MRPL12

Summary

MRPL12 (mitochondrial ribosomal protein L12, HGNC:10378) is a protein-coding gene on chromosome 17q25.3, encoding Large ribosomal subunit protein bL12m (P52815). As a component of the mitochondrial large ribosomal subunit, plays a role in mitochondrial translation. It is a selective cancer dependency (DepMap: 45.6% 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 39S subunit protein which forms homodimers. In prokaryotic ribosomes, two L7/L12 dimers and one L10 protein form the L8 protein complex.

Source: NCBI Gene 6182 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 126 total — 1 pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 45.6% of screened cell lines
• MANE Select transcript: NM_002949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10378
Approved symbol	MRPL12
Name	mitochondrial ribosomal protein L12
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	MRPL7/L12, MRPL7, bL12m
Ensembl gene	ENSG00000262814
Ensembl biotype	protein_coding
OMIM	602375
Entrez	6182

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000333676, ENST00000853971, ENST00000913226

RefSeq mRNA: 1 — MANE Select: NM_002949 NM_002949

CCDS: CCDS11785

Canonical transcript exons

ENST00000333676 — 5 exons

Exon	Start	End
ENSE00001308914	81707124	81707517
ENSE00002653318	81703367	81703575
ENSE00003678467	81706906	81707040
ENSE00003721539	81704244	81704430
ENSE00003748927	81704633	81704716

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 100.2607 / max 712.3178, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163354	60.6819	1810
163353	37.6195	1823
163355	1.2276	634
163356	0.6194	335
163352	0.1123	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.98	gold quality
mucosa of transverse colon	UBERON:0004991	98.45	gold quality
heart left ventricle	UBERON:0002084	98.20	gold quality
right atrium auricular region	UBERON:0006631	97.38	gold quality
right lobe of liver	UBERON:0001114	97.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.32	gold quality
gastrocnemius	UBERON:0001388	97.08	gold quality
heart	UBERON:0000948	96.50	gold quality
muscle of leg	UBERON:0001383	96.14	gold quality
esophagus mucosa	UBERON:0002469	95.93	gold quality
lower esophagus mucosa	UBERON:0035834	95.84	gold quality
transverse colon	UBERON:0001157	95.83	gold quality
adult mammalian kidney	UBERON:0000082	95.76	gold quality
skeletal muscle tissue	UBERON:0001134	95.31	gold quality
right adrenal gland	UBERON:0001233	95.30	gold quality
right adrenal gland cortex	UBERON:0035827	95.21	gold quality
left adrenal gland	UBERON:0001234	94.99	gold quality
vastus lateralis	UBERON:0001379	94.96	gold quality
left adrenal gland cortex	UBERON:0035825	94.93	gold quality
putamen	UBERON:0001874	94.81	gold quality
substantia nigra	UBERON:0002038	94.72	gold quality
liver	UBERON:0002107	94.41	gold quality
metanephros cortex	UBERON:0010533	94.37	gold quality
esophagus	UBERON:0001043	94.21	gold quality
body of stomach	UBERON:0001161	94.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.11	gold quality
hypothalamus	UBERON:0001898	94.07	gold quality
nucleus accumbens	UBERON:0001882	94.05	gold quality
caudate nucleus	UBERON:0001873	93.99	gold quality
colon	UBERON:0001155	93.95	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	41.01
E-CURD-112	yes	27.57
E-MTAB-8271	yes	9.33
E-ANND-3	yes	9.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting MRPL12, 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-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-558	97.50	67.16	977

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• the MRPL12 interaction with POLRMT is likely part of a novel regulatory mechanism that coordinates mitochondrial transcription with translation (PMID:17337445)
• This mutation resulted in a decreased steady-state level of MRPL12 protein. (PMID:23603806)
• knock-down of MRPL12 by RNA interference results in instability of POLRMT. (PMID:26586915)
• Transcription of MRPL12 regulated by Nrf2 contributes to the mitochondrial dysfunction in diabetic kidney disease. (PMID:33444714)
• MRPL12 Acts as A Novel Prognostic Biomarker Involved in Immune Cell Infiltration and Tumor Progression of Lung Adenocarcinoma. (PMID:36769082)
• CUL3 induces mitochondrial dysfunction via MRPL12 ubiquitination in renal tubular epithelial cells. (PMID:37526061)
• Mitochondrial ribosomal protein L12 potentiates hepatocellular carcinoma by regulating mitochondrial biogenesis and metabolic reprogramming. (PMID:38104924)
• The m6A Reader YTHDC2 Suppresses Lung Adenocarcinoma Tumorigenesis by Destabilizing MRPL12. (PMID:38129673)
• The role of lysine acetylation in the function of mitochondrial ribosomal protein L12. (PMID:38146092)
• Role of mitochondrial ribosomal protein L7/L12 (MRPL12) in diabetic ischemic heart disease. (PMID:38977138)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrpl12	ENSDARG00000038768
mus_musculus	Mrpl12	ENSMUSG00000039640
rattus_norvegicus	Mrpl12	ENSRNOG00000036695
drosophila_melanogaster	mRpL12	FBGN0011787
caenorhabditis_elegans		WBGENE00012361

Protein

Protein identifiers

Large ribosomal subunit protein bL12m — P52815 (reviewed: P52815)

Alternative names: 39S ribosomal protein L12, mitochondrial, 5c5-2

All UniProt accessions (1): P52815

UniProt curated annotations — full annotation on UniProt →

Function. As a component of the mitochondrial large ribosomal subunit, plays a role in mitochondrial translation. When present in mitochondria as a free protein not associated with the ribosome, associates with mitochondrial RNA polymerase POLRMT to activate transcription. Required for POLRMT stability.

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. bL12m interacts with NOA1.

Subcellular location. Mitochondrion matrix.

Post-translational modifications. Two mature forms are produced by differential two-step proteolytic cleavage. Cleaved by the mitochondrial processing protease to produce the long mature form and subsequently by the mitochondrial intermediate protease to produce the short mature form. In the presence of CUL3, undergoes ‘Lys-63’-linked ubiquitination at Lys-150 which results in proteasomal degradation.

Disease relevance. Combined oxidative phosphorylation deficiency 45 (COXPD45) [MIM:618951] An autosomal recessive mitochondrial disorder with onset in utero and characterized by poor overall growth, failure to thrive, global developmental delay, poor or absent speech, seizures, hypotonia, loss of walking, acute progressive neurologic deterioration, brain lesions, and facial dysmorphism. Laboratory studies show increased serum lactate and decreased mitochondrial respiratory chain enzyme activity in patient tissues. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. High-glucose conditions in renal tubular epithelial cells lead to up-regulation of CUL3 expression, significant increase in CUL3-mediated ubiquitination of MRPL12 and dysregulation of mitochondrial biosynthesis.

Similarity. Belongs to the bacterial ribosomal protein bL12 family.

RefSeq proteins (1): NP_002940* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000206	Ribosomal_bL12	Family
IPR008932	Ribosomal_bL12_oligo	Domain
IPR013823	Ribosomal_bL12_C	Domain
IPR014719	Ribosomal_bL12_C/ClpS-like	Homologous_superfamily
IPR036235	Ribosomal_bL12_oligo_N_sf	Homologous_superfamily

Pfam: PF00542, PF16320

UniProt features (28 total): modified residue 12, mutagenesis site 9, chain 2, sequence variant 2, transit peptide 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7QI4	ELECTRON MICROSCOPY	2.21
9OLF	ELECTRON MICROSCOPY	2.46
7PO4	ELECTRON MICROSCOPY	2.56
6ZM6	ELECTRON MICROSCOPY	2.59
7O9M	ELECTRON MICROSCOPY	2.6
9CN3	ELECTRON MICROSCOPY	2.62
7QI5	ELECTRON MICROSCOPY	2.63
9PR4	ELECTRON MICROSCOPY	2.77
9PRA	ELECTRON MICROSCOPY	2.83
8ANY	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
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
9UWH	ELECTRON MICROSCOPY	3
9PGI	ELECTRON MICROSCOPY	3.02
9PG8	ELECTRON MICROSCOPY	3.06
9PS7	ELECTRON MICROSCOPY	3.08
7PO2	ELECTRON MICROSCOPY	3.09
7O9K	ELECTRON MICROSCOPY	3.1
8OIR	ELECTRON MICROSCOPY	3.1
9PSI	ELECTRON MICROSCOPY	3.12
7L20	ELECTRON MICROSCOPY	3.15
9PGM	ELECTRON MICROSCOPY	3.18
9PRX	ELECTRON MICROSCOPY	3.23
9PS0	ELECTRON MICROSCOPY	3.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52815-F1	67.55	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (13): 163, 173, 178, 178, 185, 150, 125, 138, 142, 144, 150, 150, 162

Mutagenesis-validated functional residues (9):

Position	Phenotype
138	no effect on promoter binding activity of polrmt.
142	no effect on promoter binding activity of polrmt.
144	no effect on promoter binding activity of polrmt.
144	no effect on ubiquitination.
147	no effect on ubiquitination.
150	reduced ubiquitination.
163	no effect on promoter binding activity of polrmt.
173	no effect on promoter binding activity of polrmt.
173	reduced promoter binding activity of polrmt.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5368286	Mitochondrial translation initiation
R-HSA-5389840	Mitochondrial translation elongation
R-HSA-5419276	Mitochondrial translation termination
R-HSA-9837999	Mitochondrial protein degradation
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: 230 (showing top): BASSO_B_LYMPHOCYTE_NETWORK, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_TRANSLATION, TGACCTY_ERR1_Q2, MODULE_16, GOBP_TRANSLATION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, WHN_B, WONG_MITOCHONDRIA_GENE_MODULE, MODULE_18

GO Biological Process (4): mitochondrial transcription (GO:0006390), translation (GO:0006412), mitochondrial translation (GO:0032543), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), 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
Metabolism of proteins	2
Translation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
DNA-templated transcription	2
mitochondrial gene expression	2
mitochondrial RNA metabolic process	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
translation	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
RNA binding	1
structural molecule activity	1
ribosome	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	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

3098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL12	MRPL58	Q14197	949
MRPL12	POLRMT	O00411	924
MRPL12	NDUFB8	O95169	830
MRPL12	MRPS18B	Q9Y676	753
MRPL12	ADSL	P30566	751
MRPL12	MT-ATP6	P00846	748
MRPL12	MRPL11	Q9Y3B7	719
MRPL12	TEFM	Q96QE5	706
MRPL12	MRPS7	Q9Y2R9	693
MRPL12	MRPS16	Q9Y3D3	693
MRPL12	DAP3	P51398	686
MRPL12	MRPL44	Q9H9J2	677
MRPL12	MRPS22	P82650	657
MRPL12	MRPS34	P82930	648
MRPL12	MRPL17	Q9NRX2	645

IntAct

213 interactions, top by confidence:

A	B	Type	Score
MRPL12	POLRMT	psi-mi:“MI:0915”(physical association)	0.800
POLRMT	MRPL12	psi-mi:“MI:0914”(association)	0.800
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
SS18L2	SMARCA2	psi-mi:“MI:0914”(association)	0.570
NTM	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
FBLN1	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	NTM	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	EFCAB2	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
NBL1	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	EXOC3L2	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
TXNDC9	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	TRIM59	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	MAPRE3	psi-mi:“MI:0915”(physical association)	0.560
SAT1	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
	MRPL12	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	CBX3	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	MORF4L2	psi-mi:“MI:0915”(physical association)	0.560
MRPL12	SEPTIN1	psi-mi:“MI:0915”(physical association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550

BioGRID (527): MRPL12 (Affinity Capture-MS), MRPL12 (Affinity Capture-MS), MRPL12 (Affinity Capture-MS), MRPL12 (Affinity Capture-MS), MRPL12 (Affinity Capture-MS), MRPL12 (Affinity Capture-MS), MRPL12 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), SEPT10 (Affinity Capture-MS), FOXP2 (Affinity Capture-MS), SEPT3 (Affinity Capture-MS), SDR39U1 (Affinity Capture-MS), FOXP4 (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), GTPBP8 (Affinity Capture-MS)

ESM2 similar proteins: A0JN80, A1L2P7, A6QPQ5, B0UYI1, B2RYT9, B8BAI9, B9SEZ6, O02789, O57486, O75570, O95801, P09838, P27641, P36195, P42118, P43897, P52815, P82933, Q0P4D6, Q1L8I0, Q2KI15, Q3MHI7, Q4V7E5, Q58DQ5, Q5R5N8, Q5R952, Q5U2P0, Q5XF75, Q640B4, Q7SXA9, Q8BJU9, Q8C0S1, Q8CE96, Q8K0Z7, Q8K126, Q8R3H9, Q8TF46, Q8VI84, Q8WTT2, Q91Y26

Diamond homologs: A0R8H0, A0T0C0, A0T0Q7, A1B014, A1USC7, A2BNZ6, A2BUH8, A2C031, A3PAR9, A5IQ94, A5VR16, A6QEJ2, A6TZ17, A6X0A8, A7GK11, A7WYW4, A8EXK7, A8G2K8, A8GMA6, A8GV23, A8YZN8, A8ZV50, A9B5G8, A9ISF8, A9M5R1, B0CH42, B1GZ74, B2S2I7, B2S688, B3QC01, B4R8K4, B6JER8, B7HJ38, B7HQT4, B7IT09, B7JKA8, B8IS76, B9IZI4, B9KL82, C0RJL2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL12	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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	30	33.0×	1e-36
Mitochondrial translation initiation	31	31.5×	8e-37
Mitochondrial translation elongation	31	31.5×	8e-37
Mitochondrial ribosome-associated quality control	31	30.4×	1e-36
Mitochondrial translation termination	32	28.1×	1e-36
Translation	31	15.4×	1e-26

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	32	37.3×	2e-39
translation	18	12.4×	3e-12
negative regulation of translation	7	9.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	55
Likely benign	48
Benign	16

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
973971	NM_002949.4(MRPL12):c.542C>T (p.Ala181Val)	Pathogenic

SpliceAI

752 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81703573:CAGG:C	donor_loss	1.0000
17:81703574:AGG:A	donor_loss	1.0000
17:81703576:G:GA	donor_loss	1.0000
17:81704429:AGG:A	donor_loss	1.0000
17:81704630:CAGAA:C	acceptor_loss	1.0000
17:81704631:A:AC	acceptor_loss	1.0000
17:81704631:A:AG	acceptor_gain	1.0000
17:81704631:AGAAA:A	acceptor_loss	1.0000
17:81704632:G:GG	acceptor_gain	1.0000
17:81704632:G:GT	acceptor_gain	1.0000
17:81704632:G:T	acceptor_loss	1.0000
17:81704632:GA:G	acceptor_gain	1.0000
17:81704632:GAA:G	acceptor_gain	1.0000
17:81704632:GAAA:G	acceptor_gain	1.0000
17:81704713:GGAG:G	donor_gain	1.0000
17:81704714:GAG:G	donor_gain	1.0000
17:81704714:GAGG:G	donor_gain	1.0000
17:81704715:AGGT:A	donor_loss	1.0000
17:81704716:GGTG:G	donor_loss	1.0000
17:81704717:G:C	donor_loss	1.0000
17:81704717:GTG:G	donor_loss	1.0000
17:81704718:T:G	donor_loss	1.0000
17:81706895:T:A	acceptor_gain	1.0000
17:81706902:TAAG:T	acceptor_loss	1.0000
17:81706903:A:AG	acceptor_gain	1.0000
17:81706903:AAG:A	acceptor_gain	1.0000
17:81706903:AAGGC:A	acceptor_gain	1.0000
17:81706904:A:G	acceptor_gain	1.0000
17:81706904:AG:A	acceptor_gain	1.0000
17:81706904:AGGC:A	acceptor_gain	1.0000

AlphaMissense

1273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81704414:T:C	L82P	0.999
17:81706955:T:A	V132D	0.999
17:81707129:G:C	K162N	0.998
17:81707129:G:T	K162N	0.998
17:81707001:G:C	K147N	0.997
17:81707001:G:T	K147N	0.997
17:81707010:G:C	K150N	0.997
17:81707010:G:T	K150N	0.997
17:81704390:T:C	L74P	0.996
17:81704426:T:C	L86P	0.996
17:81707124:G:C	A161P	0.996
17:81704372:T:A	V68D	0.995
17:81704423:T:C	L85P	0.995
17:81706961:T:C	L134P	0.995
17:81707036:T:A	V159D	0.995
17:81707127:A:G	K162E	0.994
17:81704646:T:C	I92T	0.993
17:81704640:T:C	L90S	0.992
17:81707033:T:A	L158H	0.992
17:81707033:T:C	L158P	0.992
17:81704381:T:A	I71N	0.991
17:81706994:T:C	L145P	0.991
17:81706999:A:G	K147E	0.991
17:81707221:G:A	G193D	0.991
17:81704402:A:T	E78V	0.990
17:81704414:T:A	L82H	0.990
17:81707008:A:G	K150E	0.990
17:81707128:A:C	K162T	0.990
17:81706997:T:A	I146N	0.989
17:81707128:A:T	K162M	0.989

dbSNP variants (sampled 300 via entrez): RS1000096042 (17:81704897 T>G), RS1000864019 (17:81705146 G>A), RS1000981087 (17:81704083 C>T), RS1001092493 (17:81705945 G>A,C), RS1001680185 (17:81705743 G>A), RS1001858293 (17:81703575 G>A), RS1001920678 (17:81707654 C>T), RS1002032097 (17:81704533 T>C), RS1002098649 (17:81704839 G>A), RS1002161776 (17:81703770 GC>G), RS1002655424 (17:81706365 G>T), RS1002717390 (17:81706766 C>A,T), RS1002986521 (17:81702413 C>G,T), RS1003935929 (17:81702779 A>T), RS1004638680 (17:81703736 G>A)

Disease associations

OMIM: gene MIM:602375 | disease phenotypes: MIM:618951

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 45	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (1): combined oxidative phosphorylation deficiency 45 (MONDO:0033533)

Orphanet (0):

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000286	Epicanthus
HP:0000311	Round face
HP:0000369	Low-set ears
HP:0000470	Short neck
HP:0000666	Horizontal nystagmus
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001695	Cardiac arrest
HP:0002151	Increased circulating lactate concentration
HP:0002500	Abnormal cerebral white matter morphology
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0008936	Axial hypotonia
HP:0011923	Decreased activity of mitochondrial complex I

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004764_7	LDL cholesterol change in response to fenofibrate in statin-treated type 2 diabetes	2.000000e-07
GCST004765_30	Total cholesterol change in response to fenofibrate in statin-treated type 2 diabetes	3.000000e-07
GCST010002_133	Refractive error	2.000000e-50

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007804	LDL cholesterol change measurement
EFO:0007806	total cholesterol change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295780 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.93	Kd	116.6	nM	CHEMBL5653589
6.93	ED50	116.6	nM	CHEMBL5653589
5.11	Kd	7738	nM	CHEMBL3752910
5.11	ED50	7738	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148770: Binding affinity to human MRPL12 incubated for 45 mins by Kinobead based pull down assay	kd	0.1166	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148770: Binding affinity to human MRPL12 incubated for 45 mins by Kinobead based pull down assay	kd	7.7383	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
beauvericin	affects cotreatment, decreases expression	2
enniatins	affects cotreatment, decreases expression	2
Acetaminophen	affects cotreatment, decreases expression	2
Plant Extracts	affects cotreatment, decreases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, decreases methylation	2
Particulate Matter	increases abundance, decreases expression	2
bisphenol A	increases expression	1
deoxynivalenol	increases expression	1
quercitrin	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
aflatoxin G1	affects cotreatment, decreases expression	1
aflatoxin B2	decreases expression, affects cotreatment	1
aflatoxin G2	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
nivalenol	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
pyrimidifen	increases expression	1
ICG 001	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	affects expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118974	Binding	Binding affinity to MRPL12 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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