0000998	99.84	gold quality
nipple	UBERON:0002030	99.84	gold quality
spleen	UBERON:0002106	99.84	gold quality
cauda epididymis	UBERON:0004360	99.84	gold quality
zone of skin	UBERON:0000014	99.83	gold quality

Single-cell (SCXA)

Detected in 38 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	10680.76
E-CURD-88	yes	8658.27
E-MTAB-6678	yes	885.51
E-CURD-122	yes	100.47
E-MTAB-9221	yes	55.17
E-HCAD-9	yes	33.51
E-MTAB-9543	yes	19.44
E-HCAD-35	yes	10.64
E-GEOD-130148	yes	8.79
E-GEOD-137537	yes	5.78
E-HCAD-31	yes	4.92
E-MTAB-8142	no	9788.11
E-HCAD-36	no	7739.14
E-MTAB-6653	no	7683.58
E-MTAB-8530	no	7625.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting RPL28, 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-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4306	99.72	70.50	3630

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• 60S ribosomal proteins L6 (RPL6) and RPL28, which are adjacent on the ribosome, play opposite roles in generating an influenza A virus-encoded peptide. Depleting RPL6 decreases ubiquitin-dependent peptide presentation, whereas depleting RPL28 increases ubiquitin-dependent and -independent peptide presentation. (PMID:30712990)
• Germline variability and tumor expression level of ribosomal protein gene RPL28 are associated with survival of metastatic colorectal cancer patients. (PMID:31506518)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl28	ENSDARG00000005791
mus_musculus	Rpl28	ENSMUSG00000030432
rattus_norvegicus	Rpl28l2	ENSRNOG00000061441
drosophila_melanogaster	RpL28	FBGN0035422
caenorhabditis_elegans		WBGENE00004442

Protein

Protein identifiers

Large ribosomal subunit protein eL28 — P46779 (reviewed: P46779)

Alternative names: 60S ribosomal protein L28

All UniProt accessions (4): P46779, H0YKD8, H0YLP6, H0YMF4

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.

Subcellular location. Cytoplasm.

Similarity. Belongs to the eukaryotic ribosomal protein eL28 family.

Isoforms (5)

UniProt ID	Names	Canonical?
P46779-1	1	yes
P46779-2	2
P46779-3	3
P46779-4	4
P46779-5	5

RefSeq proteins (6): NP_000982, NP_001129606, NP_001129607, NP_001129608, NP_001129609, NP_001350626 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002672	Ribosomal_eL28	Family
IPR029004	Ribosomal_eL28/Mak16	Domain

Pfam: PF01778

UniProt features (13 total): splice variant 4, sequence conflict 2, modified residue 2, cross-link 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

192 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8A3D	ELECTRON MICROSCOPY	1.67
8GLP	ELECTRON MICROSCOPY	1.67
8QYX	ELECTRON MICROSCOPY	1.78
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8QFD	ELECTRON MICROSCOPY	2.2
8YOP	ELECTRON MICROSCOPY	2.2
9GUL	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
7OW7	ELECTRON MICROSCOPY	2.4
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5
8FKW	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46779-F1	92.59	0.87

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 (4): 2, 115, 58, 65

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-192823	Viral mRNA Translation
R-HSA-2408557	Selenocysteine synthesis
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA

MSigDB gene sets: 279 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, NEBEN_AML_WITH_FLT3_OR_NRAS_DN, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION, GGAANCGGAANY_UNKNOWN, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (2): cytoplasmic translation (GO:0002181), translation (GO:0006412)

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

GO Cellular Component (12): cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), dendrite (GO:0030425), cytoplasmic ribonucleoprotein granule (GO:0036464), cell body (GO:0044297), synapse (GO:0045202), extracellular exosome (GO:0070062), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Ribosome-associated quality control	3
Translation	2
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

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ribosome	2
cytoplasm	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
nucleic acid binding	1
structural molecule activity	1
binding	1
intracellular anatomical structure	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
neuron projection	1
dendritic tree	1
ribonucleoprotein granule	1
cell junction	1
extracellular vesicle	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL28	RPL21	P46778	959
RPL28	RPL27A	P46776	954
RPL28	RPS5	P46782	953
RPL28	RPS9	P46781	938
RPL28	RPS29	P30054	934
RPL28	RPS10	P46783	929
RPL28	RPL5	P46777	913
RPL28	RPL18	Q07020	776
RPL28	RPL4	P36578	768
RPL28	RPL11	P25121	763
RPL28	RPS20	P17075	744
RPL28	RPS14	P06366	735
RPL28	RPL27	P08526	719
RPL28	RPS13	P19116	694
RPL28	RPL36	Q9Y3U8	688

IntAct

230 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
RPL28	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.780
CCNDBP1	RPL28	psi-mi:“MI:0915”(physical association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DCC	NTN1	psi-mi:“MI:0914”(association)	0.700
RPL28	RPL4	psi-mi:“MI:0915”(physical association)	0.670
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
RPL7A	NOP56	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
APP	RPL28	psi-mi:“MI:0915”(physical association)	0.560
RPL28	MAGEB2	psi-mi:“MI:0914”(association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530

BioGRID (677): RPL28 (Affinity Capture-MS), RPL28 (Affinity Capture-MS), CCNDBP1 (Two-hybrid), RPL28 (Affinity Capture-MS), RPL28 (Affinity Capture-MS), RPL28 (Affinity Capture-MS), RPL23A (Co-fractionation), RPL28 (Co-fractionation), RPL28 (Co-fractionation), RPL28 (Co-fractionation), RPL28 (Co-fractionation), RPL28 (Co-fractionation), RPL28 (Co-fractionation), RPL28 (Co-fractionation), RPL28 (Co-fractionation)

ESM2 similar proteins: D0VWQ3, G1T6D1, G1TFE0, G1U7L1, P02412, P09897, P12001, P17702, P35980, P40590, P41098, P41105, P46779, P61367, P61368, P61369, P62829, P62830, P62831, P62832, P69090, P69091, Q07020, Q08200, Q3T057, Q3T0L7, Q4R5H8, Q5E973, Q5REU2, Q6P1L8, Q6PC14, Q6QMZ8, Q7T2N4, Q7T2N5, Q7T3M9, Q7T3N1, Q7T3N2, Q7T3N3, Q7T3N4, Q7T3N6

Diamond homologs: G1U7L1, O00822, O14069, O82204, P17702, P41105, P46779, P46780, Q21930, Q3T0L7, Q962T2, Q9GS21, Q9M0E2, Q9VZS5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL28	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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
SRP-dependent cotranslational protein targeting to membrane	23	18.9×	1e-20
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	19	18.3×	9e-17
Peptide chain elongation	17	17.7×	4e-15
Viral mRNA Translation	17	17.7×	4e-15
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	17	17.5×	4e-15
Response of EIF2AK4 (GCN2) to amino acid deficiency	19	17.3×	2e-16
Selenocysteine synthesis	17	16.8×	7e-15
Eukaryotic Translation Termination	17	16.8×	7e-15

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	20	23.1×	4e-19
ribosomal large subunit biogenesis	8	22.2×	6e-07
rRNA processing	15	13.3×	1e-10
ribosomal small subunit biogenesis	9	12.8×	7e-06
translation	19	12.2×	7e-13
regulation of signal transduction by p53 class mediator	5	12.0×	6e-03
translational initiation	5	11.2×	7e-03
negative regulation of translation	8	9.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

836 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55386345:CGCA:C	acceptor_loss	1.0000
19:55386346:GCAG:G	acceptor_loss	1.0000
19:55386347:CA:C	acceptor_loss	1.0000
19:55386348:A:AG	acceptor_gain	1.0000
19:55386348:A:AT	acceptor_loss	1.0000
19:55386348:AGCC:A	acceptor_gain	1.0000
19:55386349:G:GT	acceptor_gain	1.0000
19:55386349:GC:G	acceptor_gain	1.0000
19:55386349:GCC:G	acceptor_gain	1.0000
19:55386349:GCCG:G	acceptor_gain	1.0000
19:55386349:GCCGC:G	acceptor_gain	1.0000
19:55386417:GAA:G	donor_gain	1.0000
19:55386434:GCACT:G	donor_gain	1.0000
19:55386435:CACT:C	donor_gain	1.0000
19:55386436:ACT:A	donor_gain	1.0000
19:55386437:CT:C	donor_gain	1.0000
19:55386437:CTGTA:C	donor_loss	1.0000
19:55386438:TGTA:T	donor_loss	1.0000
19:55386439:G:GG	donor_gain	1.0000
19:55386439:GTA:G	donor_loss	1.0000
19:55386440:T:G	donor_loss	1.0000
19:55386556:C:CA	acceptor_gain	1.0000
19:55386566:CCAG:C	acceptor_loss	1.0000
19:55386568:A:AG	acceptor_gain	1.0000
19:55386568:A:G	acceptor_loss	1.0000
19:55386568:AG:A	acceptor_gain	1.0000
19:55386569:G:C	acceptor_loss	1.0000
19:55386569:G:GT	acceptor_gain	1.0000
19:55386569:GG:G	acceptor_gain	1.0000
19:55386569:GGA:G	acceptor_gain	1.0000

AlphaMissense

896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55386376:T:A	W7R	0.999
19:55386376:T:C	W7R	0.999
19:55386613:G:A	G42E	0.999
19:55388247:C:A	A110D	0.999
19:55388259:C:A	A114D	0.999
19:55386378:G:C	W7C	0.998
19:55386378:G:T	W7C	0.998
19:55386403:T:C	F16L	0.998
19:55386405:C:A	F16L	0.998
19:55386405:C:G	F16L	0.998
19:55386433:A:C	S26R	0.998
19:55386435:C:A	S26R	0.998
19:55386435:C:G	S26R	0.998
19:55386581:C:A	N31K	0.998
19:55386581:C:G	N31K	0.998
19:55386597:T:C	S37P	0.998
19:55386611:C:A	N41K	0.998
19:55386611:C:G	N41K	0.998
19:55386612:G:A	G42R	0.998
19:55386612:G:C	G42R	0.998
19:55388041:T:C	L106P	0.998
19:55388256:G:T	R113M	0.998
19:55388257:G:C	R113S	0.998
19:55388257:G:T	R113S	0.998
19:55386583:T:G	L32W	0.997
19:55386596:T:A	N36K	0.997
19:55386596:T:G	N36K	0.997
19:55386613:G:T	G42V	0.997
19:55386634:T:A	V49E	0.997
19:55386640:T:A	V51E	0.997

dbSNP variants (sampled 300 via entrez): RS1000045314 (19:55402794 C>T), RS1000121465 (19:55386972 C>A,T), RS1000302654 (19:55386249 T>G), RS1000355646 (19:55386454 A>C,G,T), RS1000594492 (19:55385528 A>C), RS1000673218 (19:55394508 G>A,C), RS1000907355 (19:55393794 G>A,C,T), RS1000939876 (19:55389601 G>A), RS1000956614 (19:55389899 C>T), RS1001156010 (19:55389495 C>G), RS1001210042 (19:55400239 C>T), RS1001266663 (19:55403558 A>C), RS1001327065 (19:55398454 C>T), RS1001394011 (19:55395770 T>G), RS1001394835 (19:55398547 A>C,G)

Disease associations

OMIM: gene MIM:603638 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90011894_13	Retinitis pigmentosa	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066894 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

48 potent at pChembl≥5 of 52 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.26	Kd	55.2	nM	CHEMBL5653589
7.26	ED50	55.2	nM	CHEMBL5653589
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
5.55	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 208 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149259: Binding affinity to human RPL28 incubated for 45 mins by Kinobead based pull down assay	kd	0.0552	uM
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
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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases activity, increases expression	4
bisphenol A	decreases expression	3
Valproic Acid	affects expression, increases methylation	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
methylparaben	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
phenanthrene	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
pyrimidifen	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
thifluzamide	increases expression	1
abrine	decreases expression	1

ChEMBL screening assays

91 unique, capped per target: 91 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ZD04	Mel 05.18	Cancer cell line	Male

Clinical trials (associated diseases)

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