RPL22

Summary

RPL22 (ribosomal protein L22, HGNC:10315) is a protein-coding gene on chromosome 1p36.31, encoding Large ribosomal subunit protein eL22 (P35268). Component of the large ribosomal subunit. It is a selective cancer dependency (DepMap: 24.3% 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 cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L22E family of ribosomal proteins. Its initiating methionine residue is post-translationally removed. The protein can bind specifically to Epstein-Barr virus-encoded RNAs (EBERs) 1 and 2. The mouse protein has been shown to be capable of binding to heparin. Transcript variants utilizing alternative polyA signals exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. It was previously thought that this gene mapped to 3q26 and that it was fused to the acute myeloid leukemia 1 (AML1) gene located at 21q22 in some therapy-related myelodysplastic syndrome patients with 3;21 translocations; however, these fusions actually involve a ribosomal protein L22 pseudogene located at 3q26, and this gene actually maps to 1p36.3-p36.2.

Source: NCBI Gene 6146 — RefSeq curated summary.

At a glance

• GWAS associations: 48
• Clinical variants (ClinVar): 14 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 24.3% of screened cell lines
• MANE Select transcript: NM_000983

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10315
Approved symbol	RPL22
Name	ribosomal protein L22
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Aliases	EAP, L22, eL22
Ensembl gene	ENSG00000116251
Ensembl biotype	protein_coding
OMIM	180474
Entrez	6146

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000234875, ENST00000462296, ENST00000465335, ENST00000465387, ENST00000471204, ENST00000480661, ENST00000497965, ENST00000929466, ENST00000929467, ENST00000929468, ENST00000929469, ENST00000929470

RefSeq mRNA: 1 — MANE Select: NM_000983 NM_000983

CCDS: CCDS58

Canonical transcript exons

ENST00000234875 — 4 exons

Exon	Start	End
ENSE00001064718	6199562	6199595
ENSE00001263346	6185020	6186816
ENSE00003594009	6197652	6197756
ENSE00003839072	6192930	6193054

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 476.9980 / max 4752.9875, expressed in 1828 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9989	472.7347	1828
9999	1.5240	624
9988	1.1659	661
9991	0.6575	188
9990	0.3984	216
9998	0.3086	110
9992	0.0783	43
9995	0.0567	31
10000	0.0474	15
9993	0.0177	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.79	gold quality
ganglionic eminence	UBERON:0004023	99.74	gold quality
cortical plate	UBERON:0005343	99.74	gold quality
left ovary	UBERON:0002119	99.67	gold quality
monocyte	CL:0000576	99.63	gold quality
ventricular zone	UBERON:0003053	99.63	gold quality
leukocyte	CL:0000738	99.61	gold quality
mononuclear cell	CL:0000842	99.61	gold quality
right ovary	UBERON:0002118	99.61	gold quality
endocervix	UBERON:0000458	99.57	gold quality
body of uterus	UBERON:0009853	99.57	gold quality
skin of abdomen	UBERON:0001416	99.56	gold quality
ovary	UBERON:0000992	99.55	gold quality
granulocyte	CL:0000094	99.54	gold quality
mucosa of stomach	UBERON:0001199	99.53	gold quality
skin of leg	UBERON:0001511	99.53	gold quality
body of pancreas	UBERON:0001150	99.52	gold quality
ectocervix	UBERON:0012249	99.52	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.49	gold quality
right lung	UBERON:0002167	99.48	gold quality
popliteal artery	UBERON:0002250	99.48	gold quality
tibial artery	UBERON:0007610	99.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.48	gold quality
left uterine tube	UBERON:0001303	99.47	gold quality
islet of Langerhans	UBERON:0000006	99.46	gold quality
peritoneum	UBERON:0002358	99.46	gold quality
omental fat pad	UBERON:0010414	99.46	gold quality
lower esophagus	UBERON:0013473	99.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.46	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	3063.12
E-CURD-88	yes	2877.05
E-CURD-122	yes	111.07
E-CURD-46	yes	46.13
E-CURD-112	yes	33.17
E-MTAB-10042	yes	15.61
E-HCAD-9	yes	10.72
E-GEOD-135922	yes	10.38
E-MTAB-9801	yes	6.52
E-HCAD-32	no	2965.52
E-CURD-95	no	2880.50
E-HCAD-8	no	2869.32
E-CURD-77	no	2762.74
E-MTAB-8911	no	2321.31
E-HCAD-4	no	118.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KMT2A, MYC

miRNA regulators (miRDB)

73 targeting RPL22, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-518A-5P	99.70	69.01	2209

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• The EBER in situ hybridization showed negative results despite racial or geographical factors might influence the peculiar susceptibility of individuals of Asian ancestry to Epstein-Barr virus-associated lymphoepithelioma-like carcinoma. (PMID:15812220)
• Multiple domains of EBER 1 recruit ribosomal protein L22. (PMID:16556938)
• The EBER-ISH as an independent prognostic factor of NPC regardless of histopathology. (PMID:16564389)
• Growth-promoting properties of Epstein-Barr virus EBER-1 RNA correlate with ribosomal protein L22 binding (PMID:19640998)
• Rpl22 inactivation promotes neoplastic transformation by inducing expression of Lin28B (PMID:22976955)
• RPL22 is frequently mutated in MSI-high endometrioid endometrial cancers. The A8 mutation identified was not reported in the whole exome sequences analyzed by the TCGA. (PMID:23127973)
• Down-regulation of RPL22 might be involved in the carcinogenesis of NSCLC. (PMID:23797773)
• Study revealved that RPL22 binds CK2alpha in lung cancer cells. (PMID:24840952)
• considering the high mutation frequency found, our data point toward an important role for RPL22 in microsatellite instability carcinogenesis (PMID:25196364)
• Intratumoral Heterogeneity of RPL22 Frameshift Mutation in Colorectal Cancers. (PMID:29860580)
• RPL22/eL22 can interact with and inhibit CDK4-Cyclin D1 to decrease RB phosphorylation. (PMID:30874462)
• Post-transcriptional regulation of C-C motif chemokine ligand 2 expression by ribosomal protein L22 during LPS-mediated inflammation. (PMID:32383535)
• RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior. (PMID:34220863)
• L22 ribosomal protein is involved in dynamin-related protein 1-mediated gastric carcinoma progression. (PMID:35230214)
• CRISPR screening uncovers nucleolar RPL22 as a heterochromatin destabilizer and senescence driver. (PMID:39258545)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl22	ENSDARG00000070437
mus_musculus	Rpl22	ENSMUSG00000028936
rattus_norvegicus	Rpl22-ps2	ENSRNOG00000028747

Paralogs (1): RPL22L1 (ENSG00000163584)

Protein

Protein identifiers

Large ribosomal subunit protein eL22 — P35268 (reviewed: P35268)

Alternative names: 60S ribosomal protein L22, EBER-associated protein, Epstein-Barr virus small RNA-associated protein, Heparin-binding protein HBp15

All UniProt accessions (6): K7EJT5, K7ELC4, K7EMH1, K7EP65, K7ERI7, P35268

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.

Miscellaneous. Binds to Epstein-Barr virus small RNAs and to heparin.

Similarity. Belongs to the eukaryotic ribosomal protein eL22 family.

RefSeq proteins (1): NP_000974* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002671	Ribosomal_eL22	Family
IPR038526	Ribosomal_eL22_sf	Homologous_superfamily

Pfam: PF01776

UniProt features (5 total): modified residue 3, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

139 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
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
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
7XNY	ELECTRON MICROSCOPY	2.5
8JDJ	ELECTRON MICROSCOPY	2.5
9RUC	ELECTRON MICROSCOPY	2.5
8FL3	ELECTRON MICROSCOPY	2.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35268-F1	84.48	0.69

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 (3): 62, 66, 69

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: 296 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, RNGTGGGC_UNKNOWN, MORF_SNRP70, MORF_UBE2I, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, CTATGCA_MIR153, USF_C, GOBP_TRANSLATION, MORF_CCNI, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GNF2_FBL, HIF1_Q3

GO Biological Process (4): cytoplasmic translation (GO:0002181), translation (GO:0006412), alpha-beta T cell differentiation (GO:0046632), translation at presynapse (GO:0140236)

GO Molecular Function (5): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), heparin binding (GO:0008201), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), extracellular exosome (GO:0070062), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), ribonucleoprotein complex (GO:1990904), ribosome (GO:0005840), synapse (GO:0045202)

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	3
ribosome	2
synapse	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
T cell differentiation	1
alpha-beta T cell activation	1
presynapse	1
translation at synapse	1
nucleic acid binding	1
structural molecule activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
extracellular vesicle	1
protein-containing complex	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

2774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL22	RPS8	P09058	852
RPL22	RPS14	P06366	840
RPL22	RPL4	P36578	838
RPL22	RPS19	P39019	808
RPL22	MECOM	Q03112	801
RPL22	RPL38	P23411	787
RPL22	RPS9	P46781	776
RPL22	RPL5	P46777	772
RPL22	RPS6	P08227	767
RPL22	RPL19	P14118	748
RPL22	RPL26	P61254	745
RPL22	RPS3	P23396	744
RPL22	RPL21	P46778	741
RPL22	RPL14	P50914	733
RPL22	RPS16	P17008	732

IntAct

294 interactions, top by confidence:

A	B	Type	Score
RPL22	SDCBP2	psi-mi:“MI:0915”(physical association)	0.700
RPL22	SDCBP	psi-mi:“MI:0915”(physical association)	0.700
SDCBP2	RPL22	psi-mi:“MI:0915”(physical association)	0.700
SDCBP	RPL22	psi-mi:“MI:0915”(physical association)	0.700
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPL22	FGF11	psi-mi:“MI:0915”(physical association)	0.560
RPL22	BEND7	psi-mi:“MI:0915”(physical association)	0.560
RPL22	THAP1	psi-mi:“MI:0915”(physical association)	0.560
RPL22	STAC3	psi-mi:“MI:0915”(physical association)	0.560
RPL22	CT45A1	psi-mi:“MI:0915”(physical association)	0.560
RPL22	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
SURF6	RPL22	psi-mi:“MI:0915”(physical association)	0.560
RPL22	RPL22	psi-mi:“MI:0915”(physical association)	0.560
RPL22	AP2M1	psi-mi:“MI:0915”(physical association)	0.560
RPL22	H2BC15	psi-mi:“MI:0915”(physical association)	0.560
RPL22	ZCCHC10	psi-mi:“MI:0915”(physical association)	0.560
RPL22	HTT	psi-mi:“MI:0915”(physical association)	0.560
RPL22	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
ABCE1	EIF3H	psi-mi:“MI:0914”(association)	0.530
RPL13	RPLP1	psi-mi:“MI:0914”(association)	0.530
RPL22	BAG4	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (593): RPL22 (Affinity Capture-MS), RPL22 (Affinity Capture-MS), RPL22 (Affinity Capture-MS), RPL22 (Affinity Capture-MS), RPL22 (Affinity Capture-MS), RPL22 (Affinity Capture-MS), RPL22 (Affinity Capture-MS), RPL22 (Affinity Capture-MS), HNRNPU (Co-fractionation), LUC7L2 (Co-fractionation), RPL10 (Co-fractionation), RPL10A (Co-fractionation), RPL11 (Co-fractionation), RPL12 (Co-fractionation), RPL13 (Co-fractionation)

ESM2 similar proteins: A2YDY2, A4FUH0, G1TG89, G1TSG1, P35268, P42794, P42798, P47198, P48597, P50886, P50894, P52865, P62084, P62244, P62245, P62246, P62495, P62496, P62497, P62498, P67984, P67985, P86048, Q0DK10, Q0VCX5, Q28IL6, Q32L19, Q4R4D3, Q4R5I3, Q5I0R6, Q5NVP9, Q5R4C7, Q5R938, Q5U2Q7, Q6AYU1, Q6P5R6, Q6Q420, Q76I82, Q8BWY3, Q8CJ19

Diamond homologs: A0A1D8PM41, A4FUH0, G1TSG1, P05749, P13732, P35268, P47198, P50886, P50887, P52819, P52865, P56628, P67984, P67985, Q09668, Q23BV5, Q28IL6, Q4R5I3, Q54GK6, Q54JE3, Q5I0R6, Q6P5R6, Q90YU6, Q98TF8, Q9D7S7, Q9FE58, Q9M9W1, Q9SRX7, Q8SS49

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RPL22	down-regulates	RPL22L1
RPL22	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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
Formation of the ternary complex, and subsequently, the 43S complex	9	15.5×	3e-07
Ribosomal scanning and start codon recognition	10	15.2×	8e-08
Translation initiation complex formation	9	13.7×	8e-07
GTP hydrolysis and joining of the 60S ribosomal subunit	17	13.6×	4e-12
Formation of a pool of free 40S subunits	15	13.4×	7e-11
Nuclear events stimulated by ALK signaling in cancer	5	13.1×	1e-03
L13a-mediated translational silencing of Ceruloplasmin expression	16	12.9×	3e-11
SARS-CoV-1 modulates host translation machinery	5	12.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	6	42.7×	9e-07
stress granule assembly	6	22.9×	3e-05
translational initiation	10	22.7×	1e-08
regulation of translational initiation	6	17.8×	1e-04
cytoplasmic translation	14	16.4×	2e-10
mRNA stabilization	7	16.2×	3e-05
mitophagy	7	14.1×	8e-05
intrinsic apoptotic signaling pathway	6	13.6×	6e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — HCC.

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1855 predictions. Top by Δscore:

Variant	Effect	Δscore
1:6186813:ATACC:A	acceptor_loss	1.0000
1:6186814:TACC:T	acceptor_loss	1.0000
1:6186815:ACCTG:A	acceptor_loss	1.0000
1:6186816:CCTG:C	acceptor_loss	1.0000
1:6186817:C:T	acceptor_loss	1.0000
1:6186818:T:A	acceptor_loss	1.0000
1:6192919:C:A	donor_gain	1.0000
1:6192927:TACCT:T	donor_loss	1.0000
1:6192928:A:T	donor_loss	1.0000
1:6193053:TCCTG:T	acceptor_loss	1.0000
1:6193056:T:A	acceptor_loss	1.0000
1:6197650:A:AC	donor_gain	1.0000
1:6197651:C:CC	donor_gain	1.0000
1:6197651:CA:C	donor_gain	1.0000
1:6197651:CAAAA:C	donor_gain	1.0000
1:6197755:TTCT:T	acceptor_loss	1.0000
1:6197757:C:CC	acceptor_gain	1.0000
1:6197757:C:CG	acceptor_loss	1.0000
1:6197758:T:A	acceptor_loss	1.0000
1:6206299:GCGG:G	donor_gain	1.0000
1:6206301:GG:G	donor_gain	1.0000
1:6206302:GG:G	donor_gain	1.0000
1:6206303:G:A	donor_loss	1.0000
1:6206303:G:GG	donor_gain	1.0000
1:6206304:T:A	donor_loss	1.0000
1:6206723:GCCA:G	donor_gain	1.0000
1:6206727:G:GG	donor_gain	1.0000
1:6208880:GGAC:G	acceptor_gain	1.0000
1:6209018:G:GT	donor_gain	1.0000
1:6209021:GTGCA:G	donor_gain	1.0000

AlphaMissense

854 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6186709:A:G	I117T	1.000
1:6186714:G:C	F115L	1.000
1:6186714:G:T	F115L	1.000
1:6186715:A:C	F115C	1.000
1:6186715:A:G	F115S	1.000
1:6186716:A:C	F115V	1.000
1:6186716:A:G	F115L	1.000
1:6186716:A:T	F115I	1.000
1:6186718:T:C	Y114C	1.000
1:6186719:A:C	Y114D	1.000
1:6186719:A:G	Y114H	1.000
1:6186721:C:G	R113P	1.000
1:6186724:A:G	L112S	1.000
1:6186748:G:T	A104D	1.000
1:6186751:A:T	V103D	1.000
1:6186754:A:T	V102E	1.000
1:6186758:G:T	R101S	1.000
1:6186759:C:A	L100F	1.000
1:6186759:C:G	L100F	1.000
1:6186760:A:C	L100W	1.000
1:6186760:A:G	L100S	1.000
1:6186762:C:A	W99C	1.000
1:6186762:C:G	W99C	1.000
1:6186763:C:A	W99L	1.000
1:6186763:C:G	W99S	1.000
1:6186764:A:G	W99R	1.000
1:6186764:A:T	W99R	1.000
1:6186766:T:A	D98V	1.000
1:6186766:T:C	D98G	1.000
1:6186766:T:G	D98A	1.000

dbSNP variants (sampled 300 via entrez): RS1000253798 (1:6199598 G>A), RS1000306208 (1:6199813 G>A), RS1000315948 (1:6188337 A>G), RS1000346771 (1:6188678 G>A), RS1000460573 (1:6194793 T>C,G), RS1000589433 (1:6201270 T>G), RS1000640349 (1:6201563 C>A,G), RS1000767145 (1:6195725 T>G), RS1001199406 (1:6195861 G>A,C), RS1001881066 (1:6186377 C>T), RS1002249299 (1:6197996 C>A), RS1002326418 (1:6190768 C>G,T), RS1002334933 (1:6186032 T>A), RS1002543766 (1:6189135 C>T), RS1002596919 (1:6198347 G>A,C,T)

Disease associations

OMIM: gene MIM:180474 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

48 associations (top):

Study	Trait	p-value
GCST010346_11	TPE interval (resting)	2.000000e-11
GCST010346_52	TPE interval (resting)	5.000000e-18
GCST010796_1076	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-24
GCST010796_1077	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-25
GCST010796_1078	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-25
GCST010796_1079	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-25
GCST010796_1080	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-26
GCST010796_1081	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-27
GCST010796_1082	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-26
GCST010796_1083	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-26
GCST010796_1084	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-25
GCST010796_1085	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-24
GCST010796_1086	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-25
GCST010796_1088	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-25
GCST010796_1089	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-23
GCST010796_1090	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-22
GCST010796_1091	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-21
GCST010796_1092	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-20
GCST010796_1093	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-19
GCST010796_1094	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-18
GCST010796_1095	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-16
GCST010796_1096	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-15
GCST010796_1097	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-13
GCST010796_1098	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_1099	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-12
GCST010796_1100	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010796_1101	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1102	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_1103	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-27
GCST010796_1211	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-25

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004644	TPE interval measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066913 (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 53 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.12	Kd	7.584	nM	CHEMBL5653589
8.12	ED50	7.584	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 215 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	2149252: Binding affinity to human RPL22 incubated for 45 mins by Kinobead based pull down assay	kd	0.0076	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	5
sodium arsenite	decreases expression	2
chloropicrin	affects expression, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
uranyl acetate	affects expression	1
arsenite	affects binding, increases reaction	1
beryllium sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
azoxystrobin	increases expression	1
pyrimidifen	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1
Decitabine	affects methylation	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	decreases methylation	1

ChEMBL screening assays

96 unique, capped per target: 96 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 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3G8	Abcam HEK293T RPL22 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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