RPL27A

Summary

RPL27A (ribosomal protein L27a, HGNC:10329) is a protein-coding gene on chromosome 11p15.4, encoding Large ribosomal subunit protein uL15 (P46776). Component of the large ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer 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 L15P 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, multiple processed pseudogenes derived from this gene are dispersed through the genome.

Source: NCBI Gene 6157 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 22 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_000990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10329
Approved symbol	RPL27A
Name	ribosomal protein L27a
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	L27A, uL15
Ensembl gene	ENSG00000166441
Ensembl biotype	protein_coding
OMIM	603637
Entrez	6157

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000314138, ENST00000524496, ENST00000525981, ENST00000526562, ENST00000529227, ENST00000530022, ENST00000530585, ENST00000530913, ENST00000531102, ENST00000531978, ENST00000532359, ENST00000534599, ENST00000921544

RefSeq mRNA: 1 — MANE Select: NM_000990 NM_000990

CCDS: CCDS7790

Canonical transcript exons

ENST00000314138 — 5 exons

Exon	Start	End
ENSE00001431941	8685678	8689872
ENSE00002165367	8682792	8682816
ENSE00003498786	8683202	8683265
ENSE00003629022	8684006	8684081
ENSE00003692691	8684718	8684892

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 205.2508 / max 1467.1503, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112942	203.0453	1825
112943	0.9774	597
112944	0.6889	370
112946	0.5392	348

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	99.88	gold quality
adenohypophysis	UBERON:0002196	99.88	gold quality
ganglionic eminence	UBERON:0004023	99.88	gold quality
embryo	UBERON:0000922	99.87	gold quality
left lobe of thyroid gland	UBERON:0001120	99.87	gold quality
left ovary	UBERON:0002119	99.87	gold quality
mucosa of transverse colon	UBERON:0004991	99.87	gold quality
granulocyte	CL:0000094	99.86	gold quality
stromal cell of endometrium	CL:0002255	99.86	gold quality
endocervix	UBERON:0000458	99.86	gold quality
right lobe of thyroid gland	UBERON:0001119	99.86	gold quality
right uterine tube	UBERON:0001302	99.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.86	gold quality
body of uterus	UBERON:0009853	99.86	gold quality
ectocervix	UBERON:0012249	99.86	gold quality
mucosa of stomach	UBERON:0001199	99.85	gold quality
skin of abdomen	UBERON:0001416	99.85	gold quality
right ovary	UBERON:0002118	99.85	gold quality
right lung	UBERON:0002167	99.85	gold quality
ventricular zone	UBERON:0003053	99.85	gold quality
left uterine tube	UBERON:0001303	99.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.84	gold quality
lower esophagus mucosa	UBERON:0035834	99.84	gold quality
transverse colon	UBERON:0001157	99.83	gold quality
body of stomach	UBERON:0001161	99.83	gold quality
minor salivary gland	UBERON:0001830	99.83	gold quality
descending thoracic aorta	UBERON:0002345	99.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.83	gold quality
cortical plate	UBERON:0005343	99.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.83	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	4264.29
E-CURD-122	yes	88.11
E-CURD-88	yes	64.48
E-MTAB-9221	yes	54.01
E-CURD-112	yes	42.49
E-MTAB-6678	yes	34.78
E-HCAD-31	yes	19.37
E-MTAB-10042	yes	10.92
E-HCAD-35	yes	9.75
E-HCAD-36	no	6260.78
E-CURD-95	no	5543.18
E-CURD-79	no	5138.61
E-GEOD-114530	no	4977.90
E-GEOD-124263	no	4521.59
E-MTAB-8060	no	3441.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

98 targeting RPL27A, 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-4713-3P	100.00	65.92	505
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• RPL27A overexpression, despite showing no significant effects on p53 mRNA levels, did in fact enhance cellular proliferation. In normal CD34+ cells, RPL27A knockdown preferentially blocked erythroid proliferation and differentiation. (PMID:27374104)
• tRF-19-W4PU732S promotes breast cancer cell malignant activity by targeting inhibition of RPL27A (ribosomal protein-L27A). (PMID:35030975)
• High expression of RPL27A predicts poor prognosis in patients with hepatocellular carcinoma. (PMID:37474947)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rpl27a	ENSMUSG00000046364
drosophila_melanogaster	RpL27A	FBGN0285948
caenorhabditis_elegans	Y37E3.8	WBGENE00021350

Protein

Protein identifiers

Large ribosomal subunit protein uL15 — P46776 (reviewed: P46776)

Alternative names: 60S ribosomal protein L27a

All UniProt accessions (6): E9PJD9, E9PKT2, E9PLL6, E9PLX7, P46776, H0YF34

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.

Post-translational modifications. Hydroxylated on His-39 by MINA.

Similarity. Belongs to the universal ribosomal protein uL15 family.

RefSeq proteins (1): NP_000981* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001196	Ribosomal_uL15_CS	Conserved_site
IPR021131	Ribosomal_uL15/eL18	Domain
IPR027386	Rbsml_uL15_N	Homologous_superfamily
IPR030878	Ribosomal_uL15	Family
IPR036227	Ribosomal_uL15/eL18_sf	Homologous_superfamily

Pfam: PF00828

UniProt features (8 total): modified residue 5, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

193 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
4BXF	X-RAY DIFFRACTION	2.05
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
9O3V	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
8FKV	ELECTRON MICROSCOPY	2.47
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46776-F1	93.99	0.88

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 (5): 39, 47, 55, 68, 110

Function

Pathways and Gene Ontology

Reactome pathways

17 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-9629569	Protein hydroxylation
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: 233 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, DORSAM_HOXA9_TARGETS_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_151, GNF2_TPT1, GCM_NPM1, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION

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 (11): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), synapse (GO:0045202), ribosome (GO:0005840), large ribosomal subunit (GO:0015934), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-12 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
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	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
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
cell junction	1
intracellular membraneless organelle	1
ribosomal subunit	1
protein-containing complex	1

Protein interactions and networks

STRING

3815 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL27A	RPS9	P46781	957
RPL27A	RPL28	P46779	954
RPL27A	RPL21	P46778	952
RPL27A	RPS29	P30054	945
RPL27A	RPS10	P46783	941
RPL27A	RPS5	P46782	928
RPL27A	RPL5	P46777	918
RPL27A	RPL6	Q02878	782
RPL27A	RPL14	P50914	744
RPL27A	RPL8	P25120	736
RPL27A	RPL4	P36578	731
RPL27A	RPS16	P17008	730
RPL27A	RIOX2	Q8IUF8	714
RPL27A	RPS14	P06366	713
RPL27A	RPS18	P25232	709

IntAct

253 interactions, top by confidence:

A	B	Type	Score
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
CAND1	RPL27A	psi-mi:“MI:0915”(physical association)	0.560
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
RPL13	RPLP1	psi-mi:“MI:0914”(association)	0.530
GTF2F2	RPL27A	psi-mi:“MI:0915”(physical association)	0.520
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
RIOX2	RPL27A	psi-mi:“MI:0407”(direct interaction)	0.440
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
ACACA	RPL27A	psi-mi:“MI:0915”(physical association)	0.400
TRMT11	RPL27A	psi-mi:“MI:0915”(physical association)	0.400
CDKN1B	RPL27A	psi-mi:“MI:0915”(physical association)	0.400
EML5	RPL27A	psi-mi:“MI:0915”(physical association)	0.400
PAK1	RPL27A	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (670): RPL27A (Affinity Capture-MS), SIAH1 (Two-hybrid), RPL27A (Affinity Capture-MS), RPL27A (Affinity Capture-MS), RPL27A (Affinity Capture-MS), RPL27A (Affinity Capture-MS), RPL27A (Affinity Capture-MS), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL15 (Co-fractionation), RPL17 (Co-fractionation), RPL27A (Co-fractionation), RPL27A (Co-fractionation), RPL27A (Co-fractionation), RPL27A (Co-fractionation)

ESM2 similar proteins: A5JSS2, A6H769, E2RKA8, G1SHQ2, G1SNY0, G1SQH0, G1SVB0, O09167, O14602, P12749, P14115, P18445, P20280, P30742, P41567, P46776, P46778, P47813, P47832, P49171, P49666, P61251, P61254, P61255, P61256, P61257, P62081, P62082, P62083, P62854, P62855, P62856, P62910, P62911, P62912, Q3SZQ6, Q4R723, Q56JV1, Q56K03, Q5E938

Diamond homologs: A0A1D8PSC5, A1RT57, A3DNC9, A3MUZ1, A4FVT7, A4WM07, A6UQ66, A6UWW0, A6VH07, A9A9P2, A9BFZ9, G1SNY0, O01358, O15883, O26133, O62581, P02406, P08978, P14032, P14115, P18445, P36585, P41092, P46776, P47830, P47831, P48160, P48161, P49637, P54047, P57728, P78987, Q00454, Q27021, Q29333, Q2NFX9, Q4R723, Q56K03, Q5R1X0, Q5REY2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL27A	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 188 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	21	14.5×	4e-16
Eukaryotic Translation Termination	17	14.1×	3e-13
Peptide chain elongation	16	14.0×	1e-12
Viral mRNA Translation	16	14.0×	1e-12
Formation of a pool of free 40S subunits	18	13.9×	9e-14
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	16	13.8×	2e-12
GTP hydrolysis and joining of the 60S ribosomal subunit	20	13.8×	4e-15
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	17	13.8×	4e-13

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	19	20.8×	4e-17
stress granule assembly	5	17.8×	1e-03
ribosomal large subunit biogenesis	6	15.7×	4e-04
translational initiation	7	14.8×	9e-05
mRNA stabilization	6	13.0×	1e-03
translation	21	12.8×	9e-15
negative regulation of translation	11	12.8×	4e-07
rRNA processing	12	10.1×	8e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3444 predictions. Top by Δscore:

Variant	Effect	Δscore
11:8683266:G:C	donor_loss	1.0000
11:8683266:G:GG	donor_gain	1.0000
11:8684077:AAATA:A	donor_gain	1.0000
11:8684078:AATA:A	donor_gain	1.0000
11:8684079:ATA:A	donor_gain	1.0000
11:8684079:ATAG:A	donor_loss	1.0000
11:8684080:TA:T	donor_gain	1.0000
11:8684080:TAGT:T	donor_loss	1.0000
11:8684081:AG:A	donor_loss	1.0000
11:8684082:G:GG	donor_gain	1.0000
11:8684082:GTAA:G	donor_loss	1.0000
11:8684716:A:AG	acceptor_gain	1.0000
11:8684717:G:GA	acceptor_gain	1.0000
11:8684717:GC:G	acceptor_gain	1.0000
11:8684717:GCC:G	acceptor_gain	1.0000
11:8684891:CGGTA:C	donor_loss	1.0000
11:8684892:GGTAA:G	donor_loss	1.0000
11:8684893:GTAA:G	donor_loss	1.0000
11:8684894:TAA:T	donor_loss	1.0000
11:8685757:C:G	donor_gain	1.0000
11:8685763:A:T	donor_gain	1.0000
11:8685769:T:TG	donor_gain	1.0000
11:8685819:G:GT	donor_gain	1.0000
11:8694131:C:CC	acceptor_gain	1.0000
11:8694132:T:A	acceptor_loss	1.0000
11:8694139:C:CT	acceptor_gain	1.0000
11:8694139:C:T	acceptor_gain	1.0000
11:8694140:A:T	acceptor_gain	1.0000
11:8695458:CTTA:C	donor_loss	1.0000
11:8695459:TTA:T	donor_loss	1.0000

AlphaMissense

968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:8683233:G:T	R12M	0.999
11:8683235:G:C	G13R	0.998
11:8683250:G:C	G18R	0.997
11:8683251:G:A	G18D	0.997
11:8683257:G:A	G20D	0.997
11:8684809:T:A	W79R	0.997
11:8684809:T:C	W79R	0.997
11:8685724:T:A	V122D	0.997
11:8683233:G:C	R12T	0.996
11:8683236:G:A	G13D	0.996
11:8683236:G:T	G13V	0.996
11:8683244:A:C	S16R	0.996
11:8683246:C:A	S16R	0.996
11:8683246:C:G	S16R	0.996
11:8683251:G:T	G18V	0.996
11:8683256:G:C	G20R	0.996
11:8683257:G:T	G20V	0.996
11:8685691:T:A	V111D	0.996
11:8685730:T:A	V124E	0.996
11:8683234:G:C	R12S	0.995
11:8683234:G:T	R12S	0.995
11:8684035:G:C	G33R	0.995
11:8684036:G:A	G33D	0.995
11:8684036:G:T	G33V	0.995
11:8684045:G:A	G36D	0.995
11:8684063:G:C	R42P	0.995
11:8684731:T:C	F53L	0.995
11:8684733:T:A	F53L	0.995
11:8684733:T:G	F53L	0.995
11:8684792:T:A	V73D	0.995

dbSNP variants (sampled 300 via entrez): RS1000036465 (11:8681402 G>A), RS1000488056 (11:8681369 G>A,C), RS1001394543 (11:8684284 G>A), RS1001578248 (11:8681132 G>GA), RS1002378478 (11:8685051 G>C,T), RS1002965052 (11:8687518 G>A), RS1003016787 (11:8687743 C>T), RS1003151158 (11:8681867 G>A,C), RS1003393023 (11:8682578 G>A), RS1003447583 (11:8685994 G>A), RS1003787109 (11:8686440 A>T), RS1003957078 (11:8683743 T>C), RS1003982366 (11:8681919 T>G), RS1004215475 (11:8680976 G>A), RS1004333254 (11:8681687 A>G)

Disease associations

OMIM: gene MIM:603637 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000830_35	Body mass index	3.000000e-09
GCST001953_23	Obesity	1.000000e-11
GCST004557_17	Body mass index	2.000000e-10
GCST004557_200	Body mass index	2.000000e-09
GCST004557_229	Body mass index	9.000000e-11
GCST004557_99	Body mass index	1.000000e-09
GCST004558_14	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-09
GCST004558_149	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-10
GCST004558_171	Body mass index (joint analysis main effects and physical activity interaction)	8.000000e-09
GCST004558_97	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-08
GCST004559_12	Body mass index in physically active individuals	2.000000e-08
GCST004559_130	Body mass index in physically active individuals	1.000000e-07
GCST004559_50	Body mass index in physically active individuals	1.000000e-07
GCST004559_92	Body mass index in physically active individuals	1.000000e-08
GCST005950_10	Body mass index x sex x age interaction (4df test)	6.000000e-11
GCST005951_51	Body mass index	8.000000e-11
GCST005953_4	Body mass index (age <50)	4.000000e-11
GCST010136_6	Fruit consumption	9.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066897 (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 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
5.55	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
5.23	Kd	5946	nM	CHEMBL3752910
5.23	ED50	5946	nM	CHEMBL3752910
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
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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149258: Binding affinity to human RPL27A incubated for 45 mins by Kinobead based pull down assay	kd	5.9465	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	5
sodium arsenite	decreases expression, increases activity	2
perfluorooctanoic acid	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, increases expression	2
epigallocatechin gallate	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Caffeine	affects phosphorylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
bis(tri-n-butyltin)oxide	decreases expression	1
deoxynivalenol	decreases expression	1
methylselenic acid	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
phenanthrene	decreases expression	1
perfluorodecanoic acid	decreases 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)

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