MRPS12

Summary

MRPS12 (mitochondrial ribosomal protein S12, HGNC:10380) is a protein-coding gene on chromosome 19q13.2, encoding Small ribosomal subunit protein uS12m (O15235). It is a selective cancer dependency (DepMap: 67.6% 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 28S subunit protein that belongs to the ribosomal protein S12P family. The encoded protein is a key component of the ribosomal small subunit and controls the decoding fidelity and susceptibility to aminoglycoside antibiotics. The gene for mitochondrial seryl-tRNA synthetase is located upstream and adjacent to this gene, and both genes are possible candidates for the autosomal dominant deafness gene (DFNA4). Splice variants that differ in the 5’ UTR have been found for this gene; all three variants encode the same protein.

Source: NCBI Gene 6183 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• Cancer dependency (DepMap): dependent in 67.6% of screened cell lines
• MANE Select transcript: NM_033362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10380
Approved symbol	MRPS12
Name	mitochondrial ribosomal protein S12
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	RPS12, RPSM12, uS12m
Ensembl gene	ENSG00000128626
Ensembl biotype	protein_coding
OMIM	603021
Entrez	6183

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000308018, ENST00000402029, ENST00000407800, ENST00000598734, ENST00000899577, ENST00000933522, ENST00000933523, ENST00000933524, ENST00000968236

RefSeq mRNA: 3 — MANE Select: NM_033362 NM_021107, NM_033362, NM_033363

CCDS: CCDS12525

Canonical transcript exons

ENST00000308018 — 3 exons

Exon	Start	End
ENSE00001199341	38931276	38931343
ENSE00003038280	38930944	38930998
ENSE00003906959	38932333	38933168

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 96.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.8697 / max 270.1536, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175676	58.8697	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.84	gold quality
mucosa of transverse colon	UBERON:0004991	95.96	gold quality
heart left ventricle	UBERON:0002084	95.07	gold quality
right atrium auricular region	UBERON:0006631	94.31	gold quality
heart	UBERON:0000948	93.17	gold quality
right lobe of liver	UBERON:0001114	92.83	gold quality
adult mammalian kidney	UBERON:0000082	92.60	gold quality
right adrenal gland	UBERON:0001233	92.46	gold quality
gastrocnemius	UBERON:0001388	92.35	gold quality
left adrenal gland	UBERON:0001234	92.17	gold quality
body of stomach	UBERON:0001161	92.14	gold quality
lower esophagus mucosa	UBERON:0035834	92.14	gold quality
left adrenal gland cortex	UBERON:0035825	92.11	gold quality
right adrenal gland cortex	UBERON:0035827	92.02	gold quality
esophagus mucosa	UBERON:0002469	91.89	gold quality
metanephros cortex	UBERON:0010533	91.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.59	gold quality
muscle of leg	UBERON:0001383	91.42	gold quality
cortex of kidney	UBERON:0001225	91.20	gold quality
transverse colon	UBERON:0001157	90.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.92	gold quality
granulocyte	CL:0000094	90.48	gold quality
fundus of stomach	UBERON:0001160	90.33	gold quality
adrenal gland	UBERON:0002369	90.26	gold quality
esophagus	UBERON:0001043	90.08	gold quality
prefrontal cortex	UBERON:0000451	89.89	gold quality
skin of leg	UBERON:0001511	89.45	gold quality
spleen	UBERON:0002106	89.39	gold quality
body of pancreas	UBERON:0001150	89.33	gold quality
skin of abdomen	UBERON:0001416	89.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting MRPS12, 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-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-505-5P	97.01	65.54	778

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 67.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Homo sapiens mitochondrial ribosomal protein S12 (PMID:12706105)
• mitochondrial ribosomal protein S12 3’-UTR interacts specifically with TRAP1 (tumor necrosis factor receptor-associated protein1), hnRNPM4 (heterogeneous nuclear ribonucleoprotein M4), Hsp70 and Hsp60 (heat shock proteins 70 and 60), and alpha-tubulin (PMID:18790094)
• NF-Y type CCAAT boxes are found preferentially in bidirectional Mrps12/Sarsm promoters, but many such promoters lack them and must be regulated in another way. (PMID:19439209)
• A novel biomarker, MRPS12 functions as a potential oncogene in ovarian cancer and is a promising prognostic candidate. (PMID:33663122)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrps12	ENSDARG00000089836
mus_musculus	Mrps12	ENSMUSG00000045948
rattus_norvegicus	Mrps12	ENSRNOG00000019949
drosophila_melanogaster	tko	FBGN0003714
caenorhabditis_elegans		WBGENE00011391

Paralogs (1): RPS23 (ENSG00000186468)

Protein

Protein identifiers

Small ribosomal subunit protein uS12m — O15235 (reviewed: O15235)

Alternative names: 28S ribosomal protein S12, mitochondrial, MT-RPS12

All UniProt accessions (1): O15235

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the mitochondrial small ribosomal subunit (mt-SSU). 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 uS12 family.

RefSeq proteins (3): NP_066930, NP_203526, NP_203527 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005679	Ribosomal_uS12_bact	Family
IPR006032	Ribosomal_uS12	Family
IPR012340	NA-bd_OB-fold	Homologous_superfamily

Pfam: PF00164

UniProt features (12 total): strand 6, transit peptide 1, chain 1, region of interest 1, sequence variant 1, helix 1, turn 1

Structure

Experimental structures (PDB)

77 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7QI4	ELECTRON MICROSCOPY	2.21
8CSS	ELECTRON MICROSCOPY	2.36
7P2E	ELECTRON MICROSCOPY	2.4
8RRI	ELECTRON MICROSCOPY	2.4
9OLF	ELECTRON MICROSCOPY	2.46
9OJM	ELECTRON MICROSCOPY	2.5
8CSQ	ELECTRON MICROSCOPY	2.54
8CSR	ELECTRON MICROSCOPY	2.54
6ZM6	ELECTRON MICROSCOPY	2.59
7QI5	ELECTRON MICROSCOPY	2.63
8CSP	ELECTRON MICROSCOPY	2.66
7PNX	ELECTRON MICROSCOPY	2.76
8ANY	ELECTRON MICROSCOPY	2.85
8CST	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
7PO0	ELECTRON MICROSCOPY	2.9
8K2A	ELECTRON MICROSCOPY	2.9
9PGL	ELECTRON MICROSCOPY	2.9
7PO1	ELECTRON MICROSCOPY	2.92
7PO3	ELECTRON MICROSCOPY	2.92
9PGF	ELECTRON MICROSCOPY	2.93
6VMI	ELECTRON MICROSCOPY	2.96
6RW4	ELECTRON MICROSCOPY	2.97
6VLZ	ELECTRON MICROSCOPY	2.97
7QI6	ELECTRON MICROSCOPY	2.98
8QRN	ELECTRON MICROSCOPY	2.98
9PSM	ELECTRON MICROSCOPY	2.98
8OIS	ELECTRON MICROSCOPY	3
9G5C	ELECTRON MICROSCOPY	3
9G5D	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15235-F1	86.81	0.78

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: 386 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, ELVIDGE_HYPOXIA_DN, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BASSO_B_LYMPHOCYTE_NETWORK, GNF2_TPT1, ENK_UV_RESPONSE_KERATINOCYTE_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_HDAC1, GOBP_MITOCHONDRIAL_TRANSLATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY

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

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

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial ribosome (GO:0005761), mitochondrial small ribosomal subunit (GO:0005763), ribosome (GO:0005840), small ribosomal subunit (GO:0015935), 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
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 ribosome	1
mitochondrial matrix	1
organellar small 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

4400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPS12	MYH14	Q7Z406	939
MRPS12	BAX	P55269	763
MRPS12	MRPL32	Q9BYC8	625
MRPS12	MRPS11	P82912	617
MRPS12	MRPL12	P52815	616
MRPS12	MRPL17	Q9NRX2	607
MRPS12	DMPK	Q09013	586
MRPS12	GJB2	P29033	582
MRPS12	MRPL2	Q5T653	565
MRPS12	IMP4	Q96G21	544
MRPS12	RPS12	P25398	536
MRPS12	TUFM	P49411	508
MRPS12	MRPS15	P82914	493
MRPS12	MRPS16	Q9Y3D3	490
MRPS12	MT-CO1	P00395	458

IntAct

84 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
TEFM	POLRMT	psi-mi:“MI:0914”(association)	0.560
MRPS12	SPINK7	psi-mi:“MI:0915”(physical association)	0.550
SPINK7	MRPS12	psi-mi:“MI:0915”(physical association)	0.550
DKK3	NME4	psi-mi:“MI:0914”(association)	0.530
MRPS12	MTIF2	psi-mi:“MI:0914”(association)	0.530
MRPS34	MRPS12	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
Cdc23	ANAPC15	psi-mi:“MI:0914”(association)	0.350
CKAP5	TACC3	psi-mi:“MI:0914”(association)	0.350
Kif2c	MRPS12	psi-mi:“MI:0914”(association)	0.350
ZSCAN5A	MRPS12	psi-mi:“MI:0914”(association)	0.350
USP43	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
MPHOSPH8	HCFC1	psi-mi:“MI:0914”(association)	0.350
Nfyc	BDP1	psi-mi:“MI:0914”(association)	0.350
Dctn1	DERL1	psi-mi:“MI:0914”(association)	0.350
E7	COPE	psi-mi:“MI:0914”(association)	0.350
CDK7	SEC16A	psi-mi:“MI:0914”(association)	0.350
EEA1	SEC16A	psi-mi:“MI:0914”(association)	0.350
MAD2L2		psi-mi:“MI:0914”(association)	0.350
SMARCB1		psi-mi:“MI:0914”(association)	0.350

BioGRID (263): MRPS12 (Co-fractionation), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), MRPS12 (Two-hybrid), MRPS12 (Proximity Label-MS), MRPS12 (Affinity Capture-MS)

ESM2 similar proteins: A0L5W8, A2C4U8, A2CC84, A2T357, A4GGC9, A4GYT5, A4SCQ4, A4TGY4, A9ETB7, B0SUQ4, B2RLZ6, B3EH96, B3QR56, B4R8L1, B4S5N2, B4SBU2, B6EPR5, B7VLG2, C1DKK7, O14182, O15235, O35680, P07134, P10735, P53732, Q056Z9, Q0BYA9, Q0G9J5, Q14FB1, Q15YA9, Q1ACP3, Q1KXY0, Q1LSY7, Q20EW0, Q29RU1, Q32RQ9, Q332V3, Q3APG8, Q46IW1, Q49KX4

Diamond homologs: A0A1D8PDU3, A0B562, A0RUR2, A1E9Q2, A1E9Y6, A1RSE4, A1RWW1, A2BN38, A2STX1, A3CXN0, A3DMP8, A3MXZ4, A4FWF2, A4WNA3, A5ULM8, A6UV46, A6VGV3, A7I4X6, A8A929, B0R8D1, G1SZ47, O15235, O27129, O28387, O35680, O59229, P06147, P0C460, P0C461, P0CT75, P0CT76, P0CX00, P0CX29, P0CX30, P0CY39, P0CY40, P10735, P11524, P12149, P12340

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPS12	“form complex”	“28S mitochondrial small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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 translation initiation	8	16.1×	1e-05
Mitochondrial translation	7	15.3×	6e-05
Mitochondrial translation elongation	7	14.1×	7e-05
Mitochondrial ribosome-associated quality control	7	13.6×	7e-05
Mitochondrial translation termination	7	12.2×	1e-04
ER to Golgi Anterograde Transport	5	10.5×	4e-03
Recruitment of NuMA to mitotic centrosomes	5	9.2×	5e-03
EML4 and NUDC in mitotic spindle formation	6	8.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	7	13.7×	5e-04
microtubule cytoskeleton organization	7	9.5×	3e-03
cell division	10	5.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

812 predictions. Top by Δscore:

Variant	Effect	Δscore
19:38931341:GTG:G	donor_gain	1.0000
19:38932331:A:AG	acceptor_gain	1.0000
19:38932332:G:GG	acceptor_gain	1.0000
6:132814611:GGG:G	donor_gain	1.0000
6:132814612:GG:G	donor_gain	1.0000
6:132814612:GGG:G	donor_gain	1.0000
6:132814613:GG:G	donor_gain	1.0000
6:132814614:G:GG	donor_gain	1.0000
6:132814614:GT:G	donor_loss	1.0000
6:132814615:T:A	donor_loss	1.0000
6:132814730:A:AG	acceptor_gain	1.0000
6:132814731:G:GG	acceptor_gain	1.0000
6:132814731:GT:G	acceptor_gain	1.0000
6:132814731:GTGC:G	acceptor_gain	1.0000
6:132814778:G:GT	donor_gain	1.0000
6:132814779:A:T	donor_gain	1.0000
6:132814781:GG:G	donor_gain	1.0000
6:132814782:GG:G	donor_gain	1.0000
6:132814970:A:G	acceptor_gain	1.0000
6:132815014:A:G	acceptor_gain	1.0000
6:132815089:G:GG	donor_gain	1.0000
6:132816451:T:TA	acceptor_gain	1.0000
6:132816455:TTTCA:T	acceptor_loss	1.0000
6:132816457:TCA:T	acceptor_loss	1.0000
6:132816459:A:AG	acceptor_gain	1.0000
6:132816459:AG:A	acceptor_gain	1.0000
6:132816459:AGGC:A	acceptor_gain	1.0000
6:132816460:G:GT	acceptor_gain	1.0000
6:132816460:GG:G	acceptor_gain	1.0000
6:132816460:GGC:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000951164 (19:38932831 G>A), RS1001086937 (19:38933025 C>T), RS1002035764 (19:38933428 C>T), RS1002300430 (19:38929989 T>C), RS1002436163 (19:38929777 C>A,G,T), RS1002505771 (19:38932616 G>C), RS1002637535 (19:38931034 G>A,T), RS1004348213 (19:38929684 C>T), RS1004358856 (19:38929383 T>C), RS1004949966 (19:38933586 G>A,T), RS1005101081 (19:38930564 A>C,G,T), RS1005389149 (19:38933357 A>G), RS1005987074 (19:38932237 T>A), RS1006634693 (19:38933165 C>A,T), RS1007094761 (19:38932874 G>A)

Disease associations

OMIM: gene MIM:603021 | 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

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, decreases expression	3
Valproic Acid	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-hydroxy-equilenin	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, decreases expression	1
MT19c compound	decreases expression	1
Bortezomib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Calcitriol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydralazine	increases expression, affects cotreatment	1
Lead	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
Aflatoxin B1	increases expression	1
Asbestos, Crocidolite	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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