MRPL53

Summary

MRPL53 (mitochondrial ribosomal protein L53, HGNC:16684) is a protein-coding gene on chromosome 2p13.1, encoding Large ribosomal subunit protein mL53 (Q96EL3). It is a selective cancer dependency (DepMap: 75.9% 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. A pseudogene corresponding to this gene is found on chromosome 1p.

Source: NCBI Gene 116540 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• Cancer dependency (DepMap): dependent in 75.9% of screened cell lines
• MANE Select transcript: NM_053050

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16684
Approved symbol	MRPL53
Name	mitochondrial ribosomal protein L53
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	mL53
Ensembl gene	ENSG00000204822
Ensembl biotype	protein_coding
OMIM	611857
Entrez	116540

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000258105, ENST00000409710, ENST00000467349, ENST00000468875, ENST00000906488

RefSeq mRNA: 1 — MANE Select: NM_053050 NM_053050

CCDS: CCDS1944

Canonical transcript exons

ENST00000258105 — 3 exons

Exon	Start	End
ENSE00001868747	74472569	74472680
ENSE00001896436	74471982	74472252
ENSE00003659496	74472358	74472470

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 98.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.2192 / max 263.3670, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29214	54.2192	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	98.15	gold quality
right adrenal gland cortex	UBERON:0035827	97.99	gold quality
left adrenal gland cortex	UBERON:0035825	97.94	gold quality
left adrenal gland	UBERON:0001234	97.91	gold quality
heart left ventricle	UBERON:0002084	97.87	gold quality
apex of heart	UBERON:0002098	97.79	gold quality
gastrocnemius	UBERON:0001388	97.53	gold quality
monocyte	CL:0000576	97.46	gold quality
muscle of leg	UBERON:0001383	97.42	gold quality
leukocyte	CL:0000738	97.30	gold quality
right atrium auricular region	UBERON:0006631	97.20	gold quality
heart	UBERON:0000948	97.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.99	gold quality
body of stomach	UBERON:0001161	96.96	gold quality
mucosa of transverse colon	UBERON:0004991	96.95	gold quality
adult mammalian kidney	UBERON:0000082	96.92	gold quality
fundus of stomach	UBERON:0001160	96.91	gold quality
adrenal gland	UBERON:0002369	96.85	gold quality
left coronary artery	UBERON:0001626	96.81	gold quality
adenohypophysis	UBERON:0002196	96.69	gold quality
left ovary	UBERON:0002119	96.65	gold quality
body of pancreas	UBERON:0001150	96.64	gold quality
pituitary gland	UBERON:0000007	96.63	gold quality
right uterine tube	UBERON:0001302	96.63	gold quality
omental fat pad	UBERON:0010414	96.63	gold quality
granulocyte	CL:0000094	96.61	gold quality
right lobe of thyroid gland	UBERON:0001119	96.33	gold quality
right lobe of liver	UBERON:0001114	96.32	gold quality
substantia nigra	UBERON:0002038	96.32	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.90
E-GEOD-106540	no	120.52
E-MTAB-6108	no	87.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting MRPL53, 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-9902	99.89	69.15	2250
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-554	95.20	66.98	341

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 75.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• candidate gene for orofacial clefting (PMID:29053389)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mrpl53	ENSMUSG00000030037

Protein

Protein identifiers

Large ribosomal subunit protein mL53 — Q96EL3 (reviewed: Q96EL3)

Alternative names: 39S ribosomal protein L53, mitochondrial

All UniProt accessions (2): B9A051, Q96EL3

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. mL53 is located at the L7/L12 stalk.

Subcellular location. Mitochondrion.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mL53 family.

RefSeq proteins (1): NP_444278* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019716	Ribosomal_mL53	Family
IPR052473	mtLSU_mL53	Family

Pfam: PF10780

UniProt features (14 total): strand 7, helix 3, transit peptide 1, chain 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

83 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
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
8QSJ	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EL3-F1	81.55	0.18

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: 42 (showing top): YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_MITOCHONDRIAL_TRANSLATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_TRANSLATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_RIBOSOMAL_SUBUNIT, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOCC_MITOCHONDRIAL_PROTEIN_CONTAINING_COMPLEX, chr2p13

GO Biological Process (1): mitochondrial translation (GO:0032543)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), 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
mitochondrion	1
translation	1
mitochondrial gene expression	1
binding	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 membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL53	MRPL45	Q9BRJ2	616
MRPL53	MRPL50	Q8N5N7	570
MRPL53	MRPL40	Q9NQ50	548
MRPL53	MRPS31	Q92665	539
MRPL53	MRPS33	Q9Y291	534
MRPL53	CCDC90B	Q9GZT6	517
MRPL53	WDR74	Q6RFH5	509
MRPL53	MRPS18A	Q9NVS2	501
MRPL53	MRPS21	P82921	491
MRPL53	MRPL47	Q9HD33	491
MRPL53	C15orf62	A8K5M9	487
MRPL53	CCDC142	Q17RM4	475
MRPL53	MRPL51	Q4U2R6	472
MRPL53	MRPL46	Q9H2W6	467
MRPL53	MRPS18C	Q9Y3D5	450

IntAct

105 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
USP44	CETN2	psi-mi:“MI:0914”(association)	0.690
HNRNPH1	MRPL53	psi-mi:“MI:0915”(physical association)	0.670
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
MRPL53	KIF2A	psi-mi:“MI:0915”(physical association)	0.560
TAX1BP1	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
MRPL53	IKZF3	psi-mi:“MI:0915”(physical association)	0.560
MRPL53	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
KIF2A	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
SSX2IP	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
SMARCB1	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
PAX6	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
MRPL53	THAP1	psi-mi:“MI:0915”(physical association)	0.560
ELOB	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
GSC2	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
MRPL53	GATD3	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
ANKRD29	MRPL53	psi-mi:“MI:0915”(physical association)	0.560
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL10	ZZEF1	psi-mi:“MI:0914”(association)	0.530

BioGRID (247): MRPL53 (Two-hybrid), MRPL53 (Two-hybrid), MRPL53 (Two-hybrid), SSX2IP (Two-hybrid), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS), MRPL53 (Affinity Capture-MS)

ESM2 similar proteins: A2A825, A4F267, A6QR22, E9PZQ0, F1LMY4, O70422, O96008, P07144, P11716, P16960, P21817, P42055, P42056, P45880, P60027, P68002, P68003, P81155, P82013, P86223, Q1LZB5, Q29380, Q5E9L7, Q5R7V4, Q5RB44, Q5U3I0, Q5ZIW1, Q60930, Q60931, Q6P825, Q6PA35, Q75Q40, Q7F4F8, Q7ZTM6, Q7ZWS5, Q803G5, Q91W86, Q92759, Q969M1, Q96EL3

Diamond homologs: Q2HJF1, Q5RB44, Q96EL3, Q9D1H8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL53	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
VEGFR2 mediated cell proliferation	5	46.0×	3e-06
Mitochondrial ribosome-associated quality control	21	41.6×	8e-27
Mitochondrial translation	18	40.0×	7e-23
Mitochondrial translation initiation	19	38.9×	7e-24
Mitochondrial translation elongation	19	38.9×	7e-24
Mitochondrial translation termination	19	33.6×	9e-23
Translation	18	18.0×	2e-16

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	19	44.0×	5e-24
translation	10	13.7×	8e-07
negative regulation of translation	5	13.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

303 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74472330:C:A	donor_gain	1.0000
2:74472333:T:TA	donor_gain	1.0000
2:74472369:T:TA	donor_gain	1.0000
2:74472369:TCC:T	donor_gain	1.0000
2:74472370:C:A	donor_gain	1.0000
2:74472402:T:TA	donor_gain	1.0000
2:74472342:TCTCC:T	donor_gain	0.9900
2:74472344:TC:T	donor_gain	0.9900
2:74472345:C:CT	donor_gain	0.9900
2:74472557:T:TA	donor_gain	0.9900
2:74472558:C:A	donor_gain	0.9900
2:74472563:TCGTA:T	donor_loss	0.9900
2:74472564:CGTAC:C	donor_loss	0.9900
2:74472566:TACC:T	donor_loss	0.9900
2:74472568:C:CG	donor_loss	0.9900
2:74472250:CTC:C	acceptor_gain	0.9800
2:74472253:C:CC	acceptor_gain	0.9800
2:74472346:C:CT	donor_gain	0.9800
2:74472376:A:AC	donor_gain	0.9800
2:74472252:CCT:C	acceptor_loss	0.9700
2:74472253:CT:C	acceptor_loss	0.9700
2:74472254:T:G	acceptor_loss	0.9700
2:74472361:A:C	donor_gain	0.9700
2:74472399:A:AC	donor_gain	0.9700
2:74472399:ACGT:A	donor_gain	0.9700
2:74472400:C:CC	donor_gain	0.9700
2:74472400:CGT:C	donor_gain	0.9700
2:74472400:CGTC:C	donor_gain	0.9700
2:74472568:CCT:C	donor_gain	0.9700
2:74472251:TC:T	acceptor_gain	0.9600

AlphaMissense

724 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:74472416:G:C	C49W	0.988
2:74472592:G:C	F23L	0.988
2:74472592:G:T	F23L	0.988
2:74472594:A:G	F23L	0.988
2:74472470:C:A	R31S	0.987
2:74472470:C:G	R31S	0.987
2:74472465:A:G	F33S	0.984
2:74472569:C:A	R31M	0.984
2:74472569:C:G	R31T	0.984
2:74472418:A:G	C49R	0.983
2:74472372:A:T	V64E	0.978
2:74472464:G:C	F33L	0.978
2:74472464:G:T	F33L	0.978
2:74472466:A:G	F33L	0.978
2:74472417:C:T	C49Y	0.977
2:74472602:A:G	F20S	0.977
2:74472614:A:T	V16D	0.977
2:74472453:A:T	V37E	0.976
2:74472366:A:T	V66E	0.975
2:74472623:A:T	V13D	0.975
2:74472226:C:G	G78R	0.974
2:74472608:A:T	V18D	0.974
2:74472425:A:C	N46K	0.971
2:74472425:A:T	N46K	0.971
2:74472359:G:C	F68L	0.970
2:74472359:G:T	F68L	0.970
2:74472361:A:G	F68L	0.970
2:74472601:G:C	F20L	0.970
2:74472601:G:T	F20L	0.970
2:74472603:A:G	F20L	0.970

dbSNP variants (sampled 300 via entrez): RS1000866090 (2:74474445 G>A,C), RS1000870266 (2:74472763 C>G), RS1002032833 (2:74472963 C>G,T), RS1002085195 (2:74472777 G>A,C), RS1002107829 (2:74472086 G>A), RS1003696017 (2:74474473 C>T), RS1003762878 (2:74474191 C>T), RS1004102630 (2:74472720 G>A,C), RS1006563631 (2:74473455 G>C), RS1006678374 (2:74473314 C>T), RS1008461451 (2:74472555 C>T), RS1009950126 (2:74474418 C>T), RS1010001678 (2:74474069 G>A), RS1011468129 (2:74471481 A>G), RS1011471610 (2:74473679 T>C,G)

Disease associations

OMIM: gene MIM:611857 | 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

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	2
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	increases expression	1
corosolic acid	decreases expression	1
bisphenol AF	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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