MRPL3

Summary

MRPL3 (mitochondrial ribosomal protein L3, HGNC:10379) is a protein-coding gene on chromosome 3q22.1, encoding Large ribosomal subunit protein uL3m (P09001). It is a selective cancer dependency (DepMap: 45.8% 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 L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q.

Source: NCBI Gene 11222 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined oxidative phosphorylation defect type 9 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 164 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 22
• Cancer dependency (DepMap): dependent in 45.8% of screened cell lines
• MANE Select transcript: NM_007208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10379
Approved symbol	MRPL3
Name	mitochondrial ribosomal protein L3
Location	3q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MRL3, uL3m
Ensembl gene	ENSG00000114686
Ensembl biotype	protein_coding
OMIM	607118
Entrez	11222

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264995, ENST00000425847, ENST00000506487, ENST00000506946, ENST00000507669, ENST00000510043, ENST00000510154, ENST00000510923, ENST00000511168, ENST00000512877, ENST00000908739, ENST00000908740, ENST00000908741, ENST00000925018

RefSeq mRNA: 1 — MANE Select: NM_007208 NM_007208

CCDS: CCDS3071

Canonical transcript exons

ENST00000264995 — 10 exons

Exon	Start	End
ENSE00000778237	131471171	131471279
ENSE00001193887	131487680	131487740
ENSE00001311927	131462212	131462875
ENSE00002022651	131502730	131502971
ENSE00003464684	131469696	131469773
ENSE00003509108	131489981	131490080
ENSE00003564005	131498179	131498277
ENSE00003583971	131501531	131501715
ENSE00003620177	131500430	131500521
ENSE00003629897	131468091	131468168

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.6646 / max 456.6671, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44595	55.1567	1821
44594	10.8707	1744
44593	3.1924	1368
44591	1.6646	847
44592	0.7802	468

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.13	gold quality
tibia	UBERON:0000979	98.69	gold quality
esophagus squamous epithelium	UBERON:0006920	98.66	gold quality
gingival epithelium	UBERON:0001949	98.58	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.48	gold quality
gingiva	UBERON:0001828	98.44	gold quality
corpus epididymis	UBERON:0004359	98.44	gold quality
caput epididymis	UBERON:0004358	98.32	gold quality
sperm	CL:0000019	98.25	gold quality
squamous epithelium	UBERON:0006914	98.17	gold quality
colonic mucosa	UBERON:0000317	98.08	gold quality
epithelium of esophagus	UBERON:0001976	98.01	gold quality
male germ cell	CL:0000015	97.81	gold quality
heart right ventricle	UBERON:0002080	97.73	gold quality
germinal epithelium of ovary	UBERON:0001304	97.72	gold quality
nephron tubule	UBERON:0001231	97.71	gold quality
palpebral conjunctiva	UBERON:0001812	97.69	gold quality
parietal pleura	UBERON:0002400	97.63	gold quality
tongue squamous epithelium	UBERON:0006919	97.62	gold quality
cauda epididymis	UBERON:0004360	97.60	gold quality
oral cavity	UBERON:0000167	97.52	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.41	gold quality
mammalian vulva	UBERON:0000997	97.33	gold quality
endometrium	UBERON:0001295	97.33	gold quality
choroid plexus epithelium	UBERON:0003911	97.33	gold quality
biceps brachii	UBERON:0001507	97.28	gold quality
epithelium of nasopharynx	UBERON:0001951	97.19	gold quality
pleura	UBERON:0000977	97.17	gold quality
islet of Langerhans	UBERON:0000006	97.14	gold quality
deltoid	UBERON:0001476	96.97	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	8.90
E-MTAB-9689	no	591.88
E-MTAB-7303	no	59.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting MRPL3, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-7852-3P	98.37	67.98	823
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6831-3P	97.49	69.29	505

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• the first mutation in large mitochondrial ribosomal protein MRPL3 in a family of four sibs with hypertrophic cardiomyopathy, psychomotor retardation, and multiple respiratory chain deficiency.(MRPL3) (PMID:21786366)
• Found MRPL3 S75N variant is probably a rare cause of Tourette syndrome/chronic tic phenotype in Chinese Han patients. (PMID:22507240)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrpl3	ENSDARG00000103318
mus_musculus	Mrpl3	ENSMUSG00000032563
rattus_norvegicus	Mrpl3	ENSRNOG00000012650
drosophila_melanogaster	mRpL3	FBGN0030686
caenorhabditis_elegans		WBGENE00016142

Protein

Protein identifiers

Large ribosomal subunit protein uL3m — P09001 (reviewed: P09001)

Alternative names: 39S ribosomal protein L3, mitochondrial

All UniProt accessions (6): P09001, D6RBQ5, D6RC14, E7ETU7, E9PF06, H0Y9G6

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.

Disease relevance. Combined oxidative phosphorylation deficiency 9 (COXPD9) [MIM:614582] A mitochondrial disease characterized by failure to thrive, poor feeding, hypertrophic cardiomyopathy, hepatomegaly, and psychomotor retardation. Death in infancy has been observed in some cases. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the universal ribosomal protein uL3 family.

RefSeq proteins (1): NP_009139* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000597	Ribosomal_uL3	Family
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR019926	Ribosomal_uL3_CS	Conserved_site
IPR019927	Ribosomal_uL3_bact_org	Family

Pfam: PF00297

UniProt features (34 total): strand 17, helix 9, turn 4, sequence variant 2, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

86 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
8QU1	ELECTRON MICROSCOPY	2.74
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09001-F1	87.20	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: 256 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BASSO_B_LYMPHOCYTE_NETWORK, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_TRANSLATION, MODULE_16, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, MARTINEZ_RB1_TARGETS_UP, SCHUHMACHER_MYC_TARGETS_UP, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GNF2_XRCC5, RHODES_CANCER_META_SIGNATURE

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

GO Molecular Function (2): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), 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
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
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
protein-containing complex	1

Protein interactions and networks

STRING

4623 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPL3	RPL3	P39023	823
MRPL3	L3MBTL1	Q9Y468	813
MRPL3	SCML2	Q9UQR0	769
MRPL3	PRTN3	P15637	580
MRPL3	CBX4	O00257	542
MRPL3	MRPL21	Q7Z2W9	521
MRPL3	MRPL9	Q9BYD2	515
MRPL3	BMI1	P35226	491
MRPL3	R4GMX3	R4GMX3	491
MRPL3	MRPS5	P82675	486
MRPL3	METTL15	A6NJ78	477
MRPL3	MRPL13	Q9BYD1	458
MRPL3	DCPS	Q96C86	448
MRPL3	ZNF207	O43670	436
MRPL3	GALM	Q96C23	433

IntAct

146 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
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
RPL18	NOP56	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
MRPS26	ERAL1	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
MRPL13	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPL27	MRPL33	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
MRPL58	MRPL3	psi-mi:“MI:0403”(colocalization)	0.460
MRPL58	MRPL3	psi-mi:“MI:0914”(association)	0.460
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
Bach1	SYNM	psi-mi:“MI:0914”(association)	0.350
Gpsm1	OARD1	psi-mi:“MI:0914”(association)	0.350
Nfya	NFYB	psi-mi:“MI:0914”(association)	0.350

BioGRID (253): MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL3 (Affinity Capture-MS), MRPL15 (Co-fractionation), MRPL3 (Co-fractionation), MRPL3 (Co-fractionation), MRPL3 (Co-fractionation), MRPL3 (Co-fractionation)

ESM2 similar proteins: A2C4Z2, A9BCP0, B6YSL3, B8GKD3, O15235, O26110, O35680, P09001, P12629, P18665, P25998, P29766, P31165, P31334, P32611, P38064, P49404, P49406, Q0ID12, Q0VC21, Q0W1Y9, Q1K8T6, Q29IK4, Q29RU1, Q3T0J3, Q3ZBX6, Q46IR6, Q5JDJ0, Q5M818, Q5R7L3, Q5R8M4, Q5ZKT8, Q6AZN4, Q6DGM3, Q7SCX7, Q7V9W9, Q7XYP4, Q93425, Q97BX7, Q99N93

Diamond homologs: A0L5X3, A1B027, A1TYJ7, A1USL4, A4G9T8, A4YSJ2, A5ELM7, A5GAW5, A5V602, A5VR06, A6T3K4, A6U859, A6X0B8, A7HWR1, A7IFY1, A8EZL6, A8F2E7, A8GPF0, A8GT69, A8GVB4, A8IAS6, A9H3R5, A9IJ01, A9IW27, A9M5Q0, A9W4Q1, B0BUR0, B0CH32, B0T2C2, B0UHW9, B1LWS6, B1Y8I7, B1ZLK4, B2S679, B3QBY0, B4R8L7, B5EFQ0, B6IRQ6, B6JET3, B7L0R1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPL3	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 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	38	46.7×	6e-54
Mitochondrial translation initiation	35	44.4×	8e-49
Mitochondrial translation elongation	35	44.4×	8e-49
Mitochondrial translation	32	44.0×	2e-44
Mitochondrial translation termination	35	38.4×	3e-46
Translation	35	21.7×	1e-36
Peptide chain elongation	10	12.7×	1e-07
Viral mRNA Translation	10	12.7×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	36	51.7×	4e-51
translation	28	23.8×	1e-28
cytoplasmic translation	10	15.3×	2e-07
regulation of alternative mRNA splicing, via spliceosome	6	12.1×	6e-04
negative regulation of translation	7	11.3×	3e-04
RNA processing	5	9.0×	9e-03
mRNA processing	9	5.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	68
Likely benign	43
Benign	22

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
489330	NM_007208.4(MRPL3):c.629+1G>A	Pathogenic
2444448	NM_007208.4(MRPL3):c.413_414del (p.Asn137_Cys138insTer)	Likely pathogenic
30643	NM_007208.4(MRPL3):c.950C>G (p.Pro317Arg)	Likely pathogenic
3067933	NM_007208.4(MRPL3):c.93-2A>C	Likely pathogenic

SpliceAI

1849 predictions. Top by Δscore:

Variant	Effect	Δscore
3:131462873:GACC:G	acceptor_loss	1.0000
3:131462876:C:CC	acceptor_gain	1.0000
3:131462876:CTG:C	acceptor_loss	1.0000
3:131468086:CTTA:C	donor_loss	1.0000
3:131468087:TTA:T	donor_loss	1.0000
3:131468088:TA:T	donor_loss	1.0000
3:131468089:A:AC	donor_gain	1.0000
3:131468090:C:CC	donor_gain	1.0000
3:131468166:CAC:C	acceptor_gain	1.0000
3:131468166:CACCT:C	acceptor_loss	1.0000
3:131468167:ACCT:A	acceptor_loss	1.0000
3:131468169:C:CA	acceptor_loss	1.0000
3:131468170:T:A	acceptor_loss	1.0000
3:131469689:CACTT:C	donor_loss	1.0000
3:131469690:ACTT:A	donor_loss	1.0000
3:131469691:CTTAC:C	donor_loss	1.0000
3:131469692:TTA:T	donor_loss	1.0000
3:131469693:TA:T	donor_loss	1.0000
3:131469694:A:AC	donor_gain	1.0000
3:131469694:A:C	donor_loss	1.0000
3:131469694:ACTTT:A	donor_gain	1.0000
3:131469695:C:CT	donor_gain	1.0000
3:131469695:CT:C	donor_gain	1.0000
3:131469695:CTT:C	donor_gain	1.0000
3:131469695:CTTT:C	donor_gain	1.0000
3:131469695:CTTTC:C	donor_gain	1.0000
3:131469769:ATATC:A	acceptor_gain	1.0000
3:131469770:TATC:T	acceptor_gain	1.0000
3:131469771:ATC:A	acceptor_gain	1.0000
3:131469772:TC:T	acceptor_gain	1.0000

AlphaMissense

2261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:131471264:A:C	F215L	0.996
3:131471264:A:T	F215L	0.996
3:131471266:A:G	F215L	0.996
3:131498261:A:T	V129D	0.994
3:131487687:C:G	A208P	0.992
3:131500434:A:G	L122P	0.992
3:131487692:A:T	V206D	0.990
3:131487716:A:G	F198S	0.990
3:131471246:T:A	R221S	0.989
3:131471246:T:G	R221S	0.989
3:131500511:T:A	R96S	0.989
3:131500511:T:G	R96S	0.989
3:131471237:A:C	F224L	0.988
3:131471237:A:T	F224L	0.988
3:131471239:A:G	F224L	0.988
3:131487698:A:T	V204E	0.988
3:131487725:G:T	A195D	0.988
3:131500512:C:G	R96T	0.988
3:131498266:A:C	C127W	0.987
3:131468131:A:T	V285E	0.986
3:131469727:C:A	G262V	0.985
3:131500434:A:T	L122H	0.985
3:131500497:G:T	A101D	0.985
3:131500512:C:A	R96I	0.985
3:131471196:C:G	R238T	0.984
3:131490030:T:A	K173N	0.984
3:131490030:T:G	K173N	0.984
3:131468113:C:T	G291E	0.983
3:131469727:C:T	G262E	0.983
3:131471196:C:A	R238M	0.983

dbSNP variants (sampled 300 via entrez): RS1000069244 (3:131497932 T>C), RS1000144034 (3:131474308 G>A), RS1000189566 (3:131464425 G>A), RS1000190029 (3:131484801 G>T), RS1000309256 (3:131485097 T>C), RS1000347017 (3:131497537 T>C,G), RS1000352639 (3:131490574 A>C), RS1000419880 (3:131467099 G>A,C), RS1000527319 (3:131483261 G>A), RS1000598148 (3:131472414 T>C), RS1000643315 (3:131483568 T>C), RS1000683168 (3:131495956 A>G), RS1000806244 (3:131465857 C>A,T), RS1000882296 (3:131485312 C>A,G), RS1000882704 (3:131495729 A>G)

Disease associations

OMIM: gene MIM:607118 | disease phenotypes: MIM:614582

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation defect type 9	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (1): combined oxidative phosphorylation defect type 9 (MONDO:0013811)

Orphanet (1): Combined oxidative phosphorylation defect type 9 (Orphanet:319509)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001263	Global developmental delay
HP:0001397	Hepatic steatosis
HP:0001508	Failure to thrive
HP:0001639	Hypertrophic cardiomyopathy
HP:0001655	Patent foramen ovale
HP:0001942	Metabolic acidosis
HP:0001970	Tubulointerstitial nephritis
HP:0001993	Ketoacidosis
HP:0002094	Dyspnea
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly
HP:0003348	Hyperalaninemia
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003819	Death in childhood
HP:0011968	Feeding difficulties
HP:0030948	Elevated gamma-glutamyltransferase level
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031962	Elevated serum anion gap
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0032653	Elevated lactate:pyruvate ratio

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_142	Body mass index	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Tretinoin	decreases expression	2
Copper Sulfate	decreases expression, increases expression	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	increases reaction, affects binding	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
azoxystrobin	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Ethanol	increases abundance, affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Gold	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1

Clinical trials (associated diseases)

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