MRPL36

Summary

MRPL36 (mitochondrial ribosomal protein L36, HGNC:14490) is a protein-coding gene on chromosome 5p15.33, encoding Large ribosomal subunit protein bL36m (Q9P0J6). It is a selective cancer dependency (DepMap: 58.0% 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 2p.

Source: NCBI Gene 64979 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 50 total
• Cancer dependency (DepMap): dependent in 58.0% of screened cell lines
• MANE Select transcript: NM_032479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14490
Approved symbol	MRPL36
Name	mitochondrial ribosomal protein L36
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	RPMJ, L36mt, PRPL36, MRP-L36, bL36m
Ensembl gene	ENSG00000171421
Ensembl biotype	protein_coding
OMIM	611842
Entrez	64979

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000382647, ENST00000505059, ENST00000505818, ENST00000508987, ENST00000510999, ENST00000887752, ENST00000887753, ENST00000887754, ENST00000933972, ENST00000933973, ENST00000933974

RefSeq mRNA: 1 — MANE Select: NM_032479 NM_032479

CCDS: CCDS3865

Canonical transcript exons

ENST00000505059 — 2 exons

Exon	Start	End
ENSE00002077583	1799792	1799837
ENSE00003842015	1798385	1798947

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.8682 / max 188.9301, expressed in 1801 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60825	15.0525	1782
60826	5.1578	1662
60824	3.0758	1504
60827	0.4618	281
60828	0.1203	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.44	gold quality
tibialis anterior	UBERON:0001385	98.65	gold quality
left ventricle myocardium	UBERON:0006566	98.12	gold quality
quadriceps femoris	UBERON:0001377	97.99	gold quality
vastus lateralis	UBERON:0001379	97.90	gold quality
deltoid	UBERON:0001476	97.74	gold quality
ileal mucosa	UBERON:0000331	97.53	gold quality
biceps brachii	UBERON:0001507	97.44	gold quality
left testis	UBERON:0004533	97.26	gold quality
right testis	UBERON:0004534	97.05	gold quality
kidney epithelium	UBERON:0004819	96.98	gold quality
adult organism	UBERON:0007023	96.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.96	gold quality
gastrocnemius	UBERON:0001388	96.80	gold quality
myocardium	UBERON:0002349	96.78	gold quality
heart right ventricle	UBERON:0002080	96.56	gold quality
testis	UBERON:0000473	96.55	gold quality
muscle of leg	UBERON:0001383	96.49	gold quality
body of tongue	UBERON:0011876	96.42	gold quality
skeletal muscle tissue	UBERON:0001134	96.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.12	gold quality
upper arm skin	UBERON:0004263	96.10	gold quality
sperm	CL:0000019	96.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.96	gold quality
muscle tissue	UBERON:0002385	95.87	gold quality
cardiac ventricle	UBERON:0002082	95.30	gold quality
heart left ventricle	UBERON:0002084	95.30	gold quality
gingiva	UBERON:0001828	95.25	gold quality
parotid gland	UBERON:0001831	95.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.73
E-GEOD-124858	no	165.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting MRPL36, 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-150-5P	99.99	66.69	1976
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-4522	95.76	66.23	742

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 58.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• MRPL36 contributes to the regulation of mitochondrial ATP production and necrotic cell death. (PMID:19318571)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrpl36	ENSDARG00000070607
mus_musculus	Mrpl36	ENSMUSG00000021607
rattus_norvegicus	Mrpl36	ENSRNOG00000023407
drosophila_melanogaster	mRpL36	FBGN0042112
caenorhabditis_elegans		WBGENE00010783

Protein

Protein identifiers

Large ribosomal subunit protein bL36m — Q9P0J6 (reviewed: Q9P0J6)

Alternative names: 39S ribosomal protein L36, mitochondrial, BRCA1-interacting protein 1

All UniProt accessions (2): D6RB74, Q9P0J6

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. bL36m has a zinc binding site.

Subcellular location. Mitochondrion.

Similarity. Belongs to the bacterial ribosomal protein bL36 family.

RefSeq proteins (1): NP_115868* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000473	Ribosomal_bL36	Family
IPR035977	Ribosomal_bL36_sp	Homologous_superfamily
IPR052143	Mitoribosomal_bL36m	Family

Pfam: PF00444

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

Structure

Experimental structures (PDB)

73 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7OF0	ELECTRON MICROSCOPY	2.2
7QI4	ELECTRON MICROSCOPY	2.21
8RRI	ELECTRON MICROSCOPY	2.4
9OLF	ELECTRON MICROSCOPY	2.46
7OF7	ELECTRON MICROSCOPY	2.5
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
8QSJ	ELECTRON MICROSCOPY	3
9UWH	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0J6-F1	73.15	0.41

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: 144 (showing top): MODULE_255, GOBP_MITOCHONDRIAL_TRANSLATION, MODULE_317, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, NIKOLSKY_BREAST_CANCER_5P15_AMPLICON, GARY_CD5_TARGETS_DN, WONG_MITOCHONDRIA_GENE_MODULE, MODULE_207, ZHOU_TNF_SIGNALING_30MIN, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, GOCC_ORGANELLAR_RIBOSOME

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 large ribosomal subunit (GO:0005762), nuclear body (GO:0016604), 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
intracellular membraneless organelle	2
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 large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
nucleoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

2935 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL36	MRPL17	Q9NRX2	647
MRPL36	MRPL1	Q9BYD6	646
MRPL36	MRPL24	Q96A35	628
MRPL36	MRPS16	Q9Y3D3	627
MRPL36	MRPL11	Q9Y3B7	626
MRPL36	MRPL12	P52815	595
MRPL36	MRPL21	Q7Z2W9	595
MRPL36	LETM1	O95202	593
MRPL36	MRPS11	P82912	572
MRPL36	MRPL9	Q9BYD2	530
MRPL36	RPL36	Q9Y3U8	529
MRPL36	MRPL13	Q9BYD1	528
MRPL36	MRPL4	Q9BYD3	526
MRPL36	MRPL19	P49406	524
MRPL36	MRPS10	P82664	513

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MRPL36	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
MRPL36	E7	psi-mi:“MI:0915”(physical association)	0.370
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
PSME3	ZNF891	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
GADD45GIP1		psi-mi:“MI:0915”(physical association)	0.320
	MRPL18	psi-mi:“MI:0915”(physical association)	0.320
RRAS	MRPL36	psi-mi:“MI:0915”(physical association)	0.000
MRPL36	CIDEB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): MRPL36 (Positive Genetic), MRPL36 (Negative Genetic), MRPL36 (Negative Genetic), MRPL36 (Positive Genetic), MRPL36 (Negative Genetic), MRPL36 (Negative Genetic), MRPL36 (Negative Genetic), MRPL36 (Positive Genetic), MRPL36 (Positive Genetic), MRPL42 (Positive Genetic), MRPS21 (Positive Genetic), MRPS35 (Positive Genetic), MRPS5 (Positive Genetic), GATB (Positive Genetic), TAZ (Negative Genetic)

ESM2 similar proteins: A6ZR01, A6ZRW2, A8NN94, B2RZ39, B3LS63, B5VHI3, F5HIJ5, G2TRP2, O13744, O13882, O14464, O74464, O94379, O94690, P12629, P25348, P25642, P32344, P32611, P36520, P36525, P36526, P38064, P38175, P40033, P42797, P42844, P49391, P53921, P82244, Q04598, Q09759, Q0E959, Q1K7P9, Q1LWG3, Q21454, Q54WP3, Q61JI9, Q6BIJ5, Q84JG5

Diamond homologs: A1BJ11, A1JS06, A2RC37, A4SCT2, A4WFA7, A5IMA7, A5VLI2, A6LLN7, A7HM28, A7MPF5, A7ZSI8, A8A5A4, A8F4T5, A9BFZ4, B1IQ00, B1JIY2, B1LBL6, B1LHB3, B1X6F1, B2G8V5, B2K516, B2RZ39, B3DFA8, B3EGW7, B3EP38, B3QR94, B3QYE6, B3WAJ5, B4F1K5, B4RT49, B4S5A5, B4SBX0, B4U523, B5XJ59, B7K227, B7KI08, B9DSX3, C0M6X5, C0ME28, C1BJQ3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL36	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

481 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1798948:C:CC	acceptor_gain	1.0000
5:1798943:TGAAT:T	acceptor_gain	0.9900
5:1798946:AT:A	acceptor_gain	0.9900
5:1798947:TCTA:T	acceptor_loss	0.9900
5:1798948:CTATG:C	acceptor_loss	0.9900
5:1798950:A:C	acceptor_gain	0.9900
5:1798944:GAAT:G	acceptor_gain	0.9800
5:1801546:CCAGG:C	donor_loss	0.9800
5:1801547:CAGG:C	donor_loss	0.9800
5:1801548:AG:A	donor_loss	0.9800
5:1801550:G:A	donor_loss	0.9800
5:1801551:T:A	donor_loss	0.9800
5:1798945:AAT:A	acceptor_gain	0.9700
5:1799791:CCCGG:C	donor_gain	0.9700
5:1801533:TC:T	donor_gain	0.9700
5:1798950:A:AC	acceptor_gain	0.9600
5:1799785:C:CA	donor_gain	0.9600
5:1799787:CTTA:C	donor_loss	0.9600
5:1799790:A:C	donor_loss	0.9600
5:1801671:T:TA	donor_gain	0.9500
5:1799496:TGCGG:T	donor_gain	0.9400
5:1799790:AC:A	donor_gain	0.9400
5:1799791:CC:C	donor_gain	0.9400
5:1801534:C:A	donor_gain	0.9400
5:1801777:G:T	donor_gain	0.9400
5:1801556:GCCGC:G	donor_gain	0.9300
5:1799790:A:AC	donor_gain	0.9200
5:1799791:C:CC	donor_gain	0.9200
5:1799792:C:G	donor_loss	0.9000
5:1801672:T:TA	donor_gain	0.9000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000952760 (5:1799340 C>A,T), RS1001074191 (5:1800857 T>G), RS1001375025 (5:1801508 C>G,T), RS1001422176 (5:1800551 G>C,T), RS1001783800 (5:1801736 G>A), RS1001884642 (5:1798478 A>C,G), RS1001959970 (5:1800098 T>G), RS1003153395 (5:1802405 G>A), RS1003248583 (5:1801314 C>G), RS1003422621 (5:1801307 TCCCCGCC>T,TCCCCGCCCCCCGCC), RS1003453227 (5:1802676 C>T), RS1003559103 (5:1799416 C>T), RS10037336 (5:1800024 C>G,T), RS1003887921 (5:1802628 T>A), RS1004422841 (5:1799873 G>A)

Disease associations

OMIM: gene MIM:611842 | disease phenotypes: MIM:618232, MIM:252010

GenCC curated gene-disease

Mondo (3): mitochondrial complex I deficiency, nuclear type 9 (MONDO:0032615), mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), mitochondrial complex I deficiency (MONDO:0100133)

Orphanet (1): Isolated complex I deficiency (Orphanet:2609)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006609_2	Response to TNF inhibitor in rheumatoid arthritis (change in tender 28-joint count)	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537475	Mitochondrial complex I deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
bisphenol A	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
chloropicrin	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Nanotubes, Carbon	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)