RPL34

Summary

RPL34 (ribosomal protein L34, HGNC:10340) is a protein-coding gene on chromosome 4q25, encoding Large ribosomal subunit protein eL34 (P49207). 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 L34E family of ribosomal proteins. It is located in the cytoplasm. This gene originally was thought to be located at 17q21, but it has been mapped to 4q. Overexpression of this gene has been observed in some cancer cells. Alternative splicing results in multiple transcript variants, all encoding the same isoform. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6164 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 18 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_001319236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10340
Approved symbol	RPL34
Name	ribosomal protein L34
Location	4q25
Locus type	gene with protein product
Status	Approved
Aliases	L34, eL34
Ensembl gene	ENSG00000109475
Ensembl biotype	protein_coding
OMIM	616862
Entrez	6164

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 2 retained_intron

ENST00000394665, ENST00000394667, ENST00000394668, ENST00000502534, ENST00000503574, ENST00000504231, ENST00000506397, ENST00000853717, ENST00000853718, ENST00000853719, ENST00000853720, ENST00000853721, ENST00000926072, ENST00000926073, ENST00000926074, ENST00000926075, ENST00000926076, ENST00000926077, ENST00000926078, ENST00000926079, ENST00000926080, ENST00000926081, ENST00000926082, ENST00000926083, ENST00000968424

RefSeq mRNA: 6 — MANE Select: NM_001319236 NM_000995, NM_001319232, NM_001319234, NM_001319235, NM_001319236, NM_033625

CCDS: CCDS3680

Canonical transcript exons

ENST00000394667 — 5 exons

Exon	Start	End
ENSE00001081294	108622515	108622618
ENSE00001081295	108622105	108622204
ENSE00001195942	108621951	108622024
ENSE00001627468	108620576	108620600
ENSE00003911059	108625128	108625370

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.4506 / max 894.6417, expressed in 1821 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49216	49.2488	1816
49217	21.1092	1787
49218	15.9926	1685
49214	2.8163	1096
49215	1.2838	799

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.97	gold quality
caput epididymis	UBERON:0004358	99.97	gold quality
corpus epididymis	UBERON:0004359	99.97	gold quality
mammary duct	UBERON:0001765	99.96	gold quality
cartilage tissue	UBERON:0002418	99.96	gold quality
calcaneal tendon	UBERON:0003701	99.96	gold quality
cauda epididymis	UBERON:0004360	99.96	gold quality
cranial nerve II	UBERON:0000941	99.95	gold quality
mucosa of urinary bladder	UBERON:0001259	99.95	gold quality
epithelium of mammary gland	UBERON:0003244	99.95	gold quality
skin of hip	UBERON:0001554	99.93	gold quality
superficial temporal artery	UBERON:0001614	99.93	gold quality
ganglionic eminence	UBERON:0004023	99.93	gold quality
upper leg skin	UBERON:0004262	99.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.93	gold quality
cortical plate	UBERON:0005343	99.93	gold quality
colonic mucosa	UBERON:0000317	99.92	gold quality
embryo	UBERON:0000922	99.92	gold quality
left ovary	UBERON:0002119	99.92	gold quality
layer of synovial tissue	UBERON:0007616	99.92	gold quality
lower lobe of lung	UBERON:0008949	99.92	gold quality
pituitary gland	UBERON:0000007	99.91	gold quality
endocervix	UBERON:0000458	99.91	gold quality
right ovary	UBERON:0002118	99.91	gold quality
adenohypophysis	UBERON:0002196	99.91	gold quality
trabecular bone tissue	UBERON:0002483	99.91	gold quality
body of uterus	UBERON:0009853	99.91	gold quality
tendon	UBERON:0000043	99.90	gold quality
mammalian vulva	UBERON:0000997	99.90	gold quality

Single-cell (SCXA)

Detected in 59 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	11277.75
E-MTAB-9221	yes	9018.65
E-CURD-98	yes	8111.80
E-GEOD-135922	yes	7642.52
E-CURD-122	yes	7553.30
E-MTAB-9067	yes	4892.59
E-MTAB-4850	yes	1135.45
E-MTAB-6678	yes	34.70
E-CURD-112	yes	30.63
E-MTAB-10042	yes	16.44
E-MTAB-9543	yes	10.94
E-HCAD-35	yes	10.19
E-MTAB-9801	yes	6.32
E-GEOD-137537	yes	5.99
E-MTAB-5061	yes	4.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting RPL34, 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-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-4708-5P	97.77	67.82	831

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 9)

• RPL34 plays a critical role in cell proliferation, cell cycle distribution and apoptosis of human malignant gastric cells. (PMID:26323242)
• over-expressed RPL34 may promote malignant proliferation of NSCLC cells, thus playing an important role in development and progress of NSCLC (PMID:26526135)
• this study shows that ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells (PMID:27845896)
• RPL34 plays an important role in the proliferation of osteosarcoma cells. (PMID:27883047)
• RPL34 functions as an oncogene that modulates the proliferation and metastasis of esophageal cancer cells in part through the inactivation of the PI3K/Akt signaling pathway (PMID:28109079)
• The RPL34 gene was highly expressed in OSCC, while silencing RPL34 could block cell proliferation and metastasis, but promote cell apoptosis, suggesting the RPL34 gene to be a new promising clinical target for OSCC therapy. (PMID:28697409)
• The present study combines an individual-based phenotypic profiling with a transdiagnostic approach and shows that several ribosomal genes including RPL34 is involved in stress vulnerability across nonclinical and clinical conditions. (PMID:30103068)
• Findings indicated that knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK/STAT3 signaling pathway. (PMID:30216512)
• RPL34-AS1-induced RPL34 inhibits cervical cancer cell tumorigenesis via the MDM2-P53 pathway. (PMID:33675124)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl34	ENSDARG00000029500
mus_musculus	Rpl34	ENSMUSG00000062006
rattus_norvegicus	Rpl34l1	ENSRNOG00000038045

Protein

Protein identifiers

Large ribosomal subunit protein eL34 — P49207 (reviewed: P49207)

Alternative names: 60S ribosomal protein L34

All UniProt accessions (1): P49207

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. Cytosol. Endoplasmic reticulum.

Similarity. Belongs to the eukaryotic ribosomal protein eL34 family.

RefSeq proteins (6): NP_000986, NP_001306161, NP_001306163, NP_001306164, NP_001306165, NP_296374 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008195	Ribosomal_eL34	Family
IPR018065	Ribosomal_eL34_CS	Conserved_site
IPR038562	Ribosomal_eL34_C_sf	Homologous_superfamily

Pfam: PF01199

UniProt features (9 total): modified residue 3, sequence conflict 3, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

185 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
9QLO	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49207-F1	90.86	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 12, 36, 43, 108

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: 256 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CYTOPLASMIC_TRANSLATION, chr4q25, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_151, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GCM_NPM1, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, CHX10_01, COUP_01, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

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

GO Molecular Function (4): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (10): nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), synapse (GO:0045202), extracellular exosome (GO:0070062), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribosome	2
intracellular membraneless organelle	2
cellular anatomical structure	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
cell adhesion molecule binding	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
extracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

2701 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL34	RPL6	Q02878	746
RPL34	RPL35	P42766	726
RPL34	RPL8	P25120	720
RPL34	RPL31	P12947	709
RPL34	RPL29	P47914	704
RPL34	RPL11	P25121	683
RPL34	RPL4	P36578	678
RPL34	RPL26	P61254	677
RPL34	RPL28	P46779	669
RPL34	RPL36	Q9Y3U8	669
RPL34	RPL9	P32969	649
RPL34	RPS24	P16632	647
RPL34	RPL7A	P11518	644
RPL34	RPL21	P46778	627
RPL34	RPS21	P35265	623

IntAct

160 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
RPL34	LRRK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
RPL34	NPM1	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
RPL34	RPL27	psi-mi:“MI:0915”(physical association)	0.400
RPL34	RPL30	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
RPL34	DAPK3	psi-mi:“MI:0915”(physical association)	0.370
KBTBD7	DKFZp686H10254	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (430): RPL34 (Affinity Capture-RNA), RPL34 (Affinity Capture-RNA), RPL34 (Affinity Capture-MS), RPL34 (Affinity Capture-MS), RPL34 (Affinity Capture-MS), EIF6 (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation), RPL13A (Co-fractionation), RPL14 (Co-fractionation), RPL15 (Co-fractionation), RPL21 (Co-fractionation), RPL23 (Co-fractionation), RPL23A (Co-fractionation), RPL24 (Co-fractionation)

ESM2 similar proteins: A0A381, A4GGF5, A5PK63, A9LYE6, G1SZ47, G1TG89, G1TU13, G1TXG5, O63057, P04644, P07135, P08636, P08708, P49207, P62244, P62245, P62246, P62266, P62267, P62268, P62298, P63273, P63274, P63275, P63276, P82129, Q09WV9, Q29223, Q3BAH4, Q3T199, Q589A4, Q67IL8, Q6EM56, Q6EM77, Q6EM90, Q6EV23, Q6KGX9, Q6QAP7, Q6SA96, Q76I82

Diamond homologs: A0A1D8PDZ1, A1RXV1, A2BME5, A6USC2, A6UW33, G1TXG5, O42846, O74006, P0DJ23, P11250, P40525, P40590, P41098, P45842, P49207, P87262, Q1WBV0, Q29223, Q42351, Q54LV8, Q7ZWJ7, Q8SSA2, Q8U2L3, Q90YT5, Q9D1R9, Q9FE65, Q9LJW6, Q9NB34, Q9URT8, Q9UZJ7, A1RRJ4, A3DND2, A3MV68, A5UL62, B1YAJ9, B6YSP0, C3MQ85, C3MVX7, C3N5V3, C3NEG9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL34	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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	17	14.2×	1e-12
Eukaryotic Translation Termination	13	13.0×	3e-09
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	13	12.8×	3e-09
Peptide chain elongation	12	12.7×	1e-08
Viral mRNA Translation	12	12.7×	1e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	12	12.6×	1e-08
Selenocysteine synthesis	12	12.0×	2e-08
Response of EIF2AK4 (GCN2) to amino acid deficiency	13	12.0×	6e-09

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	5	25.5×	3e-04
ribosomal large subunit biogenesis	7	20.7×	1e-05
cytoplasmic translation	15	18.5×	3e-12
rRNA processing	13	12.3×	2e-08
translation	15	10.3×	1e-08
ribosomal small subunit biogenesis	6	9.1×	5e-03
negative regulation of translation	6	7.8×	1e-02
mRNA splicing, via spliceosome	9	5.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

361 predictions. Top by Δscore:

Variant	Effect	Δscore
4:108622020:AGGCT:A	donor_gain	1.0000
4:108622021:GGCT:G	donor_gain	1.0000
4:108622021:GGCTG:G	donor_gain	1.0000
4:108622022:GCT:G	donor_gain	1.0000
4:108622022:GCTG:G	donor_gain	1.0000
4:108622023:CT:C	donor_gain	1.0000
4:108622025:G:GG	donor_gain	1.0000
4:108622100:TCTA:T	acceptor_loss	1.0000
4:108622101:CTA:C	acceptor_loss	1.0000
4:108622103:A:AG	acceptor_gain	1.0000
4:108622104:G:GG	acceptor_gain	1.0000
4:108622200:GAGGG:G	donor_gain	1.0000
4:108622201:AGGG:A	donor_gain	1.0000
4:108622202:GGG:G	donor_gain	1.0000
4:108622202:GGGG:G	donor_gain	1.0000
4:108622203:GG:G	donor_gain	1.0000
4:108622203:GGG:G	donor_gain	1.0000
4:108622204:GG:G	donor_gain	1.0000
4:108622205:G:GG	donor_gain	1.0000
4:108622205:GTAAG:G	donor_loss	1.0000
4:108622206:T:G	donor_loss	1.0000
4:108622510:TGCA:T	acceptor_loss	1.0000
4:108622511:GCAG:G	acceptor_loss	1.0000
4:108622512:CAGGT:C	acceptor_loss	1.0000
4:108622514:GGTTC:G	acceptor_gain	1.0000
4:108622614:GACAG:G	donor_gain	1.0000
4:108622615:ACAGG:A	donor_loss	1.0000
4:108622618:GGT:G	donor_loss	1.0000
4:108622619:G:GC	donor_loss	1.0000
4:108622619:G:GG	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS10000321 (4:108629038 G>A,T), RS1000267587 (4:108623126 G>A), RS1000396080 (4:108627931 T>G), RS1000514685 (4:108622155 G>A), RS1000638637 (4:108627698 C>T), RS1000641148 (4:108623329 T>C,G), RS1000745782 (4:108627044 C>T), RS1001095431 (4:108621617 CTCTT>C), RS1001176454 (4:108626871 A>C,T), RS1002220051 (4:108620546 G>A), RS1002448903 (4:108625872 C>A,G), RS1002557184 (4:108619134 G>C), RS10026091 (4:108630424 A>G,T), RS1002808934 (4:108629978 G>C), RS1002821605 (4:108626090 A>G)

Disease associations

OMIM: gene MIM:616862 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002647_141	Height	6.000000e-15
GCST006988_52	Blond vs. brown/black hair color	3.000000e-20
GCST010241_319	Apolipoprotein A1 levels	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066885 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.07	Kd	85.59	nM	CHEMBL5653589
7.07	ED50	85.59	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 207 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	2149263: Binding affinity to human RPL34 incubated for 45 mins by Kinobead based pull down assay	kd	0.0856	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects expression, affects cotreatment, increases methylation	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
Particulate Matter	affects cotreatment, decreases expression, increases abundance	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	increases expression, affects cotreatment	1
chromium hexavalent ion	increases expression	1
chloropicrin	increases expression	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic 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.