MRPL51

Summary

MRPL51 (mitochondrial ribosomal protein L51, HGNC:14044) is a protein-coding gene on chromosome 12p13.31, encoding Large ribosomal subunit protein mL51 (Q4U2R6). It is a selective cancer dependency (DepMap: 29.3% 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. Pseudogenes corresponding to this gene are found on chromosomes 4p and 21q.

Source: NCBI Gene 51258 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total
• Cancer dependency (DepMap): dependent in 29.3% of screened cell lines
• MANE Select transcript: NM_016497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14044
Approved symbol	MRPL51
Name	mitochondrial ribosomal protein L51
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CDA09, HSPC241, bMRP64, mL51
Ensembl gene	ENSG00000111639
Ensembl biotype	protein_coding
OMIM	611855
Entrez	51258

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000229238, ENST00000537701, ENST00000538814, ENST00000540949, ENST00000543164, ENST00000543703, ENST00000543959, ENST00000925507

RefSeq mRNA: 1 — MANE Select: NM_016497 NM_016497

CCDS: CCDS8547

Canonical transcript exons

ENST00000229238 — 3 exons

Exon	Start	End
ENSE00000866916	6493058	6493262
ENSE00002315871	6491886	6492467
ENSE00003679423	6492862	6492972

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 112.9786 / max 1861.4228, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129103	98.9481	1824
129105	11.8481	1780
129104	2.1825	1297

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.31	gold quality
kidney epithelium	UBERON:0004819	99.30	gold quality
right testis	UBERON:0004534	99.26	gold quality
left testis	UBERON:0004533	99.25	gold quality
upper arm skin	UBERON:0004263	99.15	gold quality
ileal mucosa	UBERON:0000331	99.11	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.06	gold quality
tibialis anterior	UBERON:0001385	98.93	gold quality
myocardium	UBERON:0002349	98.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.64	gold quality
quadriceps femoris	UBERON:0001377	98.55	gold quality
heart left ventricle	UBERON:0002084	98.55	gold quality
cardiac ventricle	UBERON:0002082	98.54	gold quality
vastus lateralis	UBERON:0001379	98.51	gold quality
deltoid	UBERON:0001476	98.47	gold quality
islet of Langerhans	UBERON:0000006	98.42	gold quality
testis	UBERON:0000473	98.42	gold quality
apex of heart	UBERON:0002098	98.41	gold quality
adult organism	UBERON:0007023	98.40	gold quality
cardiac atrium	UBERON:0002081	98.38	gold quality
heart	UBERON:0000948	98.36	gold quality
right atrium auricular region	UBERON:0006631	98.36	gold quality
gastrocnemius	UBERON:0001388	98.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.31	gold quality
skeletal muscle organ	UBERON:0014892	98.30	gold quality
muscle of leg	UBERON:0001383	98.28	gold quality
heart right ventricle	UBERON:0002080	98.27	gold quality
muscle tissue	UBERON:0002385	98.26	gold quality
mucosa of transverse colon	UBERON:0004991	98.26	gold quality
skeletal muscle tissue	UBERON:0001134	98.24	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	33.22
E-CURD-122	yes	16.22
E-GEOD-81383	no	531.69
E-GEOD-110499	no	446.19
E-MTAB-7037	no	439.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting MRPL51, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-4323	93.93	63.89	656

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.3% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrpl51	ENSDARG00000041340
mus_musculus	Mrpl51	ENSMUSG00000030335
rattus_norvegicus	Mrpl51	ENSRNOG00000019165
drosophila_melanogaster	mRpL51	FBGN0032053
caenorhabditis_elegans		WBGENE00011740

Protein

Protein identifiers

Large ribosomal subunit protein mL51 — Q4U2R6 (reviewed: Q4U2R6)

Alternative names: 39S ribosomal protein L51, mitochondrial, bMRP-64

All UniProt accessions (4): Q4U2R6, A0A087WU28, A0A0B4J2C1, M0R176

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. Interacts with OXA1L.

Subcellular location. Mitochondrion.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mL51 family.

RefSeq proteins (1): NP_057581* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019373	Ribosomal_mL51	Family

Pfam: PF10244

UniProt features (13 total): helix 7, turn 2, transit peptide 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7OF0	ELECTRON MICROSCOPY	2.2
7QI4	ELECTRON MICROSCOPY	2.21
8RRI	ELECTRON MICROSCOPY	2.4
8QU5	ELECTRON MICROSCOPY	2.42
9OLF	ELECTRON MICROSCOPY	2.46
7OF7	ELECTRON MICROSCOPY	2.5
7PO4	ELECTRON MICROSCOPY	2.56
6ZM6	ELECTRON MICROSCOPY	2.59
7O9M	ELECTRON MICROSCOPY	2.6
7OF6	ELECTRON MICROSCOPY	2.6
9CN3	ELECTRON MICROSCOPY	2.62
7QI5	ELECTRON MICROSCOPY	2.63
7OF2	ELECTRON MICROSCOPY	2.7
7OF3	ELECTRON MICROSCOPY	2.7
7OF4	ELECTRON MICROSCOPY	2.7
9PR4	ELECTRON MICROSCOPY	2.77
9PRA	ELECTRON MICROSCOPY	2.83
8ANY	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
7QH7	ELECTRON MICROSCOPY	2.89
7ODR	ELECTRON MICROSCOPY	2.9
7OF5	ELECTRON MICROSCOPY	2.9
8K2A	ELECTRON MICROSCOPY	2.9
8OIT	ELECTRON MICROSCOPY	2.9
9PGL	ELECTRON MICROSCOPY	2.9
9PGF	ELECTRON MICROSCOPY	2.93
6VMI	ELECTRON MICROSCOPY	2.96
6VLZ	ELECTRON MICROSCOPY	2.97
7QI6	ELECTRON MICROSCOPY	2.98
9PSM	ELECTRON MICROSCOPY	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4U2R6-F1	86.80	0.71

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

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

MSigDB gene sets: 152 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, ACEVEDO_LIVER_CANCER_UP, BURTON_ADIPOGENESIS_6, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, GCCATNTTG_YY1_Q6, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE, MARSON_BOUND_BY_E2F4_UNSTIMULATED

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

GO Molecular Function (2): structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial ribosome (GO:0005761), mitochondrial large ribosomal subunit (GO:0005762), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial translation	4
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL51	MRPL48	Q96GC5	710
MRPL51	MRPL49	Q13405	692
MRPL51	MRPL20	Q9BYC9	689
MRPL51	MRPS21	P82921	625
MRPL51	MRPS25	P82663	624
MRPL51	MRPL55	Q7Z7F7	614
MRPL51	NDUFA1	O15239	591
MRPL51	MRPS14	O60783	525
MRPL51	MRPS18C	Q9Y3D5	522
MRPL51	MRPL50	Q8N5N7	510
MRPL51	ZSWIM7	Q19AV6	493
MRPL51	MRPS30	Q9NP92	493
MRPL51	PPP4R3B	Q5MIZ7	490
MRPL51	COA5	Q86WW8	479
MRPL51	GCSH	P23434	474

IntAct

90 interactions, top by confidence:

A	B	Type	Score
MRPL37	HSPD1	psi-mi:“MI:0914”(association)	0.710
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
MRPL10	ZZEF1	psi-mi:“MI:0914”(association)	0.530
MRPL42	GATC	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	psi-mi:“MI:0914”(association)	0.530
MRPL41	MRPL3	psi-mi:“MI:0914”(association)	0.530
MRPL13	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
MRPL50	MRPL43	psi-mi:“MI:0914”(association)	0.350
MRPL9	MRPL43	psi-mi:“MI:0914”(association)	0.350
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
HIF1AN	ARID1A	psi-mi:“MI:0914”(association)	0.350
ALYREF		psi-mi:“MI:0914”(association)	0.350
MRPL4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
MRPL12		psi-mi:“MI:0914”(association)	0.350
RPS8	RRP8	psi-mi:“MI:0914”(association)	0.350
MRPL39	PTCD1	psi-mi:“MI:0914”(association)	0.350
MRPL47	MRPL33	psi-mi:“MI:0914”(association)	0.350
ATAD3A	TMEM223	psi-mi:“MI:0914”(association)	0.350
PSME3	C11orf98	psi-mi:“MI:0914”(association)	0.350
rl36a_rl36l_human	IPO5	psi-mi:“MI:0914”(association)	0.350
H1-7		psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (189): MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Co-fractionation), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS), MRPL51 (Affinity Capture-MS)

ESM2 similar proteins: A1TYV1, A3M7E7, A4SHF6, A7HUX6, A7IDK1, A8IM57, A9HHS1, A9L948, B0VBX6, B0VUE9, B1VFG4, B2HVM2, B2ICM8, B4RYA0, B6INQ0, B7GZ34, B7I4A2, B8EK30, B8H4M5, C1D0Z8, G2TRQ8, O14187, P00129, P16135, P90993, Q02950, Q15N51, Q1GDB7, Q22438, Q28GD1, Q29PG4, Q2G8J9, Q2RVH2, Q4U2R6, Q5BJJ8, Q5FNB8, Q5ZKG1, Q61SE7, Q66KZ3, Q6CAD1

Diamond homologs: P0C2B6, Q28GD1, Q29PG4, Q4U2R6, Q5BJJ8, Q5ZKG1, Q66KZ3, Q9CPY1, Q9VLJ9, Q22438, Q61SE7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL51	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial ribosome-associated quality control	25	48.7×	6e-35
Mitochondrial translation initiation	23	46.3×	9e-32
Mitochondrial translation elongation	23	46.3×	9e-32
Mitochondrial translation	21	45.9×	6e-29
Mitochondrial translation termination	23	40.1×	3e-30
Translation	22	21.7×	9e-23
Regulation of expression of SLITs and ROBOs	6	6.6×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	25	52.3×	1e-34
translation	18	22.3×	2e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

421 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6492857:CTTA:C	donor_loss	1.0000
12:6492858:TTAC:T	donor_loss	1.0000
12:6492859:TA:T	donor_loss	1.0000
12:6492860:A:AC	donor_gain	1.0000
12:6492860:A:AG	donor_loss	1.0000
12:6492860:AC:A	donor_gain	1.0000
12:6492861:C:CC	donor_gain	1.0000
12:6492861:CC:C	donor_gain	1.0000
12:6492970:CAC:C	acceptor_gain	1.0000
12:6492971:ACC:A	acceptor_loss	1.0000
12:6492973:C:CA	acceptor_loss	1.0000
12:6492974:T:G	acceptor_loss	1.0000
12:6493362:T:TA	donor_gain	1.0000
12:6492468:C:CA	acceptor_loss	0.9900
12:6492468:C:CC	acceptor_gain	0.9900
12:6492469:T:G	acceptor_loss	0.9900
12:6492470:G:GC	acceptor_gain	0.9900
12:6492968:CACAC:C	acceptor_gain	0.9900
12:6492969:ACAC:A	acceptor_gain	0.9900
12:6492970:CACC:C	acceptor_gain	0.9900
12:6492973:C:CC	acceptor_gain	0.9900
12:6492979:A:AC	acceptor_gain	0.9900
12:6493343:C:A	donor_gain	0.9900
12:6493347:T:TA	donor_gain	0.9900
12:6493348:C:A	donor_gain	0.9900
12:6493463:T:A	donor_gain	0.9900
12:6493826:G:GT	donor_gain	0.9900
12:6492463:GTTTC:G	acceptor_gain	0.9800
12:6492464:TTTC:T	acceptor_gain	0.9800
12:6492465:TTC:T	acceptor_gain	0.9800

AlphaMissense

839 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6492423:A:G	W79R	0.993
12:6492423:A:T	W79R	0.993
12:6492389:C:G	R90P	0.992
12:6492376:C:A	K94N	0.989
12:6492376:C:G	K94N	0.989
12:6492913:A:G	W47R	0.989
12:6492913:A:T	W47R	0.989
12:6492380:C:G	R93P	0.988
12:6492867:A:G	I62T	0.987
12:6492879:T:A	D58V	0.984
12:6492890:G:C	F54L	0.983
12:6492890:G:T	F54L	0.983
12:6492892:A:G	F54L	0.983
12:6492878:G:C	D58E	0.981
12:6492878:G:T	D58E	0.981
12:6492879:T:G	D58A	0.981
12:6492888:C:T	G55E	0.981
12:6492290:C:G	R123P	0.980
12:6492395:A:G	L88S	0.980
12:6492411:A:G	W83R	0.980
12:6492411:A:T	W83R	0.980
12:6492911:C:A	W47C	0.980
12:6492911:C:G	W47C	0.980
12:6492419:A:T	L80H	0.979
12:6492320:C:G	R113P	0.976
12:6492421:C:A	W79C	0.976
12:6492421:C:G	W79C	0.976
12:6492329:A:G	L110P	0.975
12:6492419:A:G	L80P	0.975
12:6492467:C:A	G64V	0.975

dbSNP variants (sampled 300 via entrez): RS1001090844 (12:6491647 C>G), RS1001125 (12:6492808 T>C), RS1001126 (12:6492736 A>G), RS1001127 (12:6492577 A>C,T), RS1001266777 (12:6493647 G>A,T), RS1001297938 (12:6493411 C>A,T), RS1002324800 (12:6492466 T>A,G), RS1002986437 (12:6494756 G>A,C,T), RS1003331385 (12:6493622 C>T), RS1003614727 (12:6494735 T>A), RS1003645862 (12:6494423 C>T), RS1003862728 (12:6494853 C>T), RS1005525257 (12:6493669 G>A), RS1005663579 (12:6492575 G>A,C), RS1006014178 (12:6493835 G>A,T)

Disease associations

OMIM: gene MIM:611855 | 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: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Leflunomide	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
ICG 001	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Nickel	decreases expression	1
Ribonucleotides	affects binding	1
Thiram	decreases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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