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MRPL21

gene
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Also known as bL21m

Summary

MRPL21 (mitochondrial ribosomal protein L21, HGNC:14479) is a protein-coding gene on chromosome 11q13.3, encoding Large ribosomal subunit protein bL21m (Q7Z2W9). It is a selective cancer dependency (DepMap: 83.7% of cell lines).

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD).

Source: NCBI Gene 219927 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 43 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 83.7% of screened cell lines
  • MANE Select transcript: NM_181514

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:14479
Approved symbolMRPL21
Namemitochondrial ribosomal protein L21
Location11q13.3
Locus typegene with protein product
StatusApproved
AliasesbL21m
Ensembl geneENSG00000197345
Ensembl biotypeprotein_coding
OMIM611834
Entrez219927

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000362034, ENST00000450904, ENST00000536637, ENST00000541265, ENST00000541279, ENST00000544567, ENST00000565125, ENST00000567045, ENST00000918367, ENST00000918368

RefSeq mRNA: 2 — MANE Select: NM_181514 NM_181514, NM_181515

CCDS: CCDS44662, CCDS8186

Canonical transcript exons

ENST00000362034 — 7 exons

ExonStartEnd
ENSE000022909046890372368903832
ENSE000034678846889340368893455
ENSE000035630146889289068892993
ENSE000036231146889651568896678
ENSE000036256496890054868900605
ENSE000036537866889792768898012
ENSE000038419966889127868891395

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.9932 / max 480.7127, expressed in 1790 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
12102133.53051787
1210200.4627241

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
left ventricle myocardiumUBERON:000656697.51gold quality
mucosa of transverse colonUBERON:000499196.94gold quality
apex of heartUBERON:000209896.88gold quality
heart left ventricleUBERON:000208496.85gold quality
cardiac ventricleUBERON:000208296.67gold quality
right atrium auricular regionUBERON:000663196.64gold quality
gastrocnemiusUBERON:000138896.47gold quality
muscle of legUBERON:000138396.46gold quality
cardiac atriumUBERON:000208196.37gold quality
hindlimb stylopod muscleUBERON:000425296.30gold quality
heartUBERON:000094896.22gold quality
olfactory segment of nasal mucosaUBERON:000538696.07gold quality
muscle layer of sigmoid colonUBERON:003580596.04gold quality
anterior cingulate cortexUBERON:000983595.91gold quality
prefrontal cortexUBERON:000045195.89gold quality
transverse colonUBERON:000115795.80gold quality
kidney epitheliumUBERON:000481995.65gold quality
metanephros cortexUBERON:001053395.62gold quality
tibialis anteriorUBERON:000138595.58gold quality
myocardiumUBERON:000234995.50gold quality
hypothalamusUBERON:000189895.43gold quality
Brodmann (1909) area 9UBERON:001354095.41gold quality
popliteal arteryUBERON:000225095.34gold quality
tibial arteryUBERON:000761095.34gold quality
lower esophagusUBERON:001347395.34gold quality
lower esophagus muscularis layerUBERON:003583395.34gold quality
esophagogastric junction muscularis propriaUBERON:003584195.33gold quality
right coronary arteryUBERON:000162595.20gold quality
right frontal lobeUBERON:000281095.20gold quality
minor salivary glandUBERON:000183095.11gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes9.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TEAD1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

  • High MRPL21 expression is associated with esophageal squamous cell carcinoma. (PMID:26406417)
  • MRPL21 promotes HCC proliferation through TP53 mutation-induced apoptotic resistance. (PMID:38181584)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriomrpl21ENSDARG00000003846
mus_musculusMrpl21ENSMUSG00000024829
rattus_norvegicusMrpl21ENSRNOG00000013845
drosophila_melanogastermRpL21FBGN0036853
caenorhabditis_elegansWBGENE00023422

Protein

Protein identifiers

Large ribosomal subunit protein bL21m — Q7Z2W9 (reviewed: Q7Z2W9)

Alternative names: 39S ribosomal protein L21, mitochondrial

All UniProt accessions (5): F5H3L0, F5H4R5, F5H7V8, H3BUY0, Q7Z2W9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the mitochondrial large ribosomal subunit (mt-LSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.

Subcellular location. Mitochondrion.

Similarity. Belongs to the bacterial ribosomal protein bL21 family.

Isoforms (2)

UniProt IDNamesCanonical?
Q7Z2W9-11yes
Q7Z2W9-22

RefSeq proteins (2): NP_852615, NP_852616 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001787Ribosomal_bL21Family
IPR028909bL21-likeFamily
IPR036164bL21-like_sfHomologous_superfamily

Pfam: PF00829

UniProt features (17 total): strand 10, turn 3, transit peptide 1, chain 1, splice variant 1, helix 1

Structure

Experimental structures (PDB)

86 structures, top 30 by resolution.

PDBMethodResolution (Å)
7OF0ELECTRON MICROSCOPY2.2
7QI4ELECTRON MICROSCOPY2.21
8RRIELECTRON MICROSCOPY2.4
8QU5ELECTRON MICROSCOPY2.42
9OLFELECTRON MICROSCOPY2.46
7OF7ELECTRON MICROSCOPY2.5
7PO4ELECTRON MICROSCOPY2.56
6ZM6ELECTRON MICROSCOPY2.59
7O9MELECTRON MICROSCOPY2.6
7OF6ELECTRON MICROSCOPY2.6
9CN3ELECTRON MICROSCOPY2.62
7QI5ELECTRON MICROSCOPY2.63
7OF2ELECTRON MICROSCOPY2.7
7OF3ELECTRON MICROSCOPY2.7
7OF4ELECTRON MICROSCOPY2.7
8QU1ELECTRON MICROSCOPY2.74
9PR4ELECTRON MICROSCOPY2.77
9PRAELECTRON MICROSCOPY2.83
8ANYELECTRON MICROSCOPY2.85
6ZM5ELECTRON MICROSCOPY2.89
7QH7ELECTRON MICROSCOPY2.89
7ODRELECTRON MICROSCOPY2.9
7OF5ELECTRON MICROSCOPY2.9
8K2AELECTRON MICROSCOPY2.9
8OITELECTRON MICROSCOPY2.9
9PGLELECTRON MICROSCOPY2.9
9PGFELECTRON MICROSCOPY2.93
6VMIELECTRON MICROSCOPY2.96
6VLZELECTRON MICROSCOPY2.97
7QI6ELECTRON MICROSCOPY2.98

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q7Z2W9-F185.740.74

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

IDPathway
R-HSA-5368286Mitochondrial translation initiation
R-HSA-5389840Mitochondrial translation elongation
R-HSA-5419276Mitochondrial translation termination
R-HSA-9937383Mitochondrial ribosome-associated quality control
R-HSA-392499Metabolism of proteins
R-HSA-5368287Mitochondrial translation
R-HSA-72766Translation

MSigDB gene sets: 106 (showing top): MODULE_151, GOBP_MITOCHONDRIAL_TRANSLATION, chr11q13, GOBP_TRANSLATION, GGAANCGGAANY_UNKNOWN, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, AAAGACA_MIR511, GOCC_MITOCHONDRIAL_ENVELOPE, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, MODULE_114, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (2): mitochondrial translation (GO:0032543), translation (GO:0006412)

GO Molecular Function (2): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial large ribosomal subunit (GO:0005762), cytoplasm (GO:0005737), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Mitochondrial translation4
Translation1
Metabolism of proteins1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
mitochondrion1
translation1
mitochondrial gene expression1
peptidyltransferase activity1
translational initiation1
translational elongation1
translational termination1
macromolecule biosynthetic process1
protein metabolic process1
protein biosynthetic process1
nucleic acid binding1
structural molecule activity1
ribosome1
cytoplasm1
intracellular membrane-bounded organelle1
organelle inner membrane1
mitochondrial membrane1
organellar large ribosomal subunit1
mitochondrial ribosome1
mitochondrial protein-containing complex1
intracellular anatomical structure1
cellular anatomical structure1
intracellular membraneless organelle1
protein-containing complex1

Protein interactions and networks

STRING

2961 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MRPL21MRPL11Q9Y3B7825
MRPL21MRPL13Q9BYD1723
MRPL21MRPL4Q9BYD3717
MRPL21MRPL16Q9NX20709
MRPL21MRPL17Q9NRX2704
MRPL21MRPS11P82912652
MRPL21MRPS10P82664647
MRPL21MRPL33O75394619
MRPL21MRPL9Q9BYD2595
MRPL21MRPL36Q9P0J6595
MRPL21MRPS14O60783594
MRPL21MRPS16Q9Y3D3572
MRPL21MRPL24Q96A35570
MRPL21MRPL12P52815560
MRPL21MRPL19P49406541

IntAct

96 interactions, top by confidence:

ABTypeScore
YBX1SSBpsi-mi:“MI:0914”(association)0.710
LIN28AIGF2BP3psi-mi:“MI:0914”(association)0.640
MRPS30GTPBP10psi-mi:“MI:0914”(association)0.640
NPKPNA6psi-mi:“MI:0914”(association)0.550
RPS6IPO7psi-mi:“MI:0914”(association)0.530
MRPL50GTPBP10psi-mi:“MI:0914”(association)0.530
MRPL42GATCpsi-mi:“MI:0914”(association)0.530
CASQ2PES1psi-mi:“MI:0914”(association)0.530
MRPL13GTPBP10psi-mi:“MI:0914”(association)0.530
MRPL18GTPBP10psi-mi:“MI:0914”(association)0.530
MRPL2GTPBP10psi-mi:“MI:0914”(association)0.530
MRPL27MRPL33psi-mi:“MI:0914”(association)0.530
NDUFAB1MIEF1psi-mi:“MI:0915”(physical association)0.490
MRPL21TSC2psi-mi:“MI:0915”(physical association)0.370
Brwd3WDR91psi-mi:“MI:0914”(association)0.350
MRPL50MRPL43psi-mi:“MI:0914”(association)0.350
MRPL9MRPL43psi-mi:“MI:0914”(association)0.350
MRPL1MRPL43psi-mi:“MI:0914”(association)0.350
FOXL2RTCApsi-mi:“MI:0914”(association)0.350
NPHNRNPDLpsi-mi:“MI:0914”(association)0.350
NPKPNA6psi-mi:“MI:0914”(association)0.350
psi-mi:“MI:0914”(association)0.350
CUL3PXDNLpsi-mi:“MI:0914”(association)0.350
LRRK2psi-mi:“MI:0914”(association)0.350

BioGRID (231): MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS), MRPL21 (Affinity Capture-MS)

ESM2 similar proteins: A6QPQ5, A9X1A9, O95707, P0C2C1, P82664, P82670, P82675, P82915, P82919, P82933, Q08BI9, Q0P5E7, Q0VFH6, Q2KIB9, Q2KID9, Q2KIJ6, Q2TBK2, Q2TBR2, Q3MHY7, Q3SYS0, Q3T040, Q58DQ5, Q58DV5, Q5C9Z4, Q5R7B0, Q5REJ1, Q5REY4, Q5RFM3, Q641X9, Q7Z2W9, Q7Z7H8, Q8N3Z3, Q8TCC3, Q924T2, Q99N85, Q99N87, Q99N94, Q9BSH4, Q9BYD2, Q9BYD6

Diamond homologs: A4XYL4, A9FG66, A9H0E5, B5YEQ3, B6IR01, B8E0B4, B8FM66, C1DEA6, C4LJU6, Q0VSE8, Q2GGS5, Q2TBS2, Q3YRY0, Q54IF0, Q5FH96, Q5FUL4, Q5HB47, Q7SGE5, Q7Z2W9, Q8L9A0, Q9D1N9, P40858, Q9P7D4, B3Q725, Q07U69, Q0AWJ0, Q21D08, Q2J3K3, Q6NDF0, Q7UFG2, A5FV27, A5N6J9, A6LLU6, A6UDV2, A9BHC0, B0S3Z1, B5ELU4, B7ICN4, B7J429, B9E018

SIGNOR signaling

1 interactions.

AEffectBMechanism
MRPL21“form complex”“39S mitochondrial large ribosomal subunit”binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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:

PathwayPartnersFoldFDR
Mitochondrial ribosome-associated quality control2648.4×4e-36
Mitochondrial translation initiation2446.1×5e-33
Mitochondrial translation elongation2446.1×5e-33
Mitochondrial translation2143.8×3e-28
Mitochondrial translation termination2439.9×2e-31
Translation2422.6×3e-25
Peptide chain elongation713.5×2e-05
Viral mRNA Translation713.5×2e-05

GO biological processes:

GO termPartnersFoldFDR
mitochondrial translation2551.7×2e-34
translation2024.5×3e-20
cytoplasmic translation817.6×3e-06
negative regulation of translation511.7×6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance30
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1050 predictions. Top by Δscore:

VariantEffectΔscore
11:68892990:CTTT:Cacceptor_gain1.0000
11:68896509:TCTCA:Tdonor_loss1.0000
11:68896510:CTCA:Cdonor_loss1.0000
11:68896512:CACCT:Cdonor_loss1.0000
11:68896679:C:CCacceptor_gain1.0000
11:68897921:TCTTA:Tdonor_loss1.0000
11:68897922:CTTAC:Cdonor_loss1.0000
11:68897923:TTACC:Tdonor_loss1.0000
11:68897924:TA:Tdonor_loss1.0000
11:68897926:C:CTdonor_loss1.0000
11:68898008:CATAT:Cacceptor_gain1.0000
11:68898010:TAT:Tacceptor_gain1.0000
11:68898010:TATC:Tacceptor_loss1.0000
11:68898011:ATCT:Aacceptor_loss1.0000
11:68898012:TCTG:Tacceptor_loss1.0000
11:68898013:C:CCacceptor_gain1.0000
11:68898013:C:CGacceptor_loss1.0000
11:68898014:T:Gacceptor_loss1.0000
11:68900546:AC:Adonor_gain1.0000
11:68900547:CC:Cdonor_gain1.0000
11:68903717:TCTCA:Tdonor_loss1.0000
11:68903718:CTCA:Cdonor_loss1.0000
11:68903719:TCA:Tdonor_loss1.0000
11:68903720:CA:Cdonor_loss1.0000
11:68903722:C:CTdonor_loss1.0000
11:68892992:TT:Tacceptor_gain0.9900
11:68892993:TC:Tacceptor_loss0.9900
11:68892994:C:CCacceptor_gain0.9900
11:68892994:C:Tacceptor_loss0.9900
11:68892995:T:Cacceptor_loss0.9900

AlphaMissense

1301 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:68896621:G:TA97D0.996
11:68892971:C:GA158P0.995
11:68896623:A:CF96L0.994
11:68896623:A:TF96L0.994
11:68896625:A:GF96L0.994
11:68891368:C:GR194P0.992
11:68891365:A:TI195K0.991
11:68891371:A:TL193H0.990
11:68892964:A:TV160D0.990
11:68892982:A:TV154D0.990
11:68893445:A:TV136D0.990
11:68892970:G:TA158D0.989
11:68896622:C:GA97P0.988
11:68893448:A:GL135P0.987
11:68891365:A:CI195R0.986
11:68891371:A:GL193P0.986
11:68893429:G:CF141L0.985
11:68893429:G:TF141L0.985
11:68893431:A:GF141L0.985
11:68896573:A:GL113P0.985
11:68896615:A:TV99E0.984
11:68891365:A:GI195T0.983
11:68892921:G:CF174L0.983
11:68892921:G:TF174L0.983
11:68892923:A:GF174L0.983
11:68893418:C:AG145V0.983
11:68893430:A:GF141S0.983
11:68896577:C:GD112H0.983
11:68896588:A:TV108E0.983
11:68893424:A:GL143P0.982

dbSNP variants (sampled 300 via entrez): RS1000309507 (11:68902222 G>A), RS1000560736 (11:68905739 CG>C), RS1001045547 (11:68903815 G>T), RS1001079290 (11:68904546 C>T), RS1001381233 (11:68898491 C>T), RS1001832246 (11:68895722 G>A), RS1001892713 (11:68905260 C>T), RS1001980595 (11:68900812 T>C), RS1002178241 (11:68895983 C>G), RS1002325358 (11:68905004 G>A), RS1002379616 (11:68899407 T>C), RS1002556835 (11:68904076 T>G), RS1002657770 (11:68898285 G>A), RS1003055970 (11:68902027 C>G), RS1003394993 (11:68896367 C>A)

Disease associations

OMIM: gene MIM:611834 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067164 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
5.23Kd5949nMCHEMBL3752910
5.23ED505949nMCHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149886: Binding affinity to human MRPL21 incubated for 45 mins by Kinobead based pull down assaykd5.9488uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arseniteaffects cotreatment, increases expression, increases abundance2
Benzo(a)pyrenedecreases expression, increases methylation2
triphenyl phosphateaffects expression1
lead acetateaffects cotreatment, increases expression1
nobiletindecreases expression, decreases reaction1
sodium arsenatedecreases expression, decreases reaction1
arseniteaffects binding, increases reaction1
manganese chlorideincreases abundance, increases expression, affects cotreatment1
CGP 52608increases reaction, affects binding1
bisphenol AFincreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic aciddecreases expression1
Acetaminophendecreases expression, affects cotreatment1
Arsenicaffects cotreatment, increases abundance, increases expression1
Ivermectindecreases expression1
Lipopolysaccharidesaffects cotreatment, decreases expression1
Manganeseincreases abundance, increases expression, affects cotreatment1
Ribonucleotidesaffects binding1
Smokedecreases expression1
Thiramdecreases expression1
Valproic Acidaffects expression1
Cyclosporineincreases expression1
Aflatoxin B1increases methylation1
Asbestos, Crocidoliteincreases expression1
Copper Sulfatedecreases expression, increases expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5652928BindingBinding affinity to human MRPL21 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 78

This page pulls from 78 datasets indexed by BioBTree:

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