MRPL1

Summary

MRPL1 (mitochondrial ribosomal protein L1, HGNC:14275) is a protein-coding gene on chromosome 4q21.1, encoding Large ribosomal subunit protein uL1m (Q9BYD6). It is a selective cancer dependency (DepMap: 11.4% 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 that belongs to the L1 ribosomal protein family.

Source: NCBI Gene 65008 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 57 total
• Cancer dependency (DepMap): dependent in 11.4% of screened cell lines
• MANE Select transcript: NM_020236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14275
Approved symbol	MRPL1
Name	mitochondrial ribosomal protein L1
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	BM022, uL1m
Ensembl gene	ENSG00000169288
Ensembl biotype	protein_coding
OMIM	611821
Entrez	65008

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000315567, ENST00000502384, ENST00000504901, ENST00000506674, ENST00000511521, ENST00000515625, ENST00000865377, ENST00000865378, ENST00000865379, ENST00000915229, ENST00000915230

RefSeq mRNA: 1 — MANE Select: NM_020236 NM_020236

CCDS: CCDS3583

Canonical transcript exons

ENST00000315567 — 9 exons

Exon	Start	End
ENSE00001140502	77949797	77949878
ENSE00001140507	77909266	77909372
ENSE00001522312	77952489	77952785
ENSE00001522345	77862830	77862879
ENSE00003497142	77883242	77883500
ENSE00003548653	77885256	77885339
ENSE00003586620	77894139	77894250
ENSE00003652051	77887220	77887291
ENSE00003679813	77871744	77871855

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 95.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.7090 / max 531.8351, expressed in 1790 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48429	19.9612	1781
48428	2.9582	1287
48427	0.7897	490

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	95.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.96	gold quality
deltoid	UBERON:0001476	94.74	gold quality
biceps brachii	UBERON:0001507	94.69	gold quality
quadriceps femoris	UBERON:0001377	94.32	gold quality
vastus lateralis	UBERON:0001379	94.21	gold quality
tibialis anterior	UBERON:0001385	94.19	gold quality
skeletal muscle tissue	UBERON:0001134	93.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.71	gold quality
adrenal tissue	UBERON:0018303	93.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.63	gold quality
muscle tissue	UBERON:0002385	93.43	gold quality
myocardium	UBERON:0002349	93.25	gold quality
skeletal muscle organ	UBERON:0014892	93.23	gold quality
muscle of leg	UBERON:0001383	92.99	gold quality
mucosa of transverse colon	UBERON:0004991	92.94	gold quality
rectum	UBERON:0001052	92.93	gold quality
gastrocnemius	UBERON:0001388	92.88	gold quality
embryo	UBERON:0000922	92.85	gold quality
ganglionic eminence	UBERON:0004023	92.85	gold quality
heart left ventricle	UBERON:0002084	92.59	gold quality
cardiac ventricle	UBERON:0002082	92.49	gold quality
cortical plate	UBERON:0005343	92.30	gold quality
islet of Langerhans	UBERON:0000006	91.95	gold quality
heart right ventricle	UBERON:0002080	91.81	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.78	silver quality
ventricular zone	UBERON:0003053	91.49	gold quality
heart	UBERON:0000948	91.46	gold quality
smooth muscle tissue	UBERON:0001135	90.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.62
E-CURD-112	no	3.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting MRPL1, 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-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-943	97.81	64.42	694
HSA-MIR-526B-5P	97.41	67.99	1074

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• MLRP1 could possibly serve as a candidate gene for alterations associated with asbestos exposure. (PMID:26463840)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrpl1	ENSDARG00000054606
mus_musculus	Mrpl1	ENSMUSG00000029486
rattus_norvegicus	Mrpl1	ENSRNOG00000002070

Protein

Protein identifiers

Large ribosomal subunit protein uL1m — Q9BYD6 (reviewed: Q9BYD6)

Alternative names: 39S ribosomal protein L1, mitochondrial

All UniProt accessions (2): Q9BYD6, H0Y8N7

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 universal ribosomal protein uL1 family.

RefSeq proteins (1): NP_064621* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005879	Ribosomal_uL1_mit	Family
IPR016095	Ribosomal_uL1_3-a/b-sand	Homologous_superfamily
IPR023674	Ribosomal_uL1-like	Homologous_superfamily
IPR028364	Ribosomal_uL1/biogenesis	Family

Pfam: PF00687

UniProt features (7 total): sequence conflict 3, sequence variant 2, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
7QI4	ELECTRON MICROSCOPY	2.21
8RRI	ELECTRON MICROSCOPY	2.4
9OLF	ELECTRON MICROSCOPY	2.46
7QI5	ELECTRON MICROSCOPY	2.63
9PR4	ELECTRON MICROSCOPY	2.77
9PRA	ELECTRON MICROSCOPY	2.83
8ANY	ELECTRON MICROSCOPY	2.85
8OIT	ELECTRON MICROSCOPY	2.9
7QI6	ELECTRON MICROSCOPY	2.98
9PSM	ELECTRON MICROSCOPY	2.98
9PGI	ELECTRON MICROSCOPY	3.02
9PG8	ELECTRON MICROSCOPY	3.06
9PS7	ELECTRON MICROSCOPY	3.08
8OIR	ELECTRON MICROSCOPY	3.1
9PSI	ELECTRON MICROSCOPY	3.12
9PGM	ELECTRON MICROSCOPY	3.18
9PS0	ELECTRON MICROSCOPY	3.29
7A5K	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYD6-F1	78.90	0.56

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: 137 (showing top): GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, YY1_02, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, PPAR_DR1_Q2, GARY_CD5_TARGETS_DN, AACTTT_UNKNOWN, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, chr4q21, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME

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

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

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial large ribosomal subunit (GO:0005762), ribosome (GO:0005840), large ribosomal subunit (GO:0015934), 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
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
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
ribosomal subunit	1
protein-containing complex	1

Protein interactions and networks

STRING

3254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL1	MRPL36	Q9P0J6	646
MRPL1	MRPL46	Q9H2W6	618
MRPL1	MRPL2	Q5T653	593
MRPL1	MRPL4	Q9BYD3	567
MRPL1	MRPL24	Q96A35	564
MRPL1	MRPL11	Q9Y3B7	559
MRPL1	MRPL52	Q86TS9	557
MRPL1	MRPS18A	Q9NVS2	557
MRPL1	MRPL12	P52815	549
MRPL1	MRPL13	Q9BYD1	547
MRPL1	MRPL54	Q6P161	547
MRPL1	MRPS18C	Q9Y3D5	543
MRPL1	MRPL40	Q9NQ50	538
MRPL1	MRPL20	Q9BYC9	536
MRPL1	MRPL39	Q9NYK5	534
MRPL1	MRPL19	P49406	534

IntAct

170 interactions, top by confidence:

A	B	Type	Score
NDUFAF1	NDUFS3	psi-mi:“MI:0914”(association)	0.790
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
COQ5	COQ9	psi-mi:“MI:0914”(association)	0.590
MRPL1	GOPC	psi-mi:“MI:0915”(physical association)	0.560
VPS52	MRPL1	psi-mi:“MI:0915”(physical association)	0.560
SPAG16	MRPL1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPD	HNRNPDL	psi-mi:“MI:0914”(association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
CIRBP	PRMT5	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
MRPL28	MRPL3	psi-mi:“MI:0914”(association)	0.530
MRPL41	MRPL3	psi-mi:“MI:0914”(association)	0.530
YBX1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
HNRNPA1	PTCD1	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	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

BioGRID (259): MRPL1 (Two-hybrid), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), MRPL1 (Affinity Capture-MS), ATP6V1H (Co-fractionation), CORO1B (Co-fractionation), MRPL1 (Co-fractionation), MRPL1 (Co-fractionation)

ESM2 similar proteins: A5D7S3, A5PKL6, A6NHR9, A6NNW6, A6QPQ5, A6QPR9, A8K855, O02789, O75717, P27641, P59328, P60670, P82933, Q0IHV1, Q2T9V5, Q32KZ1, Q496Z9, Q4R6C7, Q4R6Y8, Q58DQ5, Q5F204, Q5M882, Q5R5T0, Q5R952, Q5RL51, Q5TZF3, Q69ZX6, Q6AZN0, Q6DDT5, Q6P5D8, Q7Z2T5, Q8CE96, Q8NEC7, Q8R3N6, Q8TAT6, Q8VDY4, Q8VI84, Q8WTT2, Q91Y26, Q96FV9

Diamond homologs: A6QPQ5, Q2S1Q2, Q99N96, Q9BYD6, Q7UI03

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL1	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 141 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	31	35.9×	1e-38
Mitochondrial translation	27	35.0×	1e-33
Mitochondrial translation initiation	29	34.7×	6e-36
Mitochondrial translation elongation	29	34.7×	6e-36
Mitochondrial translation termination	29	30.0×	6e-34
Translation	29	17.0×	3e-26
Peptide chain elongation	9	10.8×	7e-06
Viral mRNA Translation	9	10.8×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	31	42.4×	3e-40
positive regulation of cytoplasmic translation	5	39.0×	1e-05
translation	25	20.2×	2e-23
negative regulation of translation	9	13.9×	3e-06
cytoplasmic translation	9	13.1×	3e-06
regulation of alternative mRNA splicing, via spliceosome	6	11.5×	9e-04
mRNA transport	5	10.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1355 predictions. Top by Δscore:

Variant	Effect	Δscore
4:77871727:AT:A	acceptor_gain	1.0000
4:77871728:T:G	acceptor_gain	1.0000
4:77871741:A:AG	acceptor_gain	1.0000
4:77871742:A:G	acceptor_gain	1.0000
4:77871743:G:GA	acceptor_gain	1.0000
4:77871743:GCC:G	acceptor_gain	1.0000
4:77871743:GCCT:G	acceptor_gain	1.0000
4:77871743:GCCTT:G	acceptor_gain	1.0000
4:77871851:ACAAA:A	donor_gain	1.0000
4:77871852:CAAA:C	donor_gain	1.0000
4:77871853:AAA:A	donor_gain	1.0000
4:77871853:AAAG:A	donor_loss	1.0000
4:77871854:AA:A	donor_gain	1.0000
4:77871855:AG:A	donor_loss	1.0000
4:77871856:G:GG	donor_gain	1.0000
4:77871857:TAAG:T	donor_loss	1.0000
4:77883240:A:G	acceptor_gain	1.0000
4:77883348:G:GT	donor_gain	1.0000
4:77885247:T:G	acceptor_gain	1.0000
4:77887214:T:TA	acceptor_gain	1.0000
4:77887217:TA:T	acceptor_loss	1.0000
4:77887218:A:AG	acceptor_gain	1.0000
4:77887218:AGA:A	acceptor_loss	1.0000
4:77887219:G:GG	acceptor_gain	1.0000
4:77887219:GA:G	acceptor_gain	1.0000
4:77887219:GAAT:G	acceptor_gain	1.0000
4:77887288:GAAG:G	donor_gain	1.0000
4:77894130:A:AG	acceptor_gain	1.0000
4:77894134:TTCAG:T	acceptor_loss	1.0000
4:77894135:TCAG:T	acceptor_loss	1.0000

AlphaMissense

2157 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:77952518:A:C	S297R	0.993
4:77952520:T:A	S297R	0.993
4:77952520:T:G	S297R	0.993
4:77949831:T:C	L271P	0.989
4:77894175:G:C	A199P	0.986
4:77952527:A:C	S300R	0.984
4:77952529:T:A	S300R	0.984
4:77952529:T:G	S300R	0.984
4:77885329:T:A	V159E	0.983
4:77883415:T:C	L106P	0.982
4:77909368:C:A	A258E	0.982
4:77909367:G:C	A258P	0.981
4:77952516:G:C	R296P	0.979
4:77883460:T:A	V121D	0.978
4:77885332:T:C	F160S	0.978
4:77883355:T:A	V86D	0.974
4:77952498:T:A	V290E	0.974
4:77952507:C:A	A293D	0.974
4:77883402:G:C	A102P	0.973
4:77887242:C:A	A170E	0.973
4:77885323:T:A	V157D	0.972
4:77909365:T:A	I257K	0.972
4:77949829:T:A	N270K	0.970
4:77949829:T:G	N270K	0.970
4:77894173:T:A	V198E	0.968
4:77894176:C:A	A199D	0.968
4:77883478:T:C	L127P	0.967
4:77952504:G:C	R292P	0.967
4:77952513:T:C	L295P	0.965
4:77952513:T:G	L295R	0.965

dbSNP variants (sampled 300 via entrez): RS1000020507 (4:77950361 A>G), RS1000032632 (4:77920518 G>A), RS1000046904 (4:77895739 T>A), RS1000088843 (4:77895493 G>C), RS1000119969 (4:77895860 T>G), RS1000173479 (4:77923342 C>T), RS1000200455 (4:77902921 A>G), RS1000236852 (4:77928810 TTTA>T), RS1000306621 (4:77910383 G>A,C), RS1000381357 (4:77881842 G>A), RS1000392181 (4:77888067 C>T), RS1000476212 (4:77888382 G>A,T), RS1000480944 (4:77942561 A>C,G), RS1000483787 (4:77909371 C>G,T), RS1000491044 (4:77943831 C>G)

Disease associations

OMIM: gene MIM:611821 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003542_16	Night sleep phenotypes	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Valproic Acid	affects expression, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
pinostrobin	increases phosphorylation	1
ICG 001	affects expression	1
jinfukang	decreases expression	1
NSC 689534	decreases expression	1
MT19c compound	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
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Curcumin	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

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