RPL23A

Summary

RPL23A (ribosomal protein L23a, HGNC:10317) is a protein-coding gene on chromosome 17q11.2, encoding Large ribosomal subunit protein uL23 (P62750). 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 L23P family of ribosomal proteins. It is located in the cytoplasm. The protein may be one of the target molecules involved in mediating growth inhibition by interferon. In yeast, the corresponding protein binds to a specific site on the 26S rRNA. This gene is co-transcribed with the U42A, U42B, U101A, and U101B small nucleolar RNA genes, which are located in its third, first, second, and fourth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6147 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 28 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_000984

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10317
Approved symbol	RPL23A
Name	ribosomal protein L23a
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	L23A, uL23
Ensembl gene	ENSG00000198242
Ensembl biotype	protein_coding
OMIM	602326
Entrez	6147

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000355731, ENST00000394935, ENST00000394938, ENST00000422514, ENST00000472628, ENST00000496182, ENST00000578181, ENST00000580755, ENST00000582736, ENST00000940449, ENST00000940450

RefSeq mRNA: 1 — MANE Select: NM_000984 NM_000984

CCDS: CCDS11241

Canonical transcript exons

ENST00000422514 — 5 exons

Exon	Start	End
ENSE00001399932	28719985	28720030
ENSE00001846391	28723867	28724359
ENSE00002760128	28723571	28723640
ENSE00003569228	28722723	28722899
ENSE00003651969	28720707	28720890

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7042 / max 221.5980, expressed in 1802 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160055	17.2805	1792
160057	2.6045	1023
160056	0.8192	421

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.85	gold quality
ovary	UBERON:0000992	99.84	gold quality
calcaneal tendon	UBERON:0003701	99.84	gold quality
endocervix	UBERON:0000458	99.83	gold quality
right uterine tube	UBERON:0001302	99.82	gold quality
right ovary	UBERON:0002118	99.82	gold quality
uterine cervix	UBERON:0000002	99.81	gold quality
ectocervix	UBERON:0012249	99.80	gold quality
pituitary gland	UBERON:0000007	99.79	gold quality
skin of abdomen	UBERON:0001416	99.79	gold quality
fallopian tube	UBERON:0003889	99.79	gold quality
body of uterus	UBERON:0009853	99.79	gold quality
granulocyte	CL:0000094	99.78	gold quality
zone of skin	UBERON:0000014	99.78	gold quality
colonic epithelium	UBERON:0000397	99.78	gold quality
skin of leg	UBERON:0001511	99.78	gold quality
adenohypophysis	UBERON:0002196	99.78	gold quality
left uterine tube	UBERON:0001303	99.77	gold quality
popliteal artery	UBERON:0002250	99.77	gold quality
descending thoracic aorta	UBERON:0002345	99.77	gold quality
prostate gland	UBERON:0002367	99.77	gold quality
tonsil	UBERON:0002372	99.77	gold quality
ganglionic eminence	UBERON:0004023	99.77	gold quality
thoracic mammary gland	UBERON:0005200	99.77	gold quality
tibial artery	UBERON:0007610	99.77	gold quality
bone marrow cell	CL:0002092	99.76	gold quality
lymph node	UBERON:0000029	99.76	gold quality
vagina	UBERON:0000996	99.76	gold quality
right coronary artery	UBERON:0001625	99.76	gold quality
left coronary artery	UBERON:0001626	99.76	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	8287.16
E-HCAD-9	yes	5308.30
E-MTAB-9067	yes	3848.36
E-MTAB-8142	yes	156.94
E-CURD-122	yes	104.72
E-CURD-46	yes	80.52
E-CURD-88	yes	66.14
E-MTAB-9221	yes	56.87
E-MTAB-6678	yes	47.17
E-GEOD-135922	yes	27.54
E-CURD-112	yes	27.08
E-MTAB-10042	yes	16.56
E-MTAB-7316	yes	14.32
E-HCAD-35	yes	9.12
E-GEOD-137537	yes	6.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

31 targeting RPL23A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-5571-3P	97.80	66.07	640
HSA-MIR-3936	97.64	64.47	732

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 1)

• HERC3 directly targets RPL23A for ubiquitination degradation and further regulates Colorectal Cancer proliferation and the cell cycle. (PMID:35637966)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl23a	ENSDARG00000006316
mus_musculus	Rpl23a	ENSMUSG00000058546
rattus_norvegicus	Rpl23al9	ENSRNOG00000029859
rattus_norvegicus	Rpl23a	ENSRNOG00000032148
caenorhabditis_elegans		WBGENE00004438
caenorhabditis_elegans	rpl-25.2	WBGENE00004439

Protein

Protein identifiers

Large ribosomal subunit protein uL23 — P62750 (reviewed: P62750)

Alternative names: 60S ribosomal protein L23a

All UniProt accessions (6): A8MUS3, H7BY10, K7EJV9, K7EMA7, K7ERT8, P62750

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. Binds a specific region on the 26S rRNA. May promote p53/TP53 degradation possibly through the stimulation of MDM2-mediated TP53 polyubiquitination.

Subunit / interactions. Component of the large ribosomal subunit. Interacts with LYAR and GNL2. Interacts with MDM2; this interaction may promote MDM2-mediated p53/TP53 polyubiquitination. Directly interacts (via BIB domain) with IPO5, IPO7, KPNB1 and TNPO1; these interactions are involved in RPL23A nuclear import for the assembly of ribosomal subunits. Interacts with IPO8.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. N-terminus is methylated by METTL11A/NTM1. Citrullinated by PADI4.

Domain organisation. The N-terminal beta-like import receptor binding (BIB) domain mediates interaction with IPO5, IPO7, KPNB1 and TNPO1.

Induction. May be down-regulated by GNL2 (at protein level).

Similarity. Belongs to the universal ribosomal protein uL23 family.

RefSeq proteins (1): NP_000975* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001014	Ribosomal_uL23_CS	Conserved_site
IPR005633	Ribosomal_uL23_N	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR012678	Ribosomal_uL23/eL15/eS24_sf	Homologous_superfamily
IPR013025	Ribosomal_uL23-like	Family
IPR019985	Ribosomal_uL23	Family

Pfam: PF00276, PF03939

UniProt features (16 total): modified residue 5, sequence conflict 3, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

198 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
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
9P8B	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62750-F1	89.68	0.73

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 (6): 70, 14, 2, 41, 43, 45

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: 261 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, CREL_01, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_151, GNF2_TPT1, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, AACYNNNNTTCCS_UNKNOWN, GOBP_MALE_GAMETE_GENERATION, chr17q11, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, TCF4_Q5, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION, ATF1_Q6

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

GO Molecular Function (6): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), rRNA binding (GO:0019843), cadherin binding (GO:0045296), TORC2 complex binding (GO:1904841), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), extracellular exosome (GO:0070062), ribosome (GO:0005840), ribosomal subunit (GO:0044391), 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
ribosome	3
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
nucleic acid binding	1
structural molecule activity	1
RNA binding	1
cell adhesion molecule binding	1
protein-containing complex binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
extracellular vesicle	1
ribonucleoprotein complex	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

356 interactions, top by confidence:

A	B	Type	Score
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
JADE1	KAT7	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HERC3	RPL23A	psi-mi:“MI:0915”(physical association)	0.660
RPL23A	HERC3	psi-mi:“MI:0915”(physical association)	0.660
HERC3	RPL23A	psi-mi:“MI:0407”(direct interaction)	0.660
HERC3	RPL23A	psi-mi:“MI:0403”(colocalization)	0.660
HERC3	RPL23A	psi-mi:“MI:0220”(ubiquitination reaction)	0.660
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
SF3B1	RPL23A	psi-mi:“MI:0915”(physical association)	0.560
DDX10	RPL23A	psi-mi:“MI:0915”(physical association)	0.560
NOM1	RPLP0	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
PA2G4	RPL35	psi-mi:“MI:0915”(physical association)	0.500
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
RPL23A	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
AHNAK	RPL23A	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (910): RPL23A (Affinity Capture-MS), RPL23A (Affinity Capture-MS), RPL23A (Affinity Capture-MS), RPL23A (Affinity Capture-MS), RPL23A (Affinity Capture-MS), RPL23A (Affinity Capture-MS), RPL23A (Affinity Capture-MS), MRPL15 (Co-fractionation), MRPL16 (Co-fractionation), MRPS10 (Co-fractionation), MRPS7 (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL13A (Co-fractionation), RPL17 (Co-fractionation)

ESM2 similar proteins: A0A1D8PN83, A0A1D8PPS1, A3DJH4, B0B9K4, B0BB83, B1AIM2, B1AIM5, B1VAM4, B2UUV8, B5Z8J2, B5ZB42, B6JN36, B8I7Y1, G1SE76, O22644, O52334, O74391, O84098, P04456, P08792, P0A0X4, P0A0X5, P0CX47, P0CX48, P0DJ57, P41165, P48045, P48162, P51997, P62750, P62751, P62752, Q07761, Q10330, Q1CS69, Q20647, Q24JY1, Q252V5, Q3KMS4, Q54BQ3

Diamond homologs: A0A1D8PPS1, A0LIJ2, A3DNA6, A4FVY0, A5F547, A6UV66, A6VHD4, A7MWI5, A8G1E6, A8GYX8, A8LM50, A8MB73, A9A9B6, B0RZU2, B0TM10, B1KMY1, B1YGV2, B2TIH7, B2V7L1, B4U746, B5FG11, B6EPS7, B6YSL5, B7VLF5, B8CND5, C3LRQ6, C3PKQ4, C5A284, C5CC60, C6A161, G1SE76, O22644, O26112, O28356, O74095, O74391, P04456, P08792, P0ADZ0, P0ADZ1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL23A	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 215 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
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	21	16.6×	1e-17
SRP-dependent cotranslational protein targeting to membrane	23	15.5×	2e-18
Eukaryotic Translation Termination	19	15.3×	1e-15
Peptide chain elongation	18	15.3×	5e-15
Viral mRNA Translation	18	15.3×	5e-15
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	18	15.2×	6e-15
Selenocysteine synthesis	18	14.5×	1e-14
Eukaryotic Translation Initiation	7	14.5×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	21	20.5×	6e-19
stress granule assembly	6	19.0×	1e-04
positive regulation of transcription by RNA polymerase I	5	17.1×	1e-03
ribosomal large subunit biogenesis	6	14.0×	7e-04
negative regulation of innate immune response	5	13.4×	2e-03
rRNA processing	18	13.4×	5e-13
regulation of translational initiation	5	12.3×	3e-03
ribosomal small subunit biogenesis	10	12.0×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

530 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28720028:A:T	donor_gain	1.0000
17:28720702:CCCA:C	acceptor_loss	1.0000
17:28720705:A:AG	acceptor_gain	1.0000
17:28720706:G:GA	acceptor_gain	1.0000
17:28720706:GC:G	acceptor_gain	1.0000
17:28720706:GCT:G	acceptor_gain	1.0000
17:28720706:GCTC:G	acceptor_gain	1.0000
17:28720706:GCTCC:G	acceptor_gain	1.0000
17:28720867:G:GT	donor_gain	1.0000
17:28720887:ACAA:A	donor_gain	1.0000
17:28720889:AA:A	donor_gain	1.0000
17:28720889:AAGT:A	donor_loss	1.0000
17:28720891:G:GG	donor_gain	1.0000
17:28720891:GT:G	donor_loss	1.0000
17:28720892:T:A	donor_loss	1.0000
17:28720895:G:GG	donor_gain	1.0000
17:28722719:CCA:C	acceptor_loss	1.0000
17:28722720:CAGGC:C	acceptor_loss	1.0000
17:28722721:A:AC	acceptor_loss	1.0000
17:28722721:A:AG	acceptor_gain	1.0000
17:28722722:G:GG	acceptor_gain	1.0000
17:28722722:G:GT	acceptor_loss	1.0000
17:28722895:ATTCG:A	donor_gain	1.0000
17:28722896:TTCG:T	donor_gain	1.0000
17:28722897:TCG:T	donor_gain	1.0000
17:28722900:G:GG	donor_gain	1.0000
17:28722901:T:A	donor_loss	1.0000
17:28723566:CCTA:C	acceptor_loss	1.0000
17:28723567:CTA:C	acceptor_loss	1.0000
17:28723569:A:AG	acceptor_gain	1.0000

AlphaMissense

1013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28720817:T:C	F46L	1.000
17:28720819:C:A	F46L	1.000
17:28720819:C:G	F46L	1.000
17:28722752:C:A	P80Q	1.000
17:28722755:T:C	L81P	1.000
17:28722761:C:T	T83I	1.000
17:28722764:A:T	E84V	1.000
17:28722769:G:C	A86P	1.000
17:28722770:C:A	A86D	1.000
17:28722773:T:A	M87K	1.000
17:28722777:G:C	K88N	1.000
17:28722777:G:T	K88N	1.000
17:28722782:T:A	I90K	1.000
17:28722784:G:A	E91K	1.000
17:28722785:A:T	E91V	1.000
17:28722786:A:C	E91D	1.000
17:28722786:A:T	E91D	1.000
17:28722787:G:C	D92H	1.000
17:28722788:A:T	D92V	1.000
17:28722800:T:A	L96H	1.000
17:28722800:T:C	L96P	1.000
17:28722805:T:C	F98L	1.000
17:28722806:T:C	F98S	1.000
17:28722807:C:A	F98L	1.000
17:28722807:C:G	F98L	1.000
17:28722824:C:A	A104D	1.000
17:28722847:G:C	A112P	1.000
17:28722860:T:C	L116P	1.000
17:28722884:T:A	V124D	1.000
17:28722893:T:C	L127P	1.000

dbSNP variants (sampled 300 via entrez): RS1000340537 (17:28723984 C>A,G), RS1000673498 (17:28722930 G>C), RS1001178674 (17:28721773 CTCTT>C), RS1001666210 (17:28724805 A>G), RS1001859064 (17:28721564 T>A), RS1002162539 (17:28718946 G>C), RS1002499492 (17:28719714 AGTGAGCCGAGATCGCGCC>A), RS1002511645 (17:28718579 T>G), RS1002678307 (17:28720617 C>A,T), RS1002828875 (17:28721114 G>T), RS1003818876 (17:28722561 C>G), RS1004059044 (17:28718958 G>A), RS1006042735 (17:28721599 C>T), RS1006401451 (17:28720199 G>T), RS1007548977 (17:28722089 C>CA)

Disease associations

OMIM: gene MIM:602326 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006614_25	Total cholesterol levels	1.000000e-09
GCST90000025_576	Appendicular lean mass	8.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067559 (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

50 potent at pChembl≥5 of 54 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.87	Kd	13.66	nM	CHEMBL5653589
7.87	ED50	13.66	nM	CHEMBL5653589
6.98	Kd	104.9	nM	CHEMBL3752910
6.98	ED50	104.9	nM	CHEMBL3752910
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

48 with measured affinity, of 209 total; 28 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	2149254: Binding affinity to human RPL23A incubated for 45 mins by Kinobead based pull down assay	kd	0.0137	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149254: Binding affinity to human RPL23A incubated for 45 mins by Kinobead based pull down assay	kd	0.1049	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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases activity, increases expression	5
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression	3
bisphenol A	decreases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment, decreases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
artenimol	affects binding	1
epigallocatechin gallate	decreases expression	1
4-hydroxy-equilenin	increases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects localization, increases expression, affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects expression, affects response to substance	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.