RPL13A

Summary

RPL13A (ribosomal protein L13a, HGNC:10304) is a protein-coding gene on chromosome 19q13.33, encoding Large ribosomal subunit protein uL13 (P40429). Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. 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 member of the L13P family of ribosomal proteins that is a component of the 60S subunit. The encoded protein also plays a role in the repression of inflammatory genes as a component of the IFN-gamma-activated inhibitor of translation (GAIT) complex. This gene is co-transcribed with the small nucleolar RNA genes U32, U33, U34, and U35, which are located in the second, fourth, fifth, and sixth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 23521 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 39 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_012423

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10304
Approved symbol	RPL13A
Name	ribosomal protein L13a
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	L13A, uL13
Ensembl gene	ENSG00000142541
Ensembl biotype	protein_coding
OMIM	619225
Entrez	23521

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 17 protein_coding, 13 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000391857, ENST00000467825, ENST00000468655, ENST00000472481, ENST00000474171, ENST00000476268, ENST00000476300, ENST00000477613, ENST00000479992, ENST00000484279, ENST00000486930, ENST00000488946, ENST00000621674, ENST00000624069, ENST00000676477, ENST00000676556, ENST00000677048, ENST00000678146, ENST00000678187, ENST00000678510, ENST00000678713, ENST00000679106, ENST00000857998, ENST00000857999, ENST00000858000, ENST00000915794, ENST00000915795, ENST00000915796, ENST00000915797, ENST00000915798, ENST00000915799, ENST00000915800, ENST00000961389, ENST00000961390

RefSeq mRNA: 2 — MANE Select: NM_012423 NM_001270491, NM_012423

CCDS: CCDS12768, CCDS74421

Canonical transcript exons

ENST00000391857 — 8 exons

Exon	Start	End
ENSE00001921398	49491729	49492308
ENSE00003469199	49489850	49489922
ENSE00003484997	49491040	49491099
ENSE00003515321	49490232	49490297
ENSE00003573818	49487608	49487644
ENSE00003611819	49490779	49490864
ENSE00003634584	49490475	49490576
ENSE00003692236	49491425	49491547

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 474.0198 / max 4412.6882, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176995	472.7675	1828
176998	1.2524	686

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.95	gold quality
right ovary	UBERON:0002118	99.95	gold quality
left ovary	UBERON:0002119	99.95	gold quality
endocervix	UBERON:0000458	99.94	gold quality
ovary	UBERON:0000992	99.94	gold quality
skin of abdomen	UBERON:0001416	99.93	gold quality
zone of skin	UBERON:0000014	99.92	gold quality
vagina	UBERON:0000996	99.92	gold quality
right lobe of thyroid gland	UBERON:0001119	99.92	gold quality
left lobe of thyroid gland	UBERON:0001120	99.92	gold quality
left uterine tube	UBERON:0001303	99.92	gold quality
skin of leg	UBERON:0001511	99.92	gold quality
thyroid gland	UBERON:0002046	99.92	gold quality
prostate gland	UBERON:0002367	99.92	gold quality
ganglionic eminence	UBERON:0004023	99.92	gold quality
cortical plate	UBERON:0005343	99.92	gold quality
body of uterus	UBERON:0009853	99.92	gold quality
ectocervix	UBERON:0012249	99.92	gold quality
left adrenal gland cortex	UBERON:0035825	99.92	gold quality
pituitary gland	UBERON:0000007	99.91	gold quality
lymph node	UBERON:0000029	99.91	gold quality
body of stomach	UBERON:0001161	99.91	gold quality
right adrenal gland	UBERON:0001233	99.91	gold quality
left adrenal gland	UBERON:0001234	99.91	gold quality
adenohypophysis	UBERON:0002196	99.91	gold quality
ventricular zone	UBERON:0003053	99.91	gold quality
thoracic mammary gland	UBERON:0005200	99.91	gold quality
omental fat pad	UBERON:0010414	99.91	gold quality
metanephros cortex	UBERON:0010533	99.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.91	gold quality

Single-cell (SCXA)

Detected in 45 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	10285.46
E-HCAD-9	yes	9365.65
E-MTAB-11268	yes	3703.43
E-HCAD-35	yes	2294.57
E-CURD-122	yes	102.66
E-CURD-88	yes	57.03
E-MTAB-9221	yes	54.87
E-MTAB-6678	yes	48.09
E-CURD-112	yes	33.37
E-MTAB-10042	yes	10.81
E-MTAB-9801	yes	6.36
E-GEOD-137537	yes	6.14
E-MTAB-6653	no	14671.36
E-CURD-46	no	13633.56
E-MTAB-6308	no	13036.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

26 targeting RPL13A, 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-6876-5P	100.00	67.68	2126
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-4281	92.91	63.60	271

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 10)

• A translational silencing mechanism involving regulated release of RPL13a and subsequent binding to its target mRNA was elucidated. (PMID:14567916)
• L13a may have evolved from an essential ribosomal protein in lower eukaryotes to having a role as a dispensable extra-ribosomal function in higher eukaryotes. (PMID:17921318)
• Data show that EF1alpha, RPL13a and YWHAZ are suitable genes for the RT-qPCR analysis and comparison of several sources of human MSC during in vitro characterization and differentiation as well as in an ex vivo animal model of global cerebral ischemia. (PMID:20716364)
• The study found two ribosomal proteins, RPS7 and RPL13A that interact with the HMG (high-mobility group) box domain of SRY. (PMID:21114473)
• Ribosomal protein l13a is a reference gene for human bone marrow-derived mesenchymal stromal cells during expansion, adipo-, chondro-, and osteogenesis (PMID:22533734)
• GAPDH functions as a chaperone, shielding newly released RPL13a from proteasomal degradation. (PMID:22771119)
• This work identified the arginine residue at position 68 of L13A as being essential for L13A binding to rRNA and incorporation into ribosomes. (PMID:23689135)
• The expression of RPL13A and EEF1A1 was not affected by differentiation, thus being these genes the most stable candidates as reference genes for RT-PCR. (PMID:27304673)
• show through cellular immunofluorescence experiments that nuclear but not nucleolar localization of L13a is resistant to extensive amino acid alterations, suggesting that multiple complex nuclear import signals are present within this protein (PMID:31308261)
• Moonlight human ribosomal protein L13a downregulation is associated with p53 and HER2/neu expression in breast cancer. (PMID:34907725)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl13a	ENSDARG00000044093
mus_musculus	Rpl13a	ENSMUSG00000074129
drosophila_melanogaster	RpL13A	FBGN0037351
caenorhabditis_elegans		WBGENE00004428

Paralogs (1): MRPL13 (ENSG00000172172)

Protein

Protein identifiers

Large ribosomal subunit protein uL13 — P40429 (reviewed: P40429)

Alternative names: 23 kDa highly basic protein, 60S ribosomal protein L13a

All UniProt accessions (9): P40429, A0A096LPE0, A0A384ME37, A0A7I2V2L9, A0A7I2V376, A0A7I2V5L3, M0QYS1, M0QZU1, Q8J015

UniProt curated annotations — full annotation on UniProt →

Function. Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the ribosome and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3’-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. In the GAIT complex interacts with m7G cap-bound eIF4G at or near the eIF3-binding site and blocks the recruitment of the 43S ribosomal complex. Involved in methylation of rRNA.

Subunit / interactions. Component of the 60S ribosome. Component of the GAIT complex. Interacts with EIF4G1.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylation at Ser-77 upon interferon-gamma treatment in monocytes involves a DAPK1-DAPK3 kinase cascade and is causing release from the ribosome, association with the GAIT complex and subsequent involvement in transcript-selective translation inhibition. Citrullinated by PADI4.

Similarity. Belongs to the universal ribosomal protein uL13 family.

RefSeq proteins (2): NP_001257420, NP_036555* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005755	Ribosomal_uL13_euk_arc	Family
IPR005822	Ribosomal_uL13	Family
IPR023563	Ribosomal_uL13_CS	Conserved_site
IPR036899	Ribosomal_uL13_sf	Homologous_superfamily

Pfam: PF00572

UniProt features (8 total): modified residue 5, initiator methionine 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

194 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-P40429-F1	95.86	0.97

Functional residue map

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

Post-translational modifications (5): 2, 59, 77, 140, 191

Mutagenesis-validated functional residues (1):

Position	Phenotype
77	loss of interferon-gamma induced phosphorylation.

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: 334 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, HORIUCHI_WTAP_TARGETS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, MODULE_151, GNF2_TPT1, GCM_NPM1, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_LUNG_MORPHOGENESIS, HSIAO_HOUSEKEEPING_GENES, GOBP_TRANSLATIONAL_INITIATION, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2

GO Biological Process (11): cytoplasmic translation (GO:0002181), translation (GO:0006412), negative regulation of translation (GO:0017148), response to lipopolysaccharide (GO:0032496), positive regulation of natural killer cell proliferation (GO:0032819), homeostatic process (GO:0042592), macrophage chemotaxis (GO:0048246), lung morphogenesis (GO:0060425), cellular response to type II interferon (GO:0071346), negative regulation of formation of translation preinitiation complex (GO:1901194), regulation of translation (GO:0006417)

GO Molecular Function (3): RNA binding (GO:0003723), mRNA binding (GO:0003729), structural constituent of ribosome (GO:0003735)

GO Cellular Component (13): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), large ribosomal subunit (GO:0015934), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), synapse (GO:0045202), GAIT complex (GO:0097452), 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
translation	3
cellular anatomical structure	3
ribosome	2
intracellular membraneless organelle	2
protein-containing complex	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
natural killer cell proliferation	1
positive regulation of natural killer cell activation	1
regulation of natural killer cell proliferation	1
positive regulation of lymphocyte proliferation	1
biological_process	1
leukocyte chemotaxis	1
macrophage migration	1
animal organ morphogenesis	1
lung development	1
response to type II interferon	1
cellular response to cytokine stimulus	1
formation of translation preinitiation complex	1
negative regulation of protein-containing complex assembly	1
regulation of formation of translation preinitiation complex	1
negative regulation of cytoplasmic translational initiation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
RNA binding	1
structural molecule activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

5953 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL13A	EPRS1	P07814	997
RPL13A	GAPDH	P00354	997
RPL13A	SYNCRIP	O60506	996
RPL13A	RPS16	P17008	854
RPL13A	SDHA	P31040	813
RPL13A	PARS2	Q7L3T8	801
RPL13A	EIF4G1	Q04637	769
RPL13A	RPS20	P17075	749
RPL13A	YWHAZ	P29213	749
RPL13A	CP	P00450	747
RPL13A	B2M	P01884	735
RPL13A	RPL32	P02433	729
RPL13A	POTEF	A5A3E0	720
RPL13A	RPS18	P25232	706
RPL13A	ACTB	P02570	700

IntAct

282 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPL13A	E6	psi-mi:“MI:0915”(physical association)	0.550
RPL13A	RPL30	psi-mi:“MI:0915”(physical association)	0.550
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
AURKAIP1	NRDC	psi-mi:“MI:0914”(association)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
ADGRF5	RPL13A	psi-mi:“MI:0915”(physical association)	0.400
TET3	RPL13A	psi-mi:“MI:0915”(physical association)	0.400
TOMM70	RPL13A	psi-mi:“MI:0915”(physical association)	0.400
RPL13A	RPL35A	psi-mi:“MI:0915”(physical association)	0.400
EPRS1	RPL13A	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	MCRIP1	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	PABPC1	psi-mi:“MI:0915”(physical association)	0.400
NS	RPL13A	psi-mi:“MI:0915”(physical association)	0.370
RPL13A	ALDH2	psi-mi:“MI:0915”(physical association)	0.370
RPL13A	CRP	psi-mi:“MI:0915”(physical association)	0.370
RPL13A	CYP2E1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (801): RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), RPL13A (Affinity Capture-MS), EIF6 (Co-fractionation), FBL (Co-fractionation), PABPC1 (Co-fractionation), PABPC4 (Co-fractionation)

ESM2 similar proteins: A0A1D8PDL6, A0BD73, A0CEY2, A5GFQ0, G1SV32, G1TVS8, O01802, O22431, O60143, O65729, O96647, P05426, P05737, P0DJ13, P11874, P14148, P17937, P18124, P19253, P25457, P32100, P35427, P40429, P60039, P60040, P93847, Q12213, Q1HR62, Q3SZ90, Q4GXG7, Q4PM04, Q4R506, Q4R8Z2, Q58DT1, Q5R9R4, Q5RA38, Q5RAH8, Q5ZJ56, Q6BTA4, Q6C603

Diamond homologs: A1ATL1, A1RSE1, A3MZW6, A4SDB9, A5IMD1, A6Q6N9, A7MJB9, A9WH96, B0BUF9, B0K5S7, B0KCN4, B0U6Z6, B1LBJ2, B1YC32, B2IAE8, B3H129, B5EFM9, B8F3F6, B8G6P5, B9JD18, B9JVC5, B9LJG2, C0ZIL3, C4XNQ2, C6E4S8, G1TVS8, O26146, O29137, O42848, O42991, O43004, O49885, O59300, P0DJ15, P19253, P26784, P26785, P29198, P35427, P39473

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DAPK3	up-regulates	RPL13A	phosphorylation
RPL13A	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 216 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)	18	14.1×	1e-13
SRP-dependent cotranslational protein targeting to membrane	21	14.0×	8e-16
Eukaryotic Translation Termination	17	13.6×	5e-13
Peptide chain elongation	16	13.5×	2e-12
Viral mRNA Translation	16	13.5×	2e-12
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	16	13.4×	2e-12
Selenocysteine synthesis	16	12.8×	4e-12
Response of EIF2AK4 (GCN2) to amino acid deficiency	17	12.6×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	19	18.8×	3e-16
stress granule assembly	5	16.1×	2e-03
ribosomal large subunit biogenesis	6	14.2×	7e-04
negative regulation of translation	13	13.6×	5e-09
translation	22	12.1×	5e-15
mRNA stabilization	6	11.8×	2e-03
rRNA processing	14	10.6×	2e-08
ribosomal small subunit biogenesis	8	9.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

901 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49487642:CAGG:C	donor_loss	1.0000
19:49487645:GTAT:G	donor_loss	1.0000
19:49487646:T:A	donor_loss	1.0000
19:49488604:G:GT	donor_gain	1.0000
19:49489844:CCACA:C	acceptor_loss	1.0000
19:49489845:CACA:C	acceptor_loss	1.0000
19:49489847:CA:C	acceptor_loss	1.0000
19:49489848:A:AG	acceptor_gain	1.0000
19:49489848:AGGTC:A	acceptor_loss	1.0000
19:49489849:G:GA	acceptor_gain	1.0000
19:49489849:GGT:G	acceptor_gain	1.0000
19:49489849:GGTC:G	acceptor_gain	1.0000
19:49489849:GGTCC:G	acceptor_gain	1.0000
19:49489918:GCTGG:G	donor_gain	1.0000
19:49489921:GG:G	donor_gain	1.0000
19:49489922:GG:G	donor_gain	1.0000
19:49489923:G:GG	donor_gain	1.0000
19:49490228:CTAG:C	acceptor_loss	1.0000
19:49490229:TA:T	acceptor_loss	1.0000
19:49490230:A:AC	acceptor_loss	1.0000
19:49490230:A:AG	acceptor_gain	1.0000
19:49490231:G:GT	acceptor_gain	1.0000
19:49490293:CAAGT:C	donor_gain	1.0000
19:49490296:GT:G	donor_gain	1.0000
19:49490298:G:GG	donor_gain	1.0000
19:49490303:T:G	donor_gain	1.0000
19:49490469:CCCTA:C	acceptor_loss	1.0000
19:49490473:A:AG	acceptor_gain	1.0000
19:49490473:AGT:A	acceptor_gain	1.0000
19:49490474:G:GC	acceptor_gain	1.0000

AlphaMissense

1297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49489883:G:A	G17S	1.000
19:49489883:G:C	G17R	1.000
19:49489883:G:T	G17C	1.000
19:49489884:G:A	G17D	1.000
19:49489884:G:T	G17V	1.000
19:49490256:G:A	C38Y	1.000
19:49490257:T:G	C38W	1.000
19:49490276:G:C	G45R	1.000
19:49490277:G:A	G45D	1.000
19:49490277:G:T	G45V	1.000
19:49490289:G:C	R49T	1.000
19:49490289:G:T	R49I	1.000
19:49490489:T:C	F57L	1.000
19:49490491:C:A	F57L	1.000
19:49490491:C:G	F57L	1.000
19:49490525:G:C	G69R	1.000
19:49490526:G:A	G69D	1.000
19:49490534:C:G	H72D	1.000
19:49490547:C:A	P76H	1.000
19:49490576:G:C	G86R	1.000
19:49490779:G:A	G86D	1.000
19:49490782:T:C	M87T	1.000
19:49490783:G:A	M87I	1.000
19:49490783:G:C	M87I	1.000
19:49490783:G:T	M87I	1.000
19:49490805:G:C	G95R	1.000
19:49490806:G:A	G95D	1.000
19:49490806:G:T	G95V	1.000
19:49491065:C:A	A123D	1.000
19:49491447:C:A	A142D	1.000

dbSNP variants (sampled 300 via entrez): RS1001030771 (19:49486790 A>C), RS1001127408 (19:49489093 G>A), RS1001145061 (19:49486433 C>T), RS1001344901 (19:49485628 C>T), RS1001661897 (19:49489293 C>CAAG), RS1001944060 (19:49489496 T>C), RS1002496676 (19:49488606 A>C), RS1002609619 (19:49488450 G>A), RS1002781632 (19:49492402 T>A,C), RS1002890787 (19:49487882 G>A,C), RS1002972031 (19:49492531 C>T), RS1003247669 (19:49488093 A>G), RS1003498231 (19:49487857 G>A,C), RS1003611805 (19:49487745 A>G), RS1004616857 (19:49486877 T>C)

Disease associations

OMIM: gene MIM:619225 | 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
GCST000583_10	Hematological and biochemical traits	3.000000e-08
GCST90002393_667	Monocyte count	6.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066905 (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
7.15	Kd	70.63	nM	CHEMBL5653589
7.15	ED50	70.63	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	2149244: Binding affinity to human RPL13A incubated for 45 mins by Kinobead based pull down assay	kd	0.0706	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, affects cotreatment	4
Estradiol	increases expression, increases reaction, decreases expression, decreases reaction	3
Particulate Matter	increases expression, increases abundance, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
sodium arsenite	decreases expression	2
bisphenol S	decreases expression, increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Rotenone	increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
TAK-243	increases sumoylation	1
deoxynivalenol	increases expression	1
beta-lapachone	decreases expression, increases expression	1
2,6-dichloro-4-nitrophenol	increases expression	1
3,3’-diindolylmethane	increases expression, increases reaction	1
ochratoxin A	increases expression	1
benzo(e)pyrene	decreases methylation	1
evodiamine	decreases expression	1
arsenic disulfide	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
azoxystrobin	increases expression	1
CD 437	decreases expression	1
chloropicrin	affects expression	1
monomethylarsonous 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
candoxin	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, 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.