RPS2

Summary

RPS2 (ribosomal protein S2, HGNC:10404) is a protein-coding gene on chromosome 16p13.3, encoding Small ribosomal subunit protein uS5 (P15880). Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. It is a common-essential gene (DepMap: required in 99.7% 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 40S subunit. The protein belongs to the S5P family of ribosomal proteins. It is located in the cytoplasm. This gene shares sequence similarity with mouse LLRep3. It is co-transcribed with the small nucleolar RNA gene U64, which is located in its third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6187 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 39 total
• Regional missense constraint (gnomAD): 2 of 7 regions constrained (≈14% of expected missense variation)
• GTEx eGene: eQTL in 40 tissues, sQTL in 4 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.49 (moderately constrained)
• MANE Select transcript: NM_002952
• Interaction hub: 4,486 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10404
Approved symbol	RPS2
Name	ribosomal protein S2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	LLREP3, S2, uS5
Ensembl gene	ENSG00000140988
Ensembl biotype	protein_coding
OMIM	603624
Entrez	6187

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 35 protein_coding, 8 retained_intron, 7 nonsense_mediated_decay

MANE Select: ENST00000343262

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 5, TSL 3: 4, TSL 5: 3

ENST00000343262, ENST00000526522, ENST00000526586, ENST00000526908, ENST00000527109, ENST00000527302, ENST00000527826, ENST00000527871, ENST00000529806, ENST00000530225, ENST00000531065, ENST00000532746, ENST00000533161, ENST00000533186, ENST00000533872, ENST00000534461, ENST00000563194, ENST00000872227, ENST00000872228, ENST00000872229, ENST00000872230, ENST00000872231, ENST00000872232, ENST00000872233, ENST00000872234, ENST00000929923, ENST00000929924, ENST00000929925, ENST00000929926, ENST00000968780, ENST00000968781, ENST00000968782, ENST00001007246, ENST00001007247, ENST00001007248, ENST00001007249, ENST00001022278, ENST00001022280, ENST00001022282, ENST00001022285, ENST00001022287, ENST00001083694, ENST00001083702, ENST00001083703, ENST00001090863, ENST00001090864, ENST00001090865, ENST00001090866, ENST00001090867, ENST00001137232

RefSeq mRNA: 1 — MANE Select: NM_002952 NM_002952

CCDS: CCDS10452

Canonical transcript exons

ENST00000343262 — 7 exons

Exon	Start	End
ENSE00001411617	1964807	1964826
ENSE00002615156	1962058	1962270
ENSE00003384926	1964449	1964628
ENSE00003476243	1964276	1964365
ENSE00003535003	1963149	1963256
ENSE00003596226	1962736	1962909
ENSE00003624369	1962497	1962656

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.0759 / max 475.6973, expressed in 1819 samples.

Highest expression (Bgee): stromal cell of endometrium, uterine tube, ovary, body of pancreas, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RPS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 40 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 44 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	4.5e-40	-0.27	16:1960137:G:A
Testis	eqtl	3.6e-34	-0.34	16:1965551:TGGC:T
Esophagus Mucosa	eqtl	9.9e-33	-0.34	16:1964282:A:G
Skin Sun Exposed Lower leg	eqtl	1.7e-31	-0.23	16:1964282:A:G
Nerve Tibial	eqtl	1.0e-27	+0.26	16:1964124:C:T
Cells EBV-transformed lymphocytes	eqtl	4.0e-23	-0.49	16:1960137:G:A
Whole Blood	eqtl	5.2e-22	-0.14	16:1964282:A:G
Skin Not Sun Exposed Suprapubic	eqtl	4.1e-18	-0.21	16:1964282:A:G
Adipose Subcutaneous	eqtl	9.6e-18	-0.20	16:1965551:TGGC:T
Muscle Skeletal	eqtl	1.2e-13	-0.27	16:1973321:C:T
Pancreas	eqtl	1.8e-12	-0.27	16:1964282:A:G
Adipose Visceral Omentum	eqtl	1.2e-10	-0.15	16:1964282:A:G
Thyroid	eqtl	1.5e-09	-0.16	16:1964282:A:G
Spleen	eqtl	2.0e-09	-0.20	16:1964282:A:G
Breast Mammary Tissue	eqtl	4.9e-09	+0.20	16:1964777:A:G
Artery Tibial	eqtl	7.7e-08	-0.14	16:1973371:A:C
Esophagus Muscularis	eqtl	2.5e-07	-0.17	16:1973371:A:C
Artery Aorta	eqtl	4.5e-07	-0.18	16:1964282:A:G
Heart Atrial Appendage	eqtl	1.6e-06	-0.23	16:1955617:G:A
Lung	eqtl	2.8e-06	+0.16	16:1964124:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
155890	72.9337	1819
155889	0.1422	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.89	gold quality
right uterine tube	UBERON:0001302	99.88	gold quality
ovary	UBERON:0000992	99.86	gold quality
body of pancreas	UBERON:0001150	99.86	gold quality
right ovary	UBERON:0002118	99.86	gold quality
left ovary	UBERON:0002119	99.86	gold quality
ventricular zone	UBERON:0003053	99.86	gold quality
cortical plate	UBERON:0005343	99.86	gold quality
granulocyte	CL:0000094	99.85	gold quality
ganglionic eminence	UBERON:0004023	99.85	gold quality
mucosa of transverse colon	UBERON:0004991	99.85	gold quality
zone of skin	UBERON:0000014	99.84	gold quality
skin of abdomen	UBERON:0001416	99.84	gold quality
skin of leg	UBERON:0001511	99.84	gold quality
lymph node	UBERON:0000029	99.83	gold quality
spleen	UBERON:0002106	99.83	gold quality
esophagus mucosa	UBERON:0002469	99.83	gold quality
fallopian tube	UBERON:0003889	99.83	gold quality
endocervix	UBERON:0000458	99.82	gold quality
adenohypophysis	UBERON:0002196	99.82	gold quality
thoracic mammary gland	UBERON:0005200	99.82	gold quality
lower esophagus mucosa	UBERON:0035834	99.82	gold quality
leukocyte	CL:0000738	99.81	gold quality
pituitary gland	UBERON:0000007	99.81	gold quality
left uterine tube	UBERON:0001303	99.81	gold quality
placenta	UBERON:0001987	99.81	gold quality
prostate gland	UBERON:0002367	99.81	gold quality
ectocervix	UBERON:0012249	99.81	gold quality
monocyte	CL:0000576	99.80	gold quality
vagina	UBERON:0000996	99.80	gold quality
esophagus	UBERON:0001043	99.80	gold quality
transverse colon	UBERON:0001157	99.80	gold quality
body of stomach	UBERON:0001161	99.80	gold quality
cortex of kidney	UBERON:0001225	99.80	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.80	gold quality
body of uterus	UBERON:0009853	99.80	gold quality
metanephros cortex	UBERON:0010533	99.80	gold quality
left adrenal gland cortex	UBERON:0035825	99.80	gold quality
uterine cervix	UBERON:0000002	99.79	gold quality
adipose tissue	UBERON:0001013	99.79	gold quality
fundus of stomach	UBERON:0001160	99.79	gold quality
bone marrow	UBERON:0002371	99.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.79	gold quality
upper lobe of left lung	UBERON:0008952	99.79	gold quality
stomach	UBERON:0000945	99.78	gold quality
right lobe of thyroid gland	UBERON:0001119	99.78	gold quality
vermiform appendix	UBERON:0001154	99.78	gold quality
right adrenal gland	UBERON:0001233	99.78	gold quality
left adrenal gland	UBERON:0001234	99.78	gold quality
urinary bladder	UBERON:0001255	99.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.78	gold quality
omental fat pad	UBERON:0010414	99.78	gold quality
colon	UBERON:0001155	99.77	gold quality
minor salivary gland	UBERON:0001830	99.77	gold quality
apex of heart	UBERON:0002098	99.77	gold quality
small intestine	UBERON:0002108	99.77	gold quality
bone marrow cell	CL:0002092	99.76	gold quality
blood	UBERON:0000178	99.76	gold quality
saliva-secreting gland	UBERON:0001044	99.76	gold quality
myometrium	UBERON:0001296	99.76	gold quality
lower esophagus	UBERON:0013473	99.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.76	gold quality
intestine	UBERON:0000160	99.75	gold quality
left lobe of thyroid gland	UBERON:0001120	99.75	gold quality
gastrocnemius	UBERON:0001388	99.75	gold quality
thyroid gland	UBERON:0002046	99.75	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.75	gold quality
tibial nerve	UBERON:0001323	99.74	gold quality
left coronary artery	UBERON:0001626	99.74	gold quality
adrenal gland	UBERON:0002369	99.74	gold quality
right adrenal gland cortex	UBERON:0035827	99.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.74	gold quality
mucosa of stomach	UBERON:0001199	99.73	gold quality
lung	UBERON:0002048	99.73	gold quality
skeletal muscle tissue	UBERON:0001134	99.72	gold quality
muscle of leg	UBERON:0001383	99.72	gold quality
gall bladder	UBERON:0002110	99.72	gold quality
tonsil	UBERON:0002372	99.72	gold quality
right coronary artery	UBERON:0001625	99.71	gold quality
right lung	UBERON:0002167	99.71	gold quality
pancreas	UBERON:0001264	99.70	gold quality
muscle tissue	UBERON:0002385	99.70	gold quality
colonic epithelium	UBERON:0000397	99.69	gold quality
duodenum	UBERON:0002114	99.69	gold quality
right atrium auricular region	UBERON:0006631	99.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.66	gold quality
descending thoracic aorta	UBERON:0002345	99.66	gold quality
left testis	UBERON:0004533	99.66	gold quality
right testis	UBERON:0004534	99.66	gold quality
heart	UBERON:0000948	99.65	gold quality
smooth muscle tissue	UBERON:0001135	99.65	gold quality
ascending aorta	UBERON:0001496	99.65	gold quality
thoracic aorta	UBERON:0001515	99.65	gold quality
putamen	UBERON:0001874	99.64	gold quality
popliteal artery	UBERON:0002250	99.64	gold quality
tibial artery	UBERON:0007610	99.64	gold quality
adult mammalian kidney	UBERON:0000082	99.63	gold quality
caudate nucleus	UBERON:0001873	99.63	gold quality
heart left ventricle	UBERON:0002084	99.63	gold quality

Single-cell (SCXA)

Detected in 55 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	16529.57
E-MTAB-6308	yes	16268.04
E-CURD-112	yes	9857.34
E-CURD-46	yes	8373.87
E-MTAB-8205	yes	8048.06
E-MTAB-9221	yes	7072.46
E-MTAB-11011	yes	4713.18
E-GEOD-137537	yes	4108.40
E-GEOD-130473	yes	2516.60
E-MTAB-8142	yes	179.08
E-CURD-122	yes	81.53
E-CURD-88	yes	57.62
E-HCAD-9	yes	32.33
E-GEOD-81547	yes	20.32
E-MTAB-7316	yes	17.84

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 72 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	2955.2	not detected
Bone marrow	tissue	2595.3	not detected
Pancreas	tissue	2261.5	low
Lymph node	tissue	1789.3	not detected
Vagina	tissue	1775.4	not detected
Skin 1	tissue	1769.5	not detected
Skeletal muscle	tissue	1571.7	low
Tonsil	tissue	1500.4	not detected
Thymus	tissue	1462.9
Tongue	tissue	1454.7
Breast	tissue	1434.5	not detected
Corpus callosum	tissue	1365.9
Esophagus	tissue	1356.9	not detected
Fallopian tube	tissue	1318.4	not detected
Urinary bladder	tissue	1223.5	medium
Salivary gland	tissue	1160.9	low
Colon	tissue	1042.5	medium
Appendix	tissue	1015.6	medium
Spleen	tissue	1005.2	not detected
Pituitary gland	tissue	969.2
Duodenum	tissue	898.7	high
Cervix	tissue	853.3	not detected
Stomach 1	tissue	844.7	high
Small intestine	tissue	822.9	medium
Basal ganglia	tissue	791.7	medium
Caudate putamen	tissue	791.7
Placenta	tissue	781.7	not detected
Amygdala	tissue	745.4
Heart muscle	tissue	735.9	medium
Rectum	tissue	715.2	medium
Ventral forebrain	tissue	711.4
Adipose tissue	tissue	682.1	low
Prostate	tissue	680.9	low
Septum	tissue	675.4
Cerebral cortex	tissue	674.1	low
Frontal cortex	tissue	674.1
Somatosensory cortex	tissue	656.0
Gallbladder	tissue	652.4	medium
Retrosplenial and cingulate cortex	tissue	651.9
Thyroid gland	tissue	651.2	not detected
Hippocampal formation	tissue	644.3
Occipital cortex	tissue	636.9
Seminal vesicle	tissue	599.7	low
Entorhinal cortex	tissue	597.0
Medulla oblongata	tissue	587.7
Epididymis	tissue	581.0	low
Adrenal gland	tissue	578.6	low
Smooth muscle	tissue	575.3	not detected
Endometrium 1	tissue	572.4	low
Spinal cord	tissue	547.7
Lung	tissue	518.9	not detected
Liver	tissue	492.4	not detected
Hypothalamus	tissue	473.8
Olfactory bulb	tissue	473.4
Thalamus	tissue	455.3
Putamen	tissue	453.8
Choroid plexus	tissue	440.8
Nucleus accumbens	tissue	433.0
Pons	tissue	424.9
Substantia nigra	tissue	424.7

Brain sub-regions (HPA Brain Atlas): detected in 186; highest nTPM — White matter (1365.9), Blood vessel (1196.5), Nucleus gracilis (587.7), Area postrema (563.8), Nucleus raphe pallidus (560.0).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 0.979, LOEUF 0.493, missense Z 2.75 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000343262 splits into 7 regions with different missense tolerance; 2 are missense-constrained (≈14% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
16:1,962,101–1,962,166	32 / 29.4	1.09	no
16:1,962,167–1,962,826	79 / 159.0	0.50	no
16:1,962,827–1,962,863	1 / 18.2	0.05	yes (p 5.4e-05)
16:1,962,864–1,962,899	15 / 18.4	0.81	no
16:1,962,900–1,963,220	5 / 37.6	0.13	yes (p 1.1e-07)
16:1,963,221–1,964,573	70 / 119.0	0.59	no
16:1,964,574–1,964,625	27 / 26.4	1.02	no
DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SW 620 (-3.558), FaDu (-3.463), NRH-LS3 (-3.283), RKO (-3.221), D458 (-3.186), JHOC-5 (-3.078), MV4-11 (-3.043), SNU-C5 (-3.022), LS513 (-2.984), CHP-212 (-2.95), HT-29 (-2.945), LS1034 (-2.934), MDST8 (-2.89), KMS-11 (-2.888), HSC-3 (-2.845).

Literature-anchored findings (GeneRIF, showing 14)

• two genes coding for ribosomal proteins (S2 and L10a) encoded tumor antigens recognized by HLA-A26-restricted CTLs (PMID:12694581)
• rpS2 is methylated by PRMT3 in vitro and is also methylated in cell lines. Deletion analysis of the rpS2 amino acid sequence identified a N-terminal Arg-Gly repeat as the methylation site. (PMID:15473865)
• the nuclear targeting domain shares no significant similarity to already characterized nuclear localization signals in ribosomal proteins or other nuclear proteins (PMID:16061210)
• These findings suggest that the nuclear form of FGF3 inhibits cell proliferation by interfering with ribosomal biogenesis. (PMID:16263090)
• These results suggest that in addition to its catalytic function, PRMT3 may control the level of rpS2 protein in cells by inhibiting ubiquitin-mediated proteolysis of rpS2. (PMID:18573314)
• RPS2 or other aberrantly over-expressed ribosomal proteins might promote cancer and be excellent therapeutic targets for treatment of the disease (PMID:19138403)
• PAD4 citrullinates the Arg-Gly repeat region of RPS2, which is also an established site for Arg methylation by protein arginine methyltransferase 3 (PRMT3). (PMID:21584310)
• Findings uncover the existence of an extra-ribosomal complex consisting of PDCD2L, RPS2, and PRMT3 and support a role for PDCD2L in the late maturation of 40S ribosomal subunits. (PMID:27697862)
• ZNF277 and PRMT3 compete for uS5 binding, because overexpression of PRMT3 inhibited the formation of the ZNF277-uS5 complex, whereas depletion of cellular ZNF277 resulted in increased levels of uS5-PRMT3. (PMID:30530495)
• The RPS2([r78-94]) peptide is further extended from its N- and C-termini until reaching two spatially vicinal residues 74 and 98 in the crystal structure of intact BMP2-receptor complex system, consequently resulting in a longer peptide RPS2([r74-98]), which is then cyclized in a head-to-tail manner to obtain its cyclic counterpart cycRPS2([r74-98]). (PMID:31894111)
• Ribosomal protein S2 interplays with MDM2 to induce p53. (PMID:31928715)
• PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2). (PMID:33245768)
• Silencing of long chain noncoding RNA paternally expressed gene (PEG10) inhibits the progression of neuroblastoma by regulating microRNA-449a (miR-449a)/ribosomal protein S2 (RPS2) axis. (PMID:35212607)
• DNA methylation-mediated epigenetic regulation of oncogenic RPS2 as a novel therapeutic target and biomarker in hepatocellular carcinoma. (PMID:38181486)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps2	ENSDARG00000077291
rattus_norvegicus	Rps2-ps17	ENSRNOG00000063807
drosophila_melanogaster	RpS2	FBGN0004867
caenorhabditis_elegans		WBGENE00004471

Paralogs (1): MRPS5 (ENSG00000144029)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:105110) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
weakness	1
decreased body weight	1
oxidative stress	1
decreased total body fat amount	1
decreased grip strength	1
increased circulating creatine kinase level	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Methanococcus vannielii SB	A6UQ64	100.0%	Diamond
Methanococcus vannielii	P14036	100.0%	Diamond
Mus musculus	P25444	100.0%	Diamond
Cricetulus griseus	P46791	100.0%	Diamond
Arabidopsis thaliana	Q8L8Y0	99.6%	Diamond
Bos taurus	O18789	99.5%	Diamond
Methanosarcina mazei Go1	Q8PV30	99.5%	Diamond
Methanosarcina acetivorans C2A	Q8TRS7	99.5%	Diamond
Methanococcus maripaludis C7	A6VH05	99.1%	Diamond
Methanococcus maripaludis C6	A9A9P4	99.1%	Diamond
Methanococcus maripaludis S2	Q6LXD3	98.7%	Diamond
Methanococcus maripaludis C5	A4FWA1	98.2%	Diamond
Ictalurus punctatus	Q90YS3	97.5%	Diamond
Oryctolagus cuniculus	G1SWM1	96.9%	Diamond
Saccharolobus islandicus Y.N.15.51	C3NH89	96.3%	Diamond
Saccharolobus solfataricus P2	Q9UX87	96.3%	Diamond
Pyrococcus horikoshii OT3	O59439	96.2%	Diamond
Pyrococcus abyssi GE5	Q9V1V5	96.2%	Diamond
Pyrococcus furiosus DSM 3638	Q8U017	94.9%	Diamond
Methanosarcina barkeri str. Fusaro	Q46GB5	94.2%	Diamond
Pyrobaculum islandicum DSM 4184	A1RU37	93.1%	Diamond
Urechis caupo	P49154	93.1%	Diamond
Pyrobaculum aerophilum str. IM2	Q8ZXN9	93.1%	Diamond
Pyrobaculum arsenaticum DSM 13514	A4WHQ8	92.6%	Diamond
Pyrobaculum calidifontis JCM 11548	A3MU88	92.1%	Diamond
Thermoplasma volcanium GSS1	Q97BV6	91.4%	Diamond
Thermoplasma acidophilum DSM 1728	Q9HIS7	91.4%	Diamond
Thermococcus kodakarensis KOD1	Q5JJG8	90.9%	Diamond
Methanococcus aeolicus Nankai-3	A6UWV8	85.8%	Diamond
Sulfurisphaera tokodaii str. 7	Q975K0	81.8%	Diamond
Sulfolobus acidocaldarius DSM 639	O05641	80.8%	Diamond
Methanobrevibacter smithii ATCC 35061	A5UL68	80.1%	Diamond
Methanothermobacter thermautotrophicus str. Delta H	O26131	80.1%	Diamond
Saccharomyces cerevisiae S288C	P25443	79.9%	Diamond
Methanosphaera stadtmanae DSM 3091	Q2NFX7	79.9%	Diamond
Haloquadratum walsbyi DSM 16790	Q18GG9	79.8%	Diamond
Natronomonas pharaonis DSM 2160	Q3IMW8	79.8%	Diamond
Haloarcula marismortui ATCC 43049	P26815	79.7%	Diamond
Halobacterium salinarum NRC-1	Q9HPB4	79.7%	Diamond
Methanoculleus marisnigri JR1	A3CT17	79.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02124	ncRNA	105371048
NDUFB10	protein-coding	4716
MSRB1	protein-coding	51734
SNORA10	snoRNA	574042
RPL3L	protein-coding	6123
HS3ST6	protein-coding	64711
RNF151	protein-coding	146310
SNORA64	snoRNA	26784
SNORA78	snoRNA	677844
SNHG9	ncRNA	735301
TBL3	protein-coding	10607
NOXO1	protein-coding	124056
GFER	protein-coding	2671

Protein

Protein identifiers

Small ribosomal subunit protein uS5 — P15880 (reviewed: P15880)

Alternative names: 40S ribosomal protein S2, 40S ribosomal protein S4, Protein LLRep3

All UniProt accessions (9): E9PM36, E9PMM9, E9PPT0, E9PQD7, P15880, H0YE27, H0YEN5, H3BNG3, I3L404

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. Plays a role in the assembly and function of the 40S ribosomal subunit. Mutations in this protein affects the control of translational fidelity. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.

Subunit / interactions. Component of the small ribosomal subunit. Interacts with zinc finger protein ZNF277 (via zinc-finger domains); the interaction is direct; the interaction is extra-ribosomal. Interaction with ZNF277 competes with the binding of RPS2 to protein arginine methyltransferase PRMT3. Interacts with PRMT3. Interacts with PDCD2; the interaction is direct, occurs cotranslationally, and serves to chaperone uS5 to assembly sites in the nucleus. Interacts with PDCD2L; for chaperone function of PDC2L. Interacts (when monoubiquitinated at Lys-54 and Lys-58) with RIOK3.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Post-translational modifications. Citrullinated by PADI4 in the Arg/Gly-rich region. Asymmetric arginine dimethylation by PRMT3 occurs at multiple sites in the Arg/Gly-rich region. Monoubiquitinated at Lys-54 and Lys-58 by RNF10 when a ribosome has stalled during translation, leading to its degradation by the proteasome. Monoubiquitination at Lys-54 and Lys-58 promotes interaction with RIOK3. Deubiquitinated at Lys-54 and Lys-58 by USP10, preventing degradation by the proteasome and promoting 40S ribosome subunit recycling following ribosome dissociation.

Similarity. Belongs to the universal ribosomal protein uS5 family.

RefSeq proteins (1): NP_002943* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000851	Ribosomal_uS5	Family
IPR005324	Ribosomal_uS5_C	Domain
IPR005711	Ribosomal_uS5_euk_arc	Family
IPR013810	Ribosomal_uS5_N	Domain
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR018192	Ribosomal_uS5_N_CS	Conserved_site
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily

Pfam: PF00333, PF03719

UniProt features (47 total): helix 14, strand 11, modified residue 7, cross-link 5, mutagenesis site 3, compositionally biased region 2, initiator methionine 1, chain 1, domain 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

showing 30 of 204 structures by resolution:

PDB	Title	Method	Resolution (Å)
8GLP	mRNA decoding in human is kinetically and structurally distinct from bacteria (Consensus …	ELECTRON MICROSCOPY	1.67
8QOI	Structure of the human 80S ribosome at 1.9 A resolution - the molecular role of chemical …	ELECTRON MICROSCOPY	1.9
9O3W	Human 80S ribosome bound to IDB-001 stalled on MYC nascent chain	ELECTRON MICROSCOPY	1.9
8YOO	Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline	ELECTRON MICROSCOPY	2
9C3H	Structure of the CNOT3-bound human 80S ribosome with tRNA-ARG in the P-site.	ELECTRON MICROSCOPY	2
7R4X	Cryo-EM reconstruction of the human 40S ribosomal subunit - Full map	ELECTRON MICROSCOPY	2.15
9I2D	NMT1-NAC bound human RNC with 10 amino acid ARF1-linker	ELECTRON MICROSCOPY	2.19
9PBE	In situ human 80S ribosome (composite map)	ELECTRON MICROSCOPY	2.19
8YOP	Cryo-EM structure of the human 80S ribosome with 4 um Tigecycline	ELECTRON MICROSCOPY	2.2
9O3V	Human 80S ribosome stalled on MYC nascent chain	ELECTRON MICROSCOPY	2.2
9O3Y	Human 80S ribosome bound to IDB-002 stalled on FPAK-containing nascent chain	ELECTRON MICROSCOPY	2.2
8JDK	Structure of the Human cytoplasmic Ribosome with human tRNA Asp(ManQ34) and mRNA(GAU)	ELECTRON MICROSCOPY	2.26
8G5Y	mRNA decoding in human is kinetically and structurally distinct from bacteria (IC state)	ELECTRON MICROSCOPY	2.29
9S3D	NAC bound human RNC with 58 amino acid ARF1-linker	ELECTRON MICROSCOPY	2.32
9MNC	Human 80S ribosome bound to small molecule SW393071	ELECTRON MICROSCOPY	2.33
9RPV	Structure of the ZAK-bound human disome	ELECTRON MICROSCOPY	2.35
9S3B	NMT1-NAC bound human RNC with 58 amino acid ARF1-linker - State 1	ELECTRON MICROSCOPY	2.38
8K2C	Cryo-EM structure of the human 80S ribosome with Tigecycline	ELECTRON MICROSCOPY	2.4
8XSX	Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA, SERBP1 and eEF2	ELECTRON MICROSCOPY	2.4
9SPF	CRYO-EM STRUCTURE OF HUMAN 80S RIBOSOME WITH A/P/E-SITE TRNA AND MRNA CONTAINING …	ELECTRON MICROSCOPY	2.4
9SPI	CRYO-EM STRUCTURE OF HUMAN 80S RIBOSOME WITH A/P/E-SITE TRNA AND MRNA CONTAINING URIDINE	ELECTRON MICROSCOPY	2.4
8JDL	Structure of the Human cytoplasmic Ribosome with human tRNA Tyr(GalQ34) and mRNA(UAU) …	ELECTRON MICROSCOPY	2.42
9PKD	In situ CHX and HHT treated 80S consensus ribosome	ELECTRON MICROSCOPY	2.42
9S3C	NMT1-NAC bound human RNC with 58 amino acid ARF1-linker - State 2	ELECTRON MICROSCOPY	2.42
9QLO	NMT1-NAC bound human RNC with full length ARF1 - State 1	ELECTRON MICROSCOPY	2.47
9P8B	In situ human eEF1A-A/T-P-E state 80S ribosome	ELECTRON MICROSCOPY	2.48
9WW4	human 80S ribosome non-rotated state	ELECTRON MICROSCOPY	2.48
7XNY	High resolution cry-EM structure of the human 80S ribosome from SNORD127+/- Kasumi-1 cells	ELECTRON MICROSCOPY	2.5
8JDJ	Structure of the Human cytoplasmic Ribosome with human tRNA Asp(Q34) and mRNA(GAU)	ELECTRON MICROSCOPY	2.5
9RUC	WT-HEK 80S ribosome bound to H2B mRNA (WT-H2B)	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15880-F1	82.10	0.63

Human Protein Atlas

Protein class: Ribosomal proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutated cancer genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; endoplasmic reticulum

Antibody reliability (HPA): IH approved · IF approved

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 (12)

Type	Positions
Phosphothreonine	270, 252
N6-acetyllysine	275, 263
Phosphoserine	281, 264
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	54, 58, 275
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	275
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	275
N-acetylalanine	2

Mutagenesis-validated functional residues (3)

Position	Phenotype
54–58	abolished ubiquitination and degradation by rnf10.
58	does not affect readthrough on the poly(a)-stall sequences; when associated with r-275.
275	does not affect readthrough on the poly(a)-stall sequences; when associated with r-58.

Function

Pathways and Gene Ontology

Reactome pathways

17 curated (TAS) of 58; 13 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

58 pathways:

ID	Pathway	Evidence
R-HSA-9735869	SARS-CoV-1 modulates host translation machinery ⚕	curated
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery ⚕	curated
R-HSA-192823	Viral mRNA Translation ⚕	curated
R-HSA-72689	Formation of a pool of free 40S subunits	curated
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex	curated
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit	curated
R-HSA-9684482	IFIT antiviral response	curated
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression	curated
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol	curated
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	curated
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	curated
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	curated
R-HSA-8876725	Protein methylation	curated
R-HSA-3214858	RMTs methylate histone arginines	curated
R-HSA-72702	Ribosomal scanning and start codon recognition	curated
R-HSA-72649	Translation initiation complex formation	curated
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-168255	Influenza Infection ⚕	—
R-HSA-168273	Influenza Viral RNA Transcription and Replication ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9678108	SARS-CoV-1 Infection ⚕	—
R-HSA-9692914	SARS-CoV-1-host interactions ⚕	—
R-HSA-9694516	SARS-CoV-2 Infection ⚕	—
R-HSA-9705683	SARS-CoV-2-host interactions ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-72662	Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	—
R-HSA-422475	Axon guidance	—
R-HSA-72737	Cap-dependent Translation Initiation	—
R-HSA-9711097	Cellular response to starvation	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—
R-HSA-1266738	Developmental Biology	—
R-HSA-156842	Eukaryotic Translation Elongation	—
R-HSA-72613	Eukaryotic Translation Initiation	—
R-HSA-72764	Eukaryotic Translation Termination	electronic
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors	electronic
R-HSA-1430728	Metabolism	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-9675108	Nervous system development	—
R-HSA-927802	Nonsense-Mediated Decay (NMD)	—
R-HSA-156902	Peptide chain elongation	electronic
R-HSA-597592	Post-translational protein modification	—
R-HSA-9010553	Regulation of expression of SLITs and ROBOs	electronic
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency	electronic
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane	electronic
R-HSA-2408522	Selenoamino acid metabolism	—
R-HSA-2408557	Selenocysteine synthesis	electronic
R-HSA-376176	Signaling by ROBO receptors	—
R-HSA-72766	Translation	—
R-HSA-6790901	rRNA modification in the nucleus and cytosol	electronic
R-HSA-72312	rRNA processing	—
R-HSA-8868773	rRNA processing in the nucleus and cytosol	—

MSigDB gene sets: 251 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, LU_IL4_SIGNALING, SWEET_KRAS_ONCOGENIC_SIGNATURE, MODULE_151, GNF2_TPT1, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GCM_NPM1, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, HSIAO_HOUSEKEEPING_GENES, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, DOANE_RESPONSE_TO_ANDROGEN_DN

GO Biological Process (3): cytoplasmic translation (GO:0002181), translation (GO:0006412), positive regulation of ubiquitin-protein transferase activity (GO:0051443)

GO Molecular Function (7): RNA binding (GO:0003723), mRNA binding (GO:0003729), structural constituent of ribosome (GO:0003735), fibroblast growth factor binding (GO:0017134), enzyme binding (GO:0019899), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), extracellular exosome (GO:0070062), ribosome (GO:0005840), small ribosomal subunit (GO:0015935), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
rRNA processing in the nucleus and cytosol	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
Chromatin modifying enzymes	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Post-translational protein modification	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
Antimicrobial mechanism of IFN-stimulated genes	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1

GO top-level categories

33 GO namespaces:

Category	Terms
cellular anatomical structure	4
ribosome	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
ubiquitin-protein transferase activity	1
positive regulation of protein ubiquitination	1
positive regulation of catalytic activity	1
regulation of ubiquitin-protein transferase activity	1
nucleic acid binding	1
RNA binding	1
structural molecule activity	1
growth factor binding	1
protein binding	1
cell adhesion molecule binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
extracellular vesicle	1
intracellular membraneless organelle	1
ribosomal subunit	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of ubiquitin-protein transferase activity	BP	direct assay
cytosolic ribosome	CC	direct assay
cytosolic small ribosomal subunit	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
membrane	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	high-throughput assay
RNA binding	MF	high-throughput assay
cadherin binding	MF	high-throughput assay
enzyme binding	MF	physical interaction
fibroblast growth factor binding	MF	physical interaction
mRNA binding	MF	direct assay
structural constituent of ribosome	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,486 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS2	RPS3	P23396	814
RPS2	RPS8	P09058	782
RPS2	RPS11	P04643	769
RPS2	RPS19	P39019	738
RPS2	RPS16	P17008	726
RPS2	RPS10	P46783	726
RPS2	HTATSF1	O43719	723
RPS2	RPS13	P19116	719
RPS2	RPL36	Q9Y3U8	718
RPS2	RPS5	P46782	717
RPS2	RPL4	P36578	714
RPS2	RPS18	P25232	713
RPS2	RPL5	P46777	712
RPS2	RPL14	P50914	711
RPS2	RPS20	P17075	700

IntAct

Human interaction partners of RPS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

28 partners by confidence:

Partner	Interaction type	MIscore	Records
PRMT3	physical association	0.810	6
NAT10	physical association	0.670	1
LRRK2	phosphorylation reaction	0.640	1
PDCD2	physical association	0.620	1
RPS9	physical association	0.560	1
GABARAPL2	physical association	0.550	1
MPHOSPH10	association	0.530	3
AKT1	physical association	0.530	2
NAP1L5	association	0.530	2
RPS18	association	0.530	1
ANXA7	physical association	0.370	1
CDKN1A	physical association	0.370	1
DNM2	physical association	0.370	1
GADD45A	physical association	0.370	1
GRB7	physical association	0.370	1
GSK3B	physical association	0.370	1
MLH1	physical association	0.370	1
SMN1	physical association	0.370	1
SOX5	physical association	0.370	1
TK1	physical association	0.370	1
NOL10	association	0.350	2
ZKSCAN8	association	0.350	1
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
PTPN11	proximity	0.270	1
SPOP	proximity	0.270	1
TP53	proximity	0.270	1
MPP3	physical association	0.000	1

BioGRID (1,193 interactions; top human partners by supporting records in a sample of 600 records): PRMT3 (Biochemical Activity; 7 records), RPS10 (Affinity Capture-MS; 5 records), RPS3 (Affinity Capture-MS; 5 records), C1QBP (Affinity Capture-MS; 4 records), GTF3C2 (Affinity Capture-MS; 4 records), LARP7 (Affinity Capture-MS; 4 records), NAT10 (Affinity Capture-MS; 4 records), PDCD2 (Affinity Capture-MS; 4 records), PDCD2L (Affinity Capture-MS; 4 records), RIOK1 (Affinity Capture-MS; 4 records), RPL26L1 (Affinity Capture-MS; 4 records), RPS17 (Affinity Capture-MS; 4 records), RPS3A (Affinity Capture-MS; 4 records), RPS5 (Affinity Capture-MS; 4 records), RPSA (Affinity Capture-MS; 4 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
RPS2	“form complex”	“40S cytosolic small ribosomal subunit”	binding
“Host translation inhibitor nsp1”	“down-regulates activity”	RPS2	binding

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ Nop56p-associated pre-rRNA complex	104	LUC7L2, NCL, RPL27, RPL29, RPL39, RPL7, RPS23, RPS6, MYBBP1A, RPL21, RPL28, RPL5, RPS9, U2AF2, LYAR, RPL13, RPL23, RPL23A, RPL35A, RPL4, RPS24, HNRNPA1, EBNA1BP2, RPLP1, RPS17, U2AF1, DHX9, RPL30, SCYL2, RPL11, RPS11, NOLC1, RPL12, RPL14, RPL17, RPL19, RPL32, RPS13, RPS8, NOP58, RPL36A, RPLP2, RPS2, RPS29, SRP14, TCOF1, TUFM, ACTG2, RBM28, RPL10, RPL37A, RPS12, RPS7, TUBB1, BRIX1, DDX21, GNL3, IGF2BP1, ILF2, RPL10A, RPL15, RPLP0, EEF2, HNRNPU, NOP56, RPL26, RPL3, RPS14, RPS16, RSL1D1, ACTA2, EEF1A1, H1-3, RPL24, RPL6, RPL8, SRPK1, TOP1, FBL, HNRNPM, RPL13A, RPL31, RPL7A, RPS18, H1-10, ILF3, NPM1, RPS15A, TUBA1A, YBX1, H2BC14, PWP1, RPL18A, RPL22, RPL27A, RPS15, RPS3A, SLC25A5, NAP1L1, RPL18, RPL35, RPL36, RPL9, SNU13
Ribosome, cytoplasmic	80	RPS12, RPS27A, RPL12, RPSA, RPL24, RPL27A, RPL37, RPLP0, RPS15, RPS3A, RPL10, RPL15, RPL23A, RPL36A, RPS15A, RPS19, RPL17, RPL6, RPLP1, RPS23, RPS28, RPS6, RPL29, RPL35A, RPS4Y1, RPS7, RPS10, RPL13, RPL28, RPL3, RPL30, RPL36, RPS27, RPS9, RPL14, RPL26, RPS17, RPS2, RPL13A, RPL27, RPL35, RPL38, RPL41, RPS18, RPS26, RPL22, RPL4, RPL5, RPS11, UBA52, RPL18, RPL7A, RPL19, RPL37A, RPL8, RPS14, RPS20, FAU, RPL34, RPL7, RPS21, RPS25, RPS5, RPS13, RPS24, RPS29, RPS8, RPL39, RPL9, RPLP2, RPS3, RPL10A, RPL11, RPL18A, RPL23, RPL31, RPS16, RPS4X, RPL21, RPL32
40S ribosomal subunit, cytoplasmic	33	RPS21, RPS27, RPS29, RPS4Y1, RPS17, RPS27A, RPS3, RPS5, RPS9, RPS6, FAU, RPS12, RPS19, RPS10, RPS14, RPS18, RPS4X, RPS13, RPS26, RPS3A, RPS8, RPSA, RPS11, RPS15A, RPS16, RPS20, RPS23, RPS24, RPS25, RPS28, RPS15, RPS7, RPS2
40S ribosomal subunit, cytoplasmic	31	RPS3A, FAU, RPS11, RPS12, RPS24, RPS27A, RPS10, RPS20, RPS5, RPS6, RPS14, RPS16, RPS19, RPS28, RPS4X, RPS15, RPS21, RPS25, RPS8, RPS7, RPS13, RPSA, RPS17, RPS18, RPS2, RPS23, RPS29, RPS3, RPS9, RPS15A, RPS26

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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
Metabolism of RNA	6	11.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagy	5	20.4×	1e-03

Disease & clinical

Genetic variants

Variant evidence for RPS2: 39 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 287):

Position(s)	Effect	Δscore	Sites
16:1962271–1962272	acceptor_loss	1.0000	5
16:1962495–1962496	donor_loss	1.0000	5
16:1962657–1962658	acceptor_loss	1.0000	6
16:1962734–1962735	donor_loss	1.0000	5
16:1962760	donor_gain	1.0000
16:1962910–1962911	acceptor_loss	1.0000	5
16:1963147–1963148	donor_loss	1.0000	4
16:1963257	acceptor_gain	1.0000
16:1963257–1963258	acceptor_loss	1.0000	4
16:1963264	acceptor_gain	1.0000

AlphaMissense

1,493 missense substitutions predicted likely pathogenic (of 1,878 scored), across 278 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M216	9	0.946	0.999
M110	9	0.940	0.995
D221	8	1.000	1.000
F124	8	0.999	1.000
D132	8	0.998	1.000
H178	8	0.998	1.000
N235	8	0.997	1.000
D104	8	0.996	1.000
H136	8	0.996	1.000
F236	8	0.995	1.000
F127	8	0.985	1.000
F97	8	0.965	0.999
D95	8	0.952	0.997
F261	8	0.942	0.995
D254	8	0.932	0.995
F29	8	0.929	0.993
D271	8	0.910	0.991
D72	8	0.881	0.990
H277	8	0.834	0.970
E146	7	1.000	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	4.55e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	6.2e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	2.96e-05
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	0.000368
Lung Adenocarcinoma (validation)	unfavorable	0.000731
Bladder Urothelial Carcinoma (TCGA)	unfavorable	0.000952

Disease associations

OMIM: gene MIM:603624 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST006061_81	Atrial fibrillation	4e-14
GCST010796_2743	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066954 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.09	Kd	80.43	nM	CHEMBL3752910
7.09	ED50	80.43	nM	CHEMBL3752910
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.74	Kd	1825	nM	CHEMBL5653589
5.74	ED50	1825	nM	CHEMBL5653589
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

48 with measured affinity, of 209 total; 28 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149293: Binding affinity to human RPS2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0804	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149293: Binding affinity to human RPS2 incubated for 45 mins by Kinobead based pull down assay	kd	1.8254	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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, affects cotreatment	6
sodium arsenite	affects binding, decreases reaction, decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
chloropicrin	decreases expression	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
diisononyl phthalate	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1
arsenite	increases reaction, affects binding	1
lead nitrate	affects cotreatment, increases expression	1
perfluorooctanoic acid	decreases expression	1
butylbenzyl phthalate	affects cotreatment, increases expression	1
cupric oxide	increases expression	1
epigallocatechin gallate	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
tamibarotene	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	increases expression	1
CD 437	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	increases expression	1
K 7174	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RPS2 across ~30M SureChEMBL compounds — explore on Sugi Predict.