MRPL21

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
• GTEx eGene: eQTL in 50 tissues, sQTL in 48 (q < 0.05)
• Cancer dependency (DepMap): dependent in 83.7% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.96 (unconstrained)
• MANE Select transcript: NM_181514
• Interaction hub: 2,459 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14479
Approved symbol	MRPL21
Name	mitochondrial ribosomal protein L21
Location	11q13.3
Locus type	gene with protein product
Status	Approved
Aliases	bL21m
Ensembl gene	ENSG00000197345
Ensembl biotype	protein_coding
OMIM	611834
Entrez	219927

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 28 nonsense_mediated_decay, 11 protein_coding, 1 retained_intron

MANE Select: ENST00000362034

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

ENST00000362034, ENST00000450904, ENST00000536637, ENST00000541265, ENST00000541279, ENST00000544567, ENST00000565125, ENST00000567045, ENST00000918367, ENST00000918368, ENST00000976719, ENST00000976720, ENST00000976721, ENST00000976722, ENST00000976723, ENST00001037128, ENST00001037129, ENST00001037130, ENST00001062026, ENST00001062027, ENST00001062028, ENST00001062032, ENST00001062034, ENST00001062035, ENST00001062036, ENST00001062038, ENST00001062040, ENST00001062041, ENST00001062048, ENST00001062049, ENST00001062050, ENST00001062051, ENST00001062054, ENST00001062055, ENST00001094720, ENST00001094721, ENST00001094722, ENST00001094723, ENST00001131099, ENST00001142661

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

CCDS: CCDS44662, CCDS8186

Canonical transcript exons

ENST00000362034 — 7 exons

Exon	Start	End
ENSE00002290904	68903723	68903832
ENSE00003467884	68893403	68893455
ENSE00003563014	68892890	68892993
ENSE00003623114	68896515	68896678
ENSE00003625649	68900548	68900605
ENSE00003653786	68897927	68898012
ENSE00003841996	68891278	68891395

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.

Highest expression (Bgee): ventricle myocardium, mucosa of transverse colon, apex of heart, heart left ventricle, cardiac ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MRPL21 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 50 tissues and its splicing (sQTL) in 48 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 98 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	3.8e-204	-0.79	11:68885764:C:T
Skin Sun Exposed Lower leg	eqtl	1.4e-194	-0.84	11:68903812:G:GCCGCCGCCATCTTC
Thyroid	eqtl	1.9e-181	-0.86	11:68903812:G:GCCGCCGCCATCTTC
Cells Cultured fibroblasts	eqtl	7.4e-179	-0.56	11:68885764:C:T
Nerve Tibial	eqtl	2.2e-164	-0.85	11:68903812:G:GCCGCCGCCATCTTC
Esophagus Mucosa	eqtl	1.3e-161	-0.80	11:68885764:C:T
Skin Not Sun Exposed Suprapubic	eqtl	4.4e-160	-0.85	11:68885764:C:T
Esophagus Muscularis	eqtl	8.7e-159	-0.86	11:68885764:C:T
Adipose Subcutaneous	eqtl	1.9e-153	-0.76	11:68885764:C:T
Artery Aorta	eqtl	8.4e-135	-0.88	11:68903812:G:GCCGCCGCCATCTTC
Colon Transverse	eqtl	9.1e-130	-0.83	11:68885764:C:T
Colon Sigmoid	eqtl	1.3e-118	-0.95	11:68885764:C:T
Whole Blood	eqtl	8.1e-117	-0.51	11:68885764:C:T
Lung	eqtl	1.0e-113	-0.57	11:68885764:C:T
Esophagus Gastroesophageal Junction	eqtl	5.3e-112	-0.94	11:68885764:C:T
Adipose Visceral Omentum	eqtl	5.2e-110	-0.67	11:68885764:C:T
Testis	eqtl	1.5e-104	-0.97	11:68885764:C:T
Cells EBV-transformed lymphocytes	eqtl	4.8e-103	-0.77	11:68885764:C:T
Breast Mammary Tissue	eqtl	3.5e-98	-0.68	11:68885764:C:T
Pituitary	eqtl	5.9e-95	-1.11	11:68885764:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
121021	33.5305	1787
121020	0.4627	241

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	97.51	gold quality
mucosa of transverse colon	UBERON:0004991	96.94	gold quality
apex of heart	UBERON:0002098	96.88	gold quality
heart left ventricle	UBERON:0002084	96.85	gold quality
cardiac ventricle	UBERON:0002082	96.67	gold quality
right atrium auricular region	UBERON:0006631	96.64	gold quality
gastrocnemius	UBERON:0001388	96.47	gold quality
muscle of leg	UBERON:0001383	96.46	gold quality
cardiac atrium	UBERON:0002081	96.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.30	gold quality
heart	UBERON:0000948	96.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.04	gold quality
anterior cingulate cortex	UBERON:0009835	95.91	gold quality
prefrontal cortex	UBERON:0000451	95.89	gold quality
transverse colon	UBERON:0001157	95.80	gold quality
kidney epithelium	UBERON:0004819	95.65	gold quality
metanephros cortex	UBERON:0010533	95.62	gold quality
tibialis anterior	UBERON:0001385	95.58	gold quality
myocardium	UBERON:0002349	95.50	gold quality
hypothalamus	UBERON:0001898	95.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.41	gold quality
popliteal artery	UBERON:0002250	95.34	gold quality
tibial artery	UBERON:0007610	95.34	gold quality
lower esophagus	UBERON:0013473	95.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.33	gold quality
right coronary artery	UBERON:0001625	95.20	gold quality
right frontal lobe	UBERON:0002810	95.20	gold quality
minor salivary gland	UBERON:0001830	95.11	gold quality
aorta	UBERON:0000947	95.00	gold quality
amygdala	UBERON:0001876	94.96	gold quality
body of uterus	UBERON:0009853	94.92	gold quality
left uterine tube	UBERON:0001303	94.90	gold quality
left coronary artery	UBERON:0001626	94.85	gold quality
right uterine tube	UBERON:0001302	94.79	gold quality
body of stomach	UBERON:0001161	94.78	gold quality
thoracic aorta	UBERON:0001515	94.72	gold quality
ascending aorta	UBERON:0001496	94.71	gold quality
descending thoracic aorta	UBERON:0002345	94.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.68	gold quality
endocervix	UBERON:0000458	94.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.61	gold quality
putamen	UBERON:0001874	94.57	gold quality
cerebellar cortex	UBERON:0002129	94.54	gold quality
cerebellar hemisphere	UBERON:0002245	94.54	gold quality
esophagus	UBERON:0001043	94.50	gold quality
left ovary	UBERON:0002119	94.48	gold quality
islet of Langerhans	UBERON:0000006	94.47	gold quality
colon	UBERON:0001155	94.44	gold quality
skin of abdomen	UBERON:0001416	94.44	gold quality
caudate nucleus	UBERON:0001873	94.43	gold quality
body of pancreas	UBERON:0001150	94.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.42	gold quality
skin of leg	UBERON:0001511	94.41	gold quality
right ovary	UBERON:0002118	94.41	gold quality
saliva-secreting gland	UBERON:0001044	94.40	gold quality
coronary artery	UBERON:0001621	94.38	gold quality
ectocervix	UBERON:0012249	94.37	gold quality
large intestine	UBERON:0000059	94.34	gold quality
nucleus accumbens	UBERON:0001882	94.34	gold quality
rectum	UBERON:0001052	94.28	gold quality
ileal mucosa	UBERON:0000331	94.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.09	gold quality
muscle tissue	UBERON:0002385	94.06	gold quality
adenohypophysis	UBERON:0002196	94.05	gold quality
right testis	UBERON:0004534	94.05	gold quality
left lobe of thyroid gland	UBERON:0001120	94.04	gold quality
left adrenal gland cortex	UBERON:0035825	94.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.96	gold quality
intestine	UBERON:0000160	93.95	gold quality
left testis	UBERON:0004533	93.92	gold quality
esophagus mucosa	UBERON:0002469	93.90	gold quality
skeletal muscle tissue	UBERON:0001134	93.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.87	gold quality
adult mammalian kidney	UBERON:0000082	93.84	gold quality
right adrenal gland cortex	UBERON:0035827	93.84	gold quality
cerebellum	UBERON:0002037	93.83	gold quality
lower esophagus mucosa	UBERON:0035834	93.76	gold quality
smooth muscle tissue	UBERON:0001135	93.75	gold quality
cortex of kidney	UBERON:0001225	93.70	gold quality
left adrenal gland	UBERON:0001234	93.70	gold quality
right lobe of liver	UBERON:0001114	93.68	gold quality
right adrenal gland	UBERON:0001233	93.61	gold quality
pancreas	UBERON:0001264	93.58	gold quality
upper arm skin	UBERON:0004263	93.58	silver quality
right lobe of thyroid gland	UBERON:0001119	93.55	gold quality
frontal cortex	UBERON:0001870	93.54	gold quality
substantia nigra	UBERON:0002038	93.53	gold quality
tibial nerve	UBERON:0001323	93.48	gold quality
thyroid gland	UBERON:0002046	93.47	gold quality
neocortex	UBERON:0001950	93.44	gold quality
mouth mucosa	UBERON:0003729	93.44	gold quality
ganglionic eminence	UBERON:0004023	93.43	gold quality
omental fat pad	UBERON:0010414	93.34	gold quality
peritoneum	UBERON:0002358	93.31	gold quality
mucosa of stomach	UBERON:0001199	93.25	gold quality
stomach	UBERON:0000945	93.23	gold quality
adrenal cortex	UBERON:0001235	93.17	gold quality
monocyte	CL:0000576	93.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.23

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	122.8	not detected
Tongue	tissue	101.6
Salivary gland	tissue	93.6	medium
Heart muscle	tissue	93.0	low
Bone marrow	tissue	57.0	low
Frontal cortex	tissue	54.1
Parathyroid gland	tissue	52.8	medium
Liver	tissue	50.9	not detected
Caudate putamen	tissue	50.1
Ovary	tissue	49.2	not detected
Breast	tissue	49.1	medium
Kidney	tissue	49.0	medium
Colon	tissue	46.6	medium
Epididymis	tissue	45.6	medium
Esophagus	tissue	45.5	medium
Pancreas	tissue	45.3	medium
Vagina	tissue	43.1	medium
Pituitary gland	tissue	42.7
Fallopian tube	tissue	42.5	medium
Thyroid gland	tissue	41.9	medium
Lymph node	tissue	41.0	medium
Urinary bladder	tissue	40.7	medium
Tonsil	tissue	40.2	medium
Rectum	tissue	39.8	medium
Small intestine	tissue	38.8	medium
Seminal vesicle	tissue	36.8	medium
Locus coeruleus	tissue	36.8
Duodenum	tissue	36.3	medium
Choroid plexus	tissue	35.7
Cervix	tissue	35.4	medium
Postcentral gyrus	tissue	34.9
Thymus	tissue	34.6
Skin 1	tissue	34.2	medium
Adrenal gland	tissue	33.3	medium
Prostate	tissue	33.0	low
Smooth muscle	tissue	32.7	medium
Appendix	tissue	32.0	medium
Stomach 1	tissue	31.3	medium
Placenta	tissue	31.0	medium
Nucleus accumbens	tissue	30.4
Adipose tissue	tissue	29.0	not detected
Hippocampus	tissue	28.8	not detected
Endometrium 1	tissue	28.7	not detected
Retina	tissue	27.5
Testis	tissue	25.6	medium
Gallbladder	tissue	25.4	medium
Lung	tissue	24.0	not detected
Spleen	tissue	22.8	medium
Thalamus	tissue	12.7
Superior colliculi	tissue	11.8
Pons	tissue	11.6
Cerebral cortex	tissue	11.5	low
Somatosensory cortex	tissue	11.5
Hippocampal formation	tissue	11.2
Midbrain	tissue	11.0
Motor cortex	tissue	10.5
Medulla oblongata	tissue	10.5
Occipital cortex	tissue	10.4
Putamen	tissue	10.3
Substantia nigra	tissue	10.2

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (60.3), Cerebellar nuclei (46.3), Lateral hypothalamic area (39.5), Spinal trigeminal nucleus, interpolar (39.5), Pontine raphe nucleus (39.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TEAD1

Functional genomics

gnomAD constraint: pLI 6.69e-05, LOEUF 0.964, missense Z 0.277 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000362034 — one region, missense o/e 0.99. DepMap (CRISPR cell-line fitness): dependent in 83.7% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SF-295 (-2.04), COR-L311 (-1.939), T.T (-1.844), OCI-AML2 (-1.806), SNU-398 (-1.801), SLR 20 (-1.789), U-937 (-1.763), NCI-H1437 (-1.752), SU-DHL-10 (-1.721), SNU-869 (-1.701), LN-428 (-1.671), ACC-MESO-1 (-1.638), JHH-4 (-1.632), NCI-H1581 (-1.616), SU-DHL-4 (-1.587).

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

Organism	Symbol	Gene ID
danio_rerio	mrpl21	ENSDARG00000003846
mus_musculus	Mrpl21	ENSMUSG00000024829
rattus_norvegicus	Mrpl21	ENSRNOG00000013845
drosophila_melanogaster	mRpL21	FBGN0036853
caenorhabditis_elegans		WBGENE00023422

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
Bos taurus	Q2TBS2	81.4%	Diamond
Neurospora crassa OR74A	Q7SGE5	39.3%	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
CPT1A	protein-coding	1374
IGHMBP2	protein-coding	3508
MRGPRF-AS1	ncRNA	101928200
MRGPRF	protein-coding	116535
LINC02701	ncRNA	105369364
TESMIN	protein-coding	9633
MRGPRD	protein-coding	116512

Protein

Protein identifiers

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

Alternative names: 39S ribosomal protein L21, mitochondrial

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

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 ID	Names	Canonical?
Q7Z2W9-1	1	yes
Q7Z2W9-2	2

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

Domains & families (InterPro)

ID	Name	Type
IPR001787	Ribosomal_bL21	Family
IPR028909	bL21-like	Family
IPR036164	bL21-like_sf	Homologous_superfamily

Pfam: PF00829

UniProt features (22 total): strand 10, helix 6, turn 3, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

showing 30 of 92 structures by resolution:

PDB	Title	Method	Resolution (Å)
7OF0	Structure of a human mitochondrial ribosome large subunit assembly intermediate in …	ELECTRON MICROSCOPY	2.2
7QI4	Human mitochondrial ribosome at 2.2 A resolution (bound to partly built tRNAs and mRNA)	ELECTRON MICROSCOPY	2.21
8RRI	Human mitochondrial ribosome in complex with antibiotic tigecycline	ELECTRON MICROSCOPY	2.4
8QU5	mt-LSU assembly intermediate in GTPBP8 knock-out cells, state 2	ELECTRON MICROSCOPY	2.42
9OLF	Membrane-associated human mitoribosome in complex with TACO1	ELECTRON MICROSCOPY	2.46
7OF7	Structure of a human mitochondrial ribosome large subunit assembly intermediate in …	ELECTRON MICROSCOPY	2.5
7PO4	Assembly intermediate of human mitochondrial ribosome large subunit (largely unfolded …	ELECTRON MICROSCOPY	2.56
6ZM6	Human mitochondrial ribosome in complex with mRNA, A/A tRNA and P/P tRNA	ELECTRON MICROSCOPY	2.59
7O9M	Human mitochondrial ribosome large subunit assembly intermediate with MTERF4-NSUN4, MRM2 …	ELECTRON MICROSCOPY	2.6
7OF6	Structure of mature human mitochondrial ribosome large subunit in complex with GTPBP6 …	ELECTRON MICROSCOPY	2.6
9CN3	Human 39S mitoribosome in complex with antibiotic Linezolid	ELECTRON MICROSCOPY	2.62
7QI5	Human mitochondrial ribosome in complex with mRNA, A/A-, P/P- and E/E-tRNAs at 2.63 A …	ELECTRON MICROSCOPY	2.63
9RU6	Human mitoribosome bound to TACO1 (Translational activator of COX1), mRNA, A/A-, P/P- and …	ELECTRON MICROSCOPY	2.64
7OF2	Structure of a human mitochondrial ribosome large subunit assembly intermediate in …	ELECTRON MICROSCOPY	2.7
7OF3	Structure of a human mitochondrial ribosome large subunit assembly intermediate in …	ELECTRON MICROSCOPY	2.7
7OF4	Structure of mature human mitochondrial ribosome large subunit in complex with GTPBP6 …	ELECTRON MICROSCOPY	2.7
8QU1	mt-LSU assembly intermediate in GTPBP8 knock-out cells, state 1	ELECTRON MICROSCOPY	2.74
9PR4	In Situ Structure of the Human Mitochondrial Large Subunit 39S in Complex with TACO1	ELECTRON MICROSCOPY	2.77
9PRA	In Situ Structure of the Human Mitoribosome Large Subunit 39S in Complex with EF-Tu	ELECTRON MICROSCOPY	2.83
8ANY	Human mitochondrial ribosome in complex with LRPPRC, SLIRP, A-site, P-site, E-site tRNAs …	ELECTRON MICROSCOPY	2.85
6ZM5	Human mitochondrial ribosome in complex with OXA1L, mRNA, A/A tRNA, P/P tRNA and nascent …	ELECTRON MICROSCOPY	2.89
7QH7	Cryo-EM structure of the human mtLSU assembly intermediate upon MRM2 depletion - class 4	ELECTRON MICROSCOPY	2.89
7ODR	State A of the human mitoribosomal large subunit assembly intermediate	ELECTRON MICROSCOPY	2.9
7OF5	Structure of a human mitochondrial ribosome large subunit assembly intermediate in …	ELECTRON MICROSCOPY	2.9
8K2A	Cryo-EM structure of the human 55S mitoribosome with Tigecycline	ELECTRON MICROSCOPY	2.9
8OIT	39S human mitochondrial large ribosomal subunit with mtRF1 and P-site tRNA	ELECTRON MICROSCOPY	2.9
9PGL	In situ structure of the human mitoribosome in the A-P state with TACO1	ELECTRON MICROSCOPY	2.9
9VXM	Human mitoribosome in a non-rotated state, with multiple neomycin molecules bound …	ELECTRON MICROSCOPY	2.9
9PGF	In situ structure of the human mitoribosome in the P state	ELECTRON MICROSCOPY	2.93
6VMI	Structure of the human mitochondrial ribosome-EF-G1 complex (ClassIII)	ELECTRON MICROSCOPY	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z2W9-F1	85.74	0.74

Human Protein Atlas

Protein class: Ribosomal proteins, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-9937383	Mitochondrial ribosome-associated quality control	curated
R-HSA-5419276	Mitochondrial translation termination	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-5368287	Mitochondrial translation	—
R-HSA-5389840	Mitochondrial translation elongation	electronic
R-HSA-5368286	Mitochondrial translation initiation	electronic
R-HSA-72766	Translation	—

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

3 top-level categories:

Category	Pathways
Mitochondrial translation	4
Translation	1
Metabolism of proteins	1

GO top-level categories

24 GO namespaces:

Category	Terms
mitochondrion	1
translation	1
mitochondrial gene expression	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
structural molecule activity	1
ribosome	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organellar large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrial large ribosomal subunit	CC	direct assay
mitochondrion	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 2,459 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL21	MRPL11	Q9Y3B7	689
MRPL21	MRPL16	Q9NX20	667
MRPL21	MRPL17	Q9NRX2	549
MRPL21	MRPL36	Q9P0J6	549
MRPL21	MRPS11	P82912	542
MRPL21	MRPL33	O75394	528
MRPL21	MRPL24	Q96A35	526
MRPL21	MRPL9	Q9BYD2	522
MRPL21	MRPL13	Q9BYD1	520
MRPL21	MRPS10	P82664	506
MRPL21	MRPL3	P09001	497
MRPL21	MRPS14	O60783	492
MRPL21	MRPL12	P52815	490
MRPL21	MRPS16	Q9Y3D3	477
MRPL21	MRPL1	Q9BYD6	454

IntAct

Human interaction partners of MRPL21 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
TSC2	physical association	0.370	1
FDXR	association	0.350	1
GTPBP6	association	0.350	1
RPL3	association	0.350	1

BioGRID (234 interactions; top human partners by supporting records): MRPL4 (Affinity Capture-MS; 4 records), MRPL50 (Affinity Capture-MS; 4 records), MRPS30 (Affinity Capture-MS; 4 records), AUH (Affinity Capture-MS; 3 records), GRSF1 (Proximity Label-MS; 3 records), MRPL30 (Affinity Capture-MS; 3 records), MRPL39 (Affinity Capture-MS; 3 records), MRPL44 (Affinity Capture-MS; 3 records), MRPL47 (Affinity Capture-MS; 3 records), MTIF2 (Affinity Capture-MS; 3 records), C1QBP (Proximity Label-MS; 2 records), C6orf203 (Affinity Capture-MS; 2 records), CASQ2 (Affinity Capture-MS; 2 records), CLPP (Proximity Label-MS; 2 records), CS (Proximity Label-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
MRPL21	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Protein complexes (CORUM) (2)

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

2 complexes by size:

Complex	Subunits	Members
55S ribosome, mitochondrial	78	MRPS30, MRPL1, MRPL14, MRPL41, MRPL45, MRPL50, MRPL54, MRPS18B, MRPS2, MRPS21, MRPS34, MRPL17, MRPS6, MRPS17, MRPS31, MRPS33, MRPL21, MRPL24, MRPS10, MRPS11, MRPL12, MRPL22, MRPL47, MRPL49, MRPS35, MRPS7, MRPL28, MRPL37, MRPL40, MRPL48, MRPS18A, MRPS22, MRPS23, MRPL13, MRPL46, MRPS28, MRPL16, MRPL23, MRPL39, MRPL52, MRPL53, MRPL19, MRPL42, MRPL44, MRPL11, MRPL2, MRPL27, MRPL33, MRPL34, MRPL35, MRPS25, MRPS26, DAP3, MRPL18, MRPL38, MRPL9, MRPS12, MRPS27, MRPS5, MRPS9, MRPL20, MRPL30, MRPL36, MRPL43, MRPS14, KGD4, MRPL32, MRPL4, MRPL51, MRPS15, MRPS16, MRPL3, MRPL55, MRPS18C, LACTB, MRPL10, MRPL15, MRPS24
39S ribosomal subunit, mitochondrial	48	LACTB, MRPL1, MRPL15, MRPL18, MRPL2, MRPL35, MRPL37, MRPL51, MRPL16, MRPL19, MRPL54, MRPL24, MRPL27, MRPL30, MRPL32, MRPL34, MRPL36, MRPL38, MRPL42, MRPL12, MRPL21, MRPL28, MRPL44, MRPL45, MRPL9, MRPL17, MRPL43, MRPL49, MRPL50, MRPL13, MRPL20, MRPL4, MRPL41, MRPL46, MRPL47, MRPL48, MRPL52, MRPL10, MRPL14, MRPL23, MRPL39, MRPL40, MRPL53, MRPL55, MRPL11, MRPL22, MRPL3, MRPL33

Disease & clinical

Genetic variants

Variant evidence for MRPL21: 43 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 594):

Position(s)	Effect	Δscore	Sites
11:68896513–68896514	donor_loss	1.0000	5
11:68897925–68897926	donor_loss	1.0000	5
11:68898013–68898014	acceptor_loss	1.0000	5
11:68903721–68903722	donor_loss	1.0000	5
11:68892994–68892995	acceptor_loss	0.9900	6
11:68896679–68896680	acceptor_loss	0.9900	6
11:68898013	acceptor_loss	0.9900
11:68893317	donor_gain	0.9800
11:68896513	donor_loss	0.9800
11:68893417	donor_gain	0.9700

AlphaMissense

327 missense substitutions predicted likely pathogenic (of 1,301 scored), across 90 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
D112	8	0.959	0.983
F96	8	0.928	0.994
F141	8	0.897	0.985
W106	7	0.926	0.954
F174	7	0.895	0.983
E162	7	0.833	0.974
Q105	7	0.814	0.964
G145	6	0.939	0.983
P147	6	0.916	0.960
K132	6	0.903	0.920
K107	6	0.878	0.975
I195	6	0.862	0.991
V108	6	0.861	0.983
V98	6	0.760	0.974
V83	6	0.748	0.934
V99	6	0.733	0.984
G137	5	0.944	0.969
V156	5	0.881	0.981
V133	5	0.879	0.976
G125	5	0.862	0.966

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
Lung Adenocarcinoma (validation)	unfavorable	9.88e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000132
Lung Adenocarcinoma (TCGA)	unfavorable	0.000198
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000824

Disease associations

OMIM: gene MIM:611834 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067164 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.23	Kd	5949	nM	CHEMBL3752910
5.23	ED50	5949	nM	CHEMBL3752910

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.

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	2149886: Binding affinity to human MRPL21 incubated for 45 mins by Kinobead based pull down assay	kd	5.9488	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, increases expression	1
nobiletin	decreases reaction, decreases expression	1
sodium arsenate	decreases expression, decreases reaction	1
arsenite	increases reaction, affects binding	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
CGP 52608	affects binding, increases reaction	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	increases expression	1
Copper Sulfate	decreases expression, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652928	Binding	Binding affinity to human MRPL21 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MRPL21 across ~30M SureChEMBL compounds — explore on Sugi Predict.