RPL21

Summary

RPL21 (ribosomal protein L21, HGNC:10313) is a protein-coding gene on chromosome 13q12.2, encoding Large ribosomal subunit protein eL21 (P46778). Component of the large ribosomal subunit. 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 60S subunit. The protein belongs to the L21E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6144 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypotrichosis 12 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 36 total — 1 pathogenic
• GTEx eGene: eQTL in 8 tissues, sQTL in 11 (q < 0.05)
• Phenotypes (HPO): 18
• 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)
• MANE Select transcript: NM_000982
• Interaction hub: 2,952 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10313
Approved symbol	RPL21
Name	ribosomal protein L21
Location	13q12.2
Locus type	gene with protein product
Status	Approved
Aliases	L21, FLJ27458, MGC71252, MGC104274, MGC104275, DKFZp686C06101, eL21
Ensembl gene	ENSG00000122026
Ensembl biotype	protein_coding
OMIM	603636
Entrez	6144

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 29 protein_coding, 9 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000311549

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 7, TSL 3: 1, TSL 5: 1

ENST00000311549, ENST00000272274, ENST00000319826, ENST00000326092, ENST00000461690, ENST00000466550, ENST00000473558, ENST00000483765, ENST00000485756, ENST00000493317, ENST00000907071, ENST00000907072, ENST00000939429, ENST00000939430, ENST00000939431, ENST00000939432, ENST00000939433, ENST00000939434, ENST00000939435, ENST00000984462, ENST00001025525, ENST00001061072, ENST00001061074, ENST00001061075, ENST00001061080, ENST00001098057, ENST00001098058, ENST00001098059, ENST00001098060, ENST00001098061, ENST00001098062, ENST00001098063, ENST00001098064, ENST00001118318, ENST00001126158, ENST00001126159, ENST00001126160, ENST00001126161, ENST00001126162, ENST00001126163, ENST00001132315

RefSeq mRNA: 1 — MANE Select: NM_000982 NM_000982

CCDS: CCDS9320

Canonical transcript exons

ENST00000311549 — 6 exons

Exon	Start	End
ENSE00001222524	27256436	27256568
ENSE00001830734	27251558	27251585
ENSE00003492826	27256184	27256334
ENSE00003545702	27254220	27254281
ENSE00003607298	27253765	27253843
ENSE00003688877	27255242	27255354

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.1144 / max 541.1070, expressed in 1820 samples.

Highest expression (Bgee): calcaneal tendon, embryo, ganglionic eminence, colonic epithelium, primary visual cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RPL21 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	6.2e-38	-0.77	13:27175221:T:C
Esophagus Mucosa	sqtl	2.8e-36	+1.25	13:27217250:T:C
Cells EBV-transformed lymphocytes	sqtl	3.0e-36	+1.38	13:27251765:T:C
Whole Blood	eqtl	2.4e-21	-0.30	13:27242863:T:C
Heart Left Ventricle	sqtl	1.7e-18	+1.19	13:27251765:T:C
Colon Transverse	sqtl	3.6e-18	-0.71	13:27251765:T:C
Testis	sqtl	1.1e-13	-1.04	13:27251765:T:C
Liver	sqtl	2.1e-08	+1.00	13:27175221:T:C
Muscle Skeletal	eqtl	3.1e-08	-0.21	13:27255876:A:G
Brain Cerebellum	sqtl	3.8e-07	-0.66	13:27234102:G:A
Muscle Skeletal	sqtl	4.4e-06	-0.30	13:27234102:G:A
Brain Cerebellar Hemisphere	sqtl	3.6e-05	-0.49	13:27234102:G:A
Stomach	eqtl	5.7e-03	+0.21	13:27217250:T:C
Adipose Subcutaneous	eqtl	5.7e-03	+0.11	13:27251765:T:C
Esophagus Muscularis	eqtl	2.1e-02	+0.29	13:27987104:C:T
Artery Tibial	eqtl	4.0e-02	+0.21	13:26703020:G:GTTTGTT
Skin Not Sun Exposed Suprapubic	eqtl	4.2e-02	+0.06	13:27755885:G:A
Cells Cultured fibroblasts	eqtl	4.4e-02	+0.05	13:27155272:A:G
Lung	sqtl	4.9e-02	-0.20	13:27168953:G:A

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
134511	15.9901	1794
134508	14.5840	1788
134510	5.7124	1666
134509	0.8843	460
111713	0.3784	162
134513	0.3277	152
134512	0.2375	85

Top tissues by expression

showing 100 of 154 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.88	gold quality
embryo	UBERON:0000922	99.84	gold quality
ganglionic eminence	UBERON:0004023	99.84	gold quality
colonic epithelium	UBERON:0000397	99.83	gold quality
primary visual cortex	UBERON:0002436	99.83	gold quality
endometrium	UBERON:0001295	99.82	gold quality
cortical plate	UBERON:0005343	99.82	gold quality
lymph node	UBERON:0000029	99.81	gold quality
ventricular zone	UBERON:0003053	99.80	gold quality
monocyte	CL:0000576	99.78	gold quality
leukocyte	CL:0000738	99.78	gold quality
ovary	UBERON:0000992	99.78	gold quality
superior frontal gyrus	UBERON:0002661	99.78	gold quality
left ovary	UBERON:0002119	99.77	gold quality
islet of Langerhans	UBERON:0000006	99.76	gold quality
uterus	UBERON:0000995	99.75	gold quality
bone marrow	UBERON:0002371	99.75	gold quality
right ovary	UBERON:0002118	99.74	gold quality
tonsil	UBERON:0002372	99.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.74	gold quality
body of pancreas	UBERON:0001150	99.73	gold quality
pancreas	UBERON:0001264	99.73	gold quality
granulocyte	CL:0000094	99.72	gold quality
bone marrow cell	CL:0002092	99.72	gold quality
endocervix	UBERON:0000458	99.72	gold quality
cortex of kidney	UBERON:0001225	99.72	gold quality
mammary gland	UBERON:0001911	99.72	gold quality
fallopian tube	UBERON:0003889	99.72	gold quality
thoracic mammary gland	UBERON:0005200	99.72	gold quality
body of uterus	UBERON:0009853	99.72	gold quality
uterine cervix	UBERON:0000002	99.71	gold quality
skin of abdomen	UBERON:0001416	99.71	gold quality
zone of skin	UBERON:0000014	99.70	gold quality
thyroid gland	UBERON:0002046	99.70	gold quality
right lung	UBERON:0002167	99.70	gold quality
prostate gland	UBERON:0002367	99.70	gold quality
rectum	UBERON:0001052	99.69	gold quality
left lobe of thyroid gland	UBERON:0001120	99.69	gold quality
myometrium	UBERON:0001296	99.69	gold quality
right uterine tube	UBERON:0001302	99.69	gold quality
skin of leg	UBERON:0001511	99.69	gold quality
adenohypophysis	UBERON:0002196	99.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.69	gold quality
pituitary gland	UBERON:0000007	99.68	gold quality
mucosa of stomach	UBERON:0001199	99.68	gold quality
placenta	UBERON:0001987	99.68	gold quality
cerebellum	UBERON:0002037	99.68	gold quality
spleen	UBERON:0002106	99.68	gold quality
cerebellar cortex	UBERON:0002129	99.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.68	gold quality
ectocervix	UBERON:0012249	99.68	gold quality
lower esophagus	UBERON:0013473	99.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.68	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.68	gold quality
vagina	UBERON:0000996	99.67	gold quality
adipose tissue	UBERON:0001013	99.67	gold quality
right lobe of thyroid gland	UBERON:0001119	99.67	gold quality
smooth muscle tissue	UBERON:0001135	99.67	gold quality
left uterine tube	UBERON:0001303	99.67	gold quality
artery	UBERON:0001637	99.67	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.67	gold quality
cerebellar hemisphere	UBERON:0002245	99.67	gold quality
popliteal artery	UBERON:0002250	99.67	gold quality
tibial artery	UBERON:0007610	99.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.67	gold quality
vermiform appendix	UBERON:0001154	99.66	gold quality
colon	UBERON:0001155	99.66	gold quality
left coronary artery	UBERON:0001626	99.66	gold quality
nucleus accumbens	UBERON:0001882	99.66	gold quality
gall bladder	UBERON:0002110	99.66	gold quality
omental fat pad	UBERON:0010414	99.66	gold quality
peripheral nervous system	UBERON:0000010	99.65	gold quality
aorta	UBERON:0000947	99.65	gold quality
nerve	UBERON:0001021	99.65	gold quality
tibial nerve	UBERON:0001323	99.65	gold quality
intestine	UBERON:0000160	99.64	gold quality
esophagus	UBERON:0001043	99.64	gold quality
body of stomach	UBERON:0001161	99.64	gold quality
urinary bladder	UBERON:0001255	99.64	gold quality
muscle tissue	UBERON:0002385	99.64	gold quality
metanephros cortex	UBERON:0010533	99.64	gold quality
ascending aorta	UBERON:0001496	99.63	gold quality
thoracic aorta	UBERON:0001515	99.63	gold quality
substantia nigra	UBERON:0002038	99.63	gold quality
lung	UBERON:0002048	99.63	gold quality
descending thoracic aorta	UBERON:0002345	99.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.63	gold quality
adult mammalian kidney	UBERON:0000082	99.62	gold quality
saliva-secreting gland	UBERON:0001044	99.62	gold quality
skeletal muscle tissue	UBERON:0001134	99.62	gold quality
fundus of stomach	UBERON:0001160	99.62	gold quality
amygdala	UBERON:0001876	99.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.62	gold quality
transverse colon	UBERON:0001157	99.61	gold quality
minor salivary gland	UBERON:0001830	99.61	gold quality
small intestine	UBERON:0002108	99.61	gold quality
upper lobe of left lung	UBERON:0008952	99.61	gold quality
right coronary artery	UBERON:0001625	99.60	gold quality
esophagus mucosa	UBERON:0002469	99.60	gold quality
stomach	UBERON:0000945	99.59	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	11806.82
E-HCAD-9	yes	10464.16
E-CURD-46	yes	10081.12
E-MTAB-8142	yes	8398.85
E-ENAD-17	yes	3839.27
E-CURD-122	yes	99.21
E-MTAB-9221	yes	56.10
E-MTAB-6678	yes	44.54
E-CURD-112	yes	32.99
E-MTAB-9067	yes	25.61
E-MTAB-10042	yes	14.83
E-GEOD-135922	yes	13.83
E-HCAD-35	yes	9.75
E-GEOD-137537	yes	5.98
E-HCAD-25	yes	4.19

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 65 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	4290.5	not detected
Bone marrow	tissue	3899.5	medium
Lymph node	tissue	3341.9	high
Breast	tissue	3311.9	medium
Tonsil	tissue	3093.0	high
Vagina	tissue	2558.1	high
Pancreas	tissue	2484.6	medium
Thymus	tissue	2234.9
Skeletal muscle	tissue	2070.5	high
Salivary gland	tissue	1931.2	medium
Fallopian tube	tissue	1850.6	medium
Epididymis	tissue	1782.5	low
Skin 1	tissue	1778.6	high
Thyroid gland	tissue	1760.4	medium
Cervix	tissue	1736.1	medium
Tongue	tissue	1731.8
Urinary bladder	tissue	1727.2	high
Rectum	tissue	1688.0	high
Spleen	tissue	1646.6	medium
Endometrium 1	tissue	1626.3	high
Colon	tissue	1603.5	high
Pituitary gland	tissue	1602.2
Liver	tissue	1503.0	low
Kidney	tissue	1412.8	high
Seminal vesicle	tissue	1378.7	medium
Esophagus	tissue	1351.4	high
Smooth muscle	tissue	1301.5	medium
Appendix	tissue	1297.0	high
Heart muscle	tissue	1225.6	medium
Adrenal gland	tissue	1197.1	medium
Placenta	tissue	1169.7	medium
Stomach 1	tissue	1161.6	medium
Duodenum	tissue	1151.0	high
Gallbladder	tissue	1135.3	high
Prostate	tissue	1108.7	medium
Lung	tissue	1107.5	low
Parathyroid gland	tissue	1098.8
Small intestine	tissue	1094.0	high
Adipose tissue	tissue	1043.7	low
Retina	tissue	966.4
Hypothalamus	tissue	467.4
Testis	tissue	411.2	medium
Spinal cord	tissue	399.0
Medulla oblongata	tissue	398.6
Basal ganglia	tissue	395.5	low
Thalamus	tissue	392.9
Nucleus accumbens	tissue	365.2
Midbrain	tissue	357.0
Substantia nigra	tissue	357.0
Pons	tissue	354.6
Amygdala	tissue	353.6
Cerebral cortex	tissue	339.8	medium
Cerebellum	tissue	334.6	medium
Putamen	tissue	295.2
Choroid plexus	tissue	289.6
Locus coeruleus	tissue	267.4
Hippocampus	tissue	256.4	medium
Hippocampal formation	tissue	256.4
Retrosplenial cortex	tissue	245.2
Occipital cortex	tissue	205.6

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Blood vessel (2833.5), Paraventricular nucleus (467.4), Temporal white matter (428.8), White matter (428.8), Cerebellar white matter (404.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000311549 — one region, missense o/e 0.57. 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): PCI-6A (-4.284), HCT-15 (-4.203), PCI-4B (-4.171), TOV-21G (-4.153), AGS (-4.124), KARPAS-299 (-4.096), DBTRG-05MG (-4.094), LXF-289 (-4.047), A-172 (-4.046), KATO III (-4.043), MHH-ES-1 (-4.035), TGW (-4.032), FaDu (-4.001), OV-90 (-3.996), A549 (-3.994).

Literature-anchored findings (GeneRIF, showing 2)

• The cause of hereditary hypotrichosis in this family was identified as a c.95G>A (p.Arg32Gln) mutation in the ribosomal protein L21. (PMID:21412954)
• The ribosomal protein eL21 interacts with the protein lysine methyltransferase SMYD2 and regulates its steady state levels. (PMID:34147559)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpl21	ENSDARG00000010516
drosophila_melanogaster	RpL21	FBGN0032987
caenorhabditis_elegans		WBGENE00004433

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 maripaludis C7	A6VI82	100.0%	Diamond
Methanococcus maripaludis C6	A9A8J8	100.0%	Diamond
Saccharolobus islandicus L.S.2.15	C3MQ30	100.0%	Diamond
Saccharolobus islandicus M.14.25	C3MVE8	100.0%	Diamond
Saccharolobus islandicus M.16.27	C3N5P7	100.0%	Diamond
Saccharolobus islandicus Y.N.15.51	C3NHD9	100.0%	Diamond
Saccharolobus islandicus M.16.4	C4KHC6	100.0%	Diamond
Oryctolagus cuniculus	G1SHQ2	100.0%	Diamond
Sus scrofa	P49666	100.0%	Diamond
Capra hircus	A5JSS2	99.4%	Diamond
Mus musculus	O09167	99.4%	Diamond
Schizosaccharomyces pombe 972h-	O42706	99.4%	Diamond
Chinchilla lanigera	Q6QN05	99.4%	Diamond
Methanococcus maripaludis C5	A4G096	99.0%	Diamond
Saccharolobus islandicus Y.G.57.14	C3NEB3	99.0%	Diamond
Rattus norvegicus	P20280	98.8%	Diamond
Saccharomyces cerevisiae S288C	Q02753	98.8%	Diamond
Methanococcus maripaludis S2	Q6M125	97.9%	Diamond
Arabidopsis thaliana	Q43291	97.6%	Diamond
Methanosarcina barkeri str. Fusaro	Q466S9	93.8%	Diamond
Methanosarcina acetivorans C2A	Q8TQU3	93.8%	Diamond
Saccharolobus solfataricus P2	Q9UXE0	93.1%	Diamond
Methanococcus vannielii SB	A6UR83	91.8%	Diamond
Xenopus laevis	P49628	90.9%	Diamond
Methanosarcina mazei Go1	Q8PU21	90.7%	Diamond
Methanoculleus marisnigri JR1	A3CWY7	83.3%	Diamond
Methanosphaerula palustris E1-9c	B8GEV3	83.3%	Diamond
Candida albicans SC5314	A0A1D8PGY0	82.5%	Diamond
Methanoregula boonei 6A8	A7I9H8	80.2%	Diamond
Sulfurisphaera tokodaii str. 7	Q975F2	79.6%	Diamond
Methanococcoides burtonii DSM 6242	Q12XH4	78.4%	Diamond
Methanospirillum hungatei JF-1	Q2FS99	78.1%	Diamond
Methanococcus aeolicus Nankai-3	A6UT27	75.0%	Diamond
Sulfolobus acidocaldarius DSM 639	Q4JB11	71.3%	Diamond
Methanocaldococcus jannaschii DSM 2661	P54013	71.0%	Diamond
Pyura stolonifera	P49667	70.9%	Diamond
Methanopyrus kandleri AV19	Q8TUU3	70.5%	Diamond
Staphylothermus marinus F1	A3DML6	68.1%	Diamond
Ignicoccus hospitalis KIN4/I	A8AAK8	67.3%	Diamond
Aeropyrum pernix K1	P58077	58.8%	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
USP12-DT	ncRNA	100874071
SNORD102	snoRNA	26771
SNORA27	snoRNA	619499
RASL11A	protein-coding	387496
USP12-AS1	ncRNA	100874070
LINC00412	ncRNA	102723332
USP12	protein-coding	219333

Protein

Protein identifiers

Large ribosomal subunit protein eL21 — P46778 (reviewed: P46778)

Alternative names: 60S ribosomal protein L21

All UniProt accessions (5): G3V1B3, M0R181, M0R3I5, P46778, Q6IAX2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.

Subunit / interactions. Component of the large ribosomal subunit.

Subcellular location. Cytoplasm. Cytosol. Endoplasmic reticulum.

Disease relevance. Hypotrichosis 12 (HYPT12) [MIM:615885] A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT12 patients have normal scalp hair density at birth. Hair loss begins during the first 6 months of life and gradually progresses to nearly complete loss of scalp hair. The remaining hairs grow slowly and are thin, sparse, dry, and fragile. Body hair, axillary and pubic hair, eyebrows and eyelashes are also sparse or absent. HYPT12 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the eukaryotic ribosomal protein eL21 family.

RefSeq proteins (1): NP_000973* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001147	Ribosomal_eL21	Family
IPR008991	Translation_prot_SH3-like_sf	Homologous_superfamily
IPR018259	Ribosomal_eL21_CS	Conserved_site
IPR036948	Ribosomal_eL21_sf	Homologous_superfamily

Pfam: PF01157

UniProt features (34 total): helix 11, sequence conflict 7, strand 7, turn 2, compositionally biased region 2, sequence variant 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

showing 30 of 183 structures by resolution:

PDB	Title	Method	Resolution (Å)
8A3D	Human mature large subunit of the ribosome with eIF6 and homoharringtonine bound	ELECTRON MICROSCOPY	1.67
8GLP	mRNA decoding in human is kinetically and structurally distinct from bacteria (Consensus …	ELECTRON MICROSCOPY	1.67
8QYX	Human 60S ribosomal subunit	ELECTRON MICROSCOPY	1.78
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
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
8QFD	UFL1 E3 ligase bound 60S ribosome	ELECTRON MICROSCOPY	2.2
8YOP	Cryo-EM structure of the human 80S ribosome with 4 um Tigecycline	ELECTRON MICROSCOPY	2.2
9GUL	Structure of FLuc-XBP1u+ stalled human 60S ribosome nascent chain complex	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
7OW7	EIF6-bound large subunit of the human ribosome	ELECTRON MICROSCOPY	2.4
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
8FKV	Human nucleolar pre-60S ribosomal subunit (State D1)	ELECTRON MICROSCOPY	2.47
9QLO	NMT1-NAC bound human RNC with full length ARF1 - State 1	ELECTRON MICROSCOPY	2.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46778-F1	94.12	0.91

Human Protein Atlas

Protein class: Ribosomal proteins, Predicted intracellular proteins, Disease related genes, Human disease related genes, Essential proteins

Protein evidence: Evidence at protein level

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

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 40; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

40 pathways:

ID	Pathway	Evidence
R-HSA-192823	Viral mRNA Translation ⚕	curated
R-HSA-72689	Formation of a pool of free 40S subunits	curated
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit	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-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-9824446	Viral Infection Pathways ⚕	—
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-1266738	Developmental Biology	—
R-HSA-156842	Eukaryotic Translation Elongation	—
R-HSA-72613	Eukaryotic Translation Initiation	—
R-HSA-72764	Eukaryotic Translation Termination	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-9010553	Regulation of expression of SLITs and ROBOs	electronic
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency	electronic
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	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-72312	rRNA processing	—
R-HSA-8868773	rRNA processing in the nucleus and cytosol	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (5): cytoplasmic translation (GO:0002181), translation (GO:0006412), striated muscle contraction (GO:0006941), spermatogenesis (GO:0007283), negative regulation of myoblast fusion (GO:1901740)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (10): fibrillar center (GO:0001650), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), cytosolic ribosome (GO:0022626), synapse (GO:0045202), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Translation	3
Ribosome-associated quality control	3
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

30 GO namespaces:

Category	Terms
cellular anatomical structure	4
ribosome	2
cytoplasm	2
translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
muscle contraction	1
developmental process involved in reproduction	1
male gamete generation	1
myoblast fusion	1
negative regulation of syncytium formation by plasma membrane fusion	1
regulation of myoblast fusion	1
nucleic acid binding	1
structural molecule activity	1
binding	1
nucleolus	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
large ribosomal subunit	1
cytosolic ribosome	1
cytosol	1
cell junction	1
intracellular membraneless organelle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
cytosolic large ribosomal subunit	CC	direct assay
cytosolic ribosome	CC	direct assay
endoplasmic reticulum	CC	direct assay
fibrillar center	CC	direct assay
membrane	CC	high-throughput assay
RNA binding	MF	high-throughput assay
structural constituent of ribosome	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,952 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL21	RPL28	P46779	958
RPL21	RPS9	P46781	956
RPL21	RPL27A	P46776	949
RPL21	RPS5	P46782	944
RPL21	RPS29	P30054	940
RPL21	RPS10	P46783	935
RPL21	RPL5	P46777	913
RPL21	SURF6	O75683	739
RPL21	RPL22	P35268	732
RPL21	RPL31	P12947	680
RPL21	RPS20	P17075	664
RPL21	RPL9	P32969	664
RPL21	RPL14	P50914	664
RPL21	MED22	Q15528	662
RPL21	RPS2	P15880	650

IntAct

Human interaction partners of RPL21 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
LRRK2	phosphorylation reaction	0.440	1
CAVIN1	physical association	0.400	1
CENPE	physical association	0.400	1
DLG5	physical association	0.400	1
DNAH6	physical association	0.400	1
SAXO4	physical association	0.400	1
CTNNB1	physical association	0.000	1
EEF1D	physical association	0.000	1
HNRNPA1	physical association	0.000	1
L1RE1	physical association	0.000	1
NR2F6	physical association	0.000	1
PIM2	physical association	0.000	1
SOD2	physical association	0.000	1

BioGRID (558 interactions; top human partners by supporting records): RPL29 (Cross-Linking-MS (XL-MS); 10 records), RPL18 (Co-fractionation; 6 records), RPL5 (Co-fractionation; 5 records), RPL18A (Co-fractionation; 4 records), RPL4 (Co-fractionation; 4 records), RPL7 (Co-fractionation; 4 records), RPS6 (Co-fractionation; 4 records), ALG2 (Cross-Linking-MS (XL-MS); 3 records), DDX23 (Cross-Linking-MS (XL-MS); 3 records), FAM50A (Cross-Linking-MS (XL-MS); 3 records), ILF3 (Affinity Capture-MS; 3 records), MYC (Affinity Capture-MS; 3 records), PARK2 (Affinity Capture-MS; 3 records), RPL10 (Co-fractionation; 3 records), RPL11 (Co-fractionation; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
RPL21	“form complex”	“60S cytosolic large ribosomal subunit”	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
60S ribosomal subunit, cytoplasmic	47	RPL27, RPL9, RPLP2, RPL17, RPL19, RPL5, RPL12, RPL13, RPL13A, RPL30, RPL35, RPL35A, RPL36, RPL6, RPL18, RPL23A, RPL28, RPL32, RPL37A, RPL38, RPL7, RPL8, RPL10A, RPL21, RPL23, RPL7A, RPLP0, RPL14, RPL27A, RPL29, RPL3, RPL37, RPL39, RPL15, RPL34, RPL36A, RPLP1, RPL10, RPL18A, RPL22, RPL24, RPL31, RPL4, RPL41, UBA52, RPL11, RPL26
TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle)	25	RSL24D1, MOV10, RPL11, RPL14, RPL15, RPL27, RPL28, RPL35A, RPL36, RPL12, RPL13, RPL19, RPL7A, EIF6, RPL18A, RPL21, RPL32, RPL34, RPLP2, DICER1, RPL10A, RPL30, RPL37A, RPL7, RPLP1

Disease & clinical

Genetic variants

Variant evidence for RPL21: 36 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	12
Likely benign	10
Benign	13

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
139638	NM_000982.4(RPL21):c.95G>A (p.Arg32Gln)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore RPL21’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 475):

Position(s)	Effect	Δscore	Sites
13:27253756	acceptor_gain	1.0000
13:27253844–27253845	donor_loss	1.0000	5
13:27255351	donor_gain	1.0000
13:27256182–27256183	acceptor_loss	1.0000	6
13:27256335–27256336	donor_loss	1.0000	5
13:27253763–27253764	acceptor_loss	0.9900	6
13:27255240–27255241	acceptor_loss	0.9900	6
13:27255355–27255356	donor_loss	0.9900	6
13:27256432	acceptor_gain	0.9900
13:27256434–27256435	acceptor_loss	0.9900	6

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	9.17e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000116
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000167
Glioblastoma Multiforme (validation)	favorable	0.000418

Disease associations

OMIM: gene MIM:603636 | disease phenotypes: MIM:615885

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypotrichosis 12	Strong	Autosomal dominant	3
hypotrichosis simplex	Supportive	Autosomal dominant

Mondo (2): hypotrichosis 12 (MONDO:0014384), hypotrichosis simplex (MONDO:0018914)

Orphanet (1): Hypotrichosis simplex (Orphanet:55654)

HPO phenotypes

18 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000164	Abnormality of the dentition
HP:0000653	Sparse eyelashes
HP:0000951	Abnormality of the skin
HP:0000971	Abnormal sweat gland morphology
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology
HP:0002209	Sparse scalp hair
HP:0002215	Sparse axillary hair
HP:0002217	Slow-growing hair
HP:0002225	Sparse pubic hair
HP:0002231	Sparse body hair
HP:0003593	Infantile onset
HP:0008070	Sparse hair
HP:0011359	Dry hair
HP:0045075	Sparse eyebrow
HP:0100840	Aplasia/Hypoplasia of the eyebrow
HP:0200102	Sparse or absent eyelashes

GWAS associations

3 associations:

Study	Trait	p-value
GCST90011899_7	Aspartate aminotransferase levels	7e-9
GCST008747_87	Estimated glomerular filtration rate	7e-7
GCST000111_1	Electrocardiographic traits	8e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0004682	QT interval
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C537160	Hypotrichosis simplex *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066895 (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
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
5.78	Kd	1643	nM	CHEMBL3752910
5.78	ED50	1643	nM	CHEMBL3752910
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
5.00	Kd	9953	nM	CHEMBL5653589
5.00	ED50	9953	nM	CHEMBL5653589

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
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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149251: Binding affinity to human RPL21 incubated for 45 mins by Kinobead based pull down assay	kd	1.6429	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149251: Binding affinity to human RPL21 incubated for 45 mins by Kinobead based pull down assay	kd	9.9532	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, affects expression	5
sodium arsenite	increases abundance, increases expression, decreases expression, increases activity	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
4-hydroxy-equilenin	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	affects expression	1
calfactant	decreases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases 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.

1 trials:

NCT	Phase	Status	Title
NCT03492866	Phase 2	UNKNOWN	Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RPL21 across ~30M SureChEMBL compounds — explore on Sugi Predict.