MRPL49

Summary

MRPL49 (mitochondrial ribosomal protein L49, HGNC:1176) is a protein-coding gene on chromosome 11q13.1, encoding Large ribosomal subunit protein mL49 (Q13405). It is a selective cancer dependency (DepMap: 81.5% 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. Pseudogenes corresponding to this gene are found on chromosomes 5q and 8p.

Source: NCBI Gene 740 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Strong, GenCC)
• Clinical variants (ClinVar): 44 total — 5 pathogenic
• Cancer dependency (DepMap): dependent in 81.5% of screened cell lines
• MANE Select transcript: NM_004927

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1176
Approved symbol	MRPL49
Name	mitochondrial ribosomal protein L49
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	NOF, NOF1, L49mt, mL49
Ensembl gene	ENSG00000149792
Ensembl biotype	protein_coding
OMIM	606866
Entrez	740

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000279242, ENST00000524482, ENST00000526171, ENST00000526319, ENST00000528529, ENST00000531705, ENST00000532671, ENST00000533943, ENST00000534078, ENST00000904843, ENST00000904844, ENST00000918905

RefSeq mRNA: 1 — MANE Select: NM_004927 NM_004927

CCDS: CCDS8096

Canonical transcript exons

ENST00000279242 — 4 exons

Exon	Start	End
ENSE00002148032	65125726	65127371
ENSE00002166229	65122321	65122424
ENSE00003623696	65124502	65124652
ENSE00003663906	65125488	65125612

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.0771 / max 197.3439, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115029	47.9534	1820
115028	2.1236	1092

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	97.06	gold quality
right adrenal gland	UBERON:0001233	96.88	gold quality
pancreatic ductal cell	CL:0002079	96.43	gold quality
left adrenal gland	UBERON:0001234	96.35	gold quality
left adrenal gland cortex	UBERON:0035825	96.19	gold quality
adrenal cortex	UBERON:0001235	96.18	gold quality
ileal mucosa	UBERON:0000331	96.00	gold quality
endometrium epithelium	UBERON:0004811	95.94	gold quality
adrenal gland	UBERON:0002369	95.83	gold quality
tongue squamous epithelium	UBERON:0006919	95.49	gold quality
middle temporal gyrus	UBERON:0002771	94.84	gold quality
type B pancreatic cell	CL:0000169	94.58	gold quality
epithelium of bronchus	UBERON:0002031	94.38	gold quality
renal glomerulus	UBERON:0000074	94.34	gold quality
islet of Langerhans	UBERON:0000006	94.30	gold quality
metanephric glomerulus	UBERON:0004736	94.15	gold quality
adult mammalian kidney	UBERON:0000082	94.13	gold quality
bronchus	UBERON:0002185	94.12	gold quality
kidney epithelium	UBERON:0004819	93.82	gold quality
olfactory bulb	UBERON:0002264	93.77	silver quality
bronchial epithelial cell	CL:0002328	93.76	gold quality
metanephros	UBERON:0000081	93.63	gold quality
corpus epididymis	UBERON:0004359	93.56	gold quality
nephron tubule	UBERON:0001231	93.49	gold quality
palpebral conjunctiva	UBERON:0001812	93.38	gold quality
upper leg skin	UBERON:0004262	93.30	gold quality
kidney	UBERON:0002113	93.03	gold quality
tibialis anterior	UBERON:0001385	92.99	gold quality
cortex of kidney	UBERON:0001225	92.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.43
E-GEOD-93593	yes	7.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, NCOR1

miRNA regulators (miRDB)

68 targeting MRPL49, 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-371B-5P	99.99	75.34	4759
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6503-5P	99.62	66.96	597

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 81.5% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	MRPL49	ENSDARG00000075422
mus_musculus	Mrpl49	ENSMUSG00000007338
rattus_norvegicus	Mrpl49	ENSRNOG00000020975
drosophila_melanogaster	mRpL49	FBGN0030433
caenorhabditis_elegans		WBGENE00011247

Protein

Protein identifiers

Large ribosomal subunit protein mL49 — Q13405 (reviewed: Q13405)

Alternative names: 39S ribosomal protein L49, mitochondrial, Neighbor of FAU, Protein NOF1

All UniProt accessions (5): Q13405, E9PI78, E9PNF1, E9PRD2, H0YDP7

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. Interacts with OXA1L.

Subcellular location. Mitochondrion.

Tissue specificity. Ubiquitous.

Disease relevance. Combined oxidative phosphorylation deficiency 60 (COXPD60) [MIM:621195] An autosomal recessive mitochondrial disease characterized by diverse clinical manifestations encompassing bilateral sensorineural hearing loss and primary ovarian insufficiency, microcephaly, learning disability, developmental delay, leukodystrophy, and retinal disease. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mL49 family.

RefSeq proteins (1): NP_004918* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007740	Ribosomal_mL49	Family

Pfam: PF05046

UniProt features (20 total): strand 8, sequence variant 4, turn 3, helix 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

85 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
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13405-F1	85.01	0.73

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: 169 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_MITOCHONDRIAL_TRANSLATION, GGGTGGRR_PAX4_03, chr11q13, SP1_Q2_01, GOBP_TRANSLATION, NKX62_Q2, YY1_02, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, E4F1_Q6, GOCC_MITOCHONDRIAL_ENVELOPE, CCCNNNNNNAAGWT_UNKNOWN, PU1_Q6, MAF_Q6, RFX1_02

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

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 ribosome (GO:0005761), 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
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	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 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

1520 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL49	MRPL51	Q4U2R6	692
MRPL49	MRPS22	P82650	624
MRPL49	MRPL48	Q96GC5	618
MRPL49	MRPL45	Q9BRJ2	616
MRPL49	MRPL20	Q9BYC9	559
MRPL49	MTRF1L	Q9UGC7	512
MRPL49	MRPL19	P49406	500
MRPL49	MRPL43	Q8N983	484
MRPL49	MRPS18B	Q9Y676	473
MRPL49	MRPL34	Q9BQ48	447
MRPL49	COA5	Q86WW8	438
MRPL49	OXA1L	Q15070	426
MRPL49	MRPL1	Q9BYD6	425
MRPL49	MRPL24	Q96A35	396
MRPL49	MRPL11	Q9Y3B7	393

IntAct

146 interactions, top by confidence:

A	B	Type	Score
MIS12	ZWINT	psi-mi:“MI:0914”(association)	0.900
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
MRPL37	HSPD1	psi-mi:“MI:0914”(association)	0.710
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
MRPL49	BDNF	psi-mi:“MI:0915”(physical association)	0.560
MRPL49	ATN1	psi-mi:“MI:0915”(physical association)	0.560
MRPL49	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
	MRPL49	psi-mi:“MI:0915”(physical association)	0.560
MRPL49	JPH3	psi-mi:“MI:0915”(physical association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
MRPL50	GTPBP10	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
MRPL41	MRPL3	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	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 (231): MRPL49 (Affinity Capture-RNA), MRPL49 (Affinity Capture-RNA), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS), MRPL49 (Reconstituted Complex), MRPL49 (Synthetic Lethality), MRPL49 (Affinity Capture-MS), MRPL49 (Affinity Capture-MS)

ESM2 similar proteins: A0JMH2, A0PJW6, A5PJW2, B3DI94, B5DFG1, O43677, P0CB69, P0CB70, Q059A4, Q0MQF5, Q0MQF6, Q0V9C9, Q0VCH8, Q13405, Q3SX05, Q3SZA2, Q3SZV6, Q3U6U5, Q4G012, Q4KLZ1, Q4KM93, Q4R5K7, Q4R5Q4, Q4VAE3, Q53S58, Q5EA71, Q5R8X0, Q5XIC2, Q66LN0, Q6DC58, Q6PI78, Q75CX4, Q80YU0, Q863F8, Q863G5, Q8BPE4, Q8BWM0, Q8N159, Q8R4H7, Q95SS8

Diamond homologs: P25642, Q10139, Q13405, Q4R5K7, Q5EA71, Q5R8X0, Q7S518, Q9CQ40, Q21939, Q9VYI3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL49	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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	33	41.4×	9e-44
Mitochondrial translation	29	40.7×	2e-38
Mitochondrial translation initiation	31	40.1×	7e-41
Mitochondrial translation elongation	31	40.1×	7e-41
Mitochondrial translation termination	31	34.7×	1e-38
Translation	32	20.3×	6e-32
Peptide chain elongation	7	9.1×	6e-04
Viral mRNA Translation	7	9.1×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	33	48.6×	3e-45
translation	25	21.8×	4e-24
cytoplasmic translation	8	12.6×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2691724	NM_004927.4(MRPL49):c.263G>A (p.Arg88His)	Pathogenic
2691726	NM_004927.4(MRPL49):c.125_126del (p.Val42fs)	Pathogenic
3897917	MRPL49, ARG88HIS (rs1565337413)	Pathogenic
4813537	NM_004927.4(MRPL49):c.463C>T (p.Gln155Ter)	Pathogenic
4813538	NM_004927.4(MRPL49):c.499_500insTT (p.Ter167PheextTer?)	Pathogenic

SpliceAI

539 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65125480:T:A	acceptor_gain	1.0000
11:65125482:TTGCA:T	acceptor_loss	1.0000
11:65125483:T:A	acceptor_gain	1.0000
11:65125483:TGCAG:T	acceptor_loss	1.0000
11:65125485:CAGA:C	acceptor_loss	1.0000
11:65125486:A:AG	acceptor_gain	1.0000
11:65125486:A:C	acceptor_loss	1.0000
11:65125487:G:GG	acceptor_gain	1.0000
11:65125487:GA:G	acceptor_gain	1.0000
11:65125487:GAC:G	acceptor_gain	1.0000
11:65125487:GACC:G	acceptor_gain	1.0000
11:65125487:GACCC:G	acceptor_gain	1.0000
11:65125592:A:T	donor_gain	1.0000
11:65125598:G:GT	donor_gain	1.0000
11:65125608:TCTGG:T	donor_gain	1.0000
11:65125610:TGG:T	donor_gain	1.0000
11:65125611:GG:G	donor_gain	1.0000
11:65125611:GGG:G	donor_gain	1.0000
11:65125612:GG:G	donor_gain	1.0000
11:65125612:GGTA:G	donor_loss	1.0000
11:65125613:G:GG	donor_gain	1.0000
11:65125613:GT:G	donor_loss	1.0000
11:65125614:TAAG:T	donor_loss	1.0000
11:65125721:CCCA:C	acceptor_loss	1.0000
11:65125724:A:AG	acceptor_gain	1.0000
11:65125724:A:G	acceptor_loss	1.0000
11:65125724:AG:A	acceptor_gain	1.0000
11:65125725:G:GA	acceptor_gain	1.0000
11:65125725:GG:G	acceptor_gain	1.0000
11:65125725:GGC:G	acceptor_gain	1.0000

AlphaMissense

1070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65125545:T:A	V96D	0.995
11:65125520:C:A	R88S	0.990
11:65125587:T:A	I110N	0.990
11:65125867:T:C	F166L	0.990
11:65125869:C:A	F166L	0.990
11:65125869:C:G	F166L	0.990
11:65124637:T:A	W72R	0.989
11:65124637:T:C	W72R	0.989
11:65125515:T:A	V86E	0.986
11:65125590:G:C	R111P	0.986
11:65125572:G:C	R105P	0.984
11:65125587:T:G	I110S	0.982
11:65125868:T:C	F166S	0.980
11:65124639:G:C	W72C	0.979
11:65124639:G:T	W72C	0.979
11:65125602:G:T	G115V	0.979
11:65125841:T:A	L157H	0.978
11:65125587:T:C	I110T	0.976
11:65125853:T:C	L161P	0.976
11:65125601:G:A	G115R	0.974
11:65125601:G:C	G115R	0.974
11:65125601:G:T	G115W	0.974
11:65125811:T:C	L147P	0.972
11:65125821:G:C	K150N	0.971
11:65125821:G:T	K150N	0.971
11:65125593:A:T	K112I	0.970
11:65125602:G:A	G115E	0.970
11:65125730:T:C	L120P	0.970
11:65125814:G:C	R148P	0.970
11:65125508:T:G	Y84D	0.969

dbSNP variants (sampled 300 via entrez): RS1000188824 (11:65122657 T>C), RS1001216092 (11:65122399 A>C), RS1001628612 (11:65123613 A>C), RS1002071969 (11:65123203 T>C), RS1003542760 (11:65123903 T>A), RS1003593745 (11:65124255 G>T), RS1003890450 (11:65127755 G>A,T), RS1005348183 (11:65122074 A>C), RS1005755142 (11:65124299 G>A), RS1005893173 (11:65126739 C>A,T), RS1005943218 (11:65123048 G>C), RS1006012356 (11:65124598 G>T), RS1007066733 (11:65127191 C>T), RS1007437925 (11:65123571 A>C), RS1007743492 (11:65122617 C>G,T)

Disease associations

OMIM: gene MIM:606866 | disease phenotypes: MIM:233400, MIM:621195, MIM:610498

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial disease	Strong	Autosomal recessive

Mondo (4): Perrault syndrome 1 (MONDO:0009300), mitochondrial disease (MONDO:0044970), combined oxidative phosphorylation deficiency 60 (MONDO:0978298), combined oxidative phosphorylation defect type 2 (MONDO:0012510)

Orphanet (4): Perrault syndrome (Orphanet:2855), Perrault syndrome type 1 (Orphanet:642945), Mitochondrial disease (Orphanet:68380), Combined oxidative phosphorylation defect type 2 (Orphanet:254920)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566468	Combined Oxidative Phosphorylation Deficiency 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Leflunomide	decreases expression	2
Benzo(a)pyrene	increases expression	2
Cisplatin	increases expression	2
Valproic Acid	decreases expression, increases methylation, affects expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
bisphenol A	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	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
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Arsenic Trioxide	decreases response to substance	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Dimethylnitrosamine	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Quercetin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	EARLY_PHASE1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies