MRPS25

Summary

MRPS25 (mitochondrial ribosomal protein S25, HGNC:14511) is a protein-coding gene on chromosome 3p25.1, encoding Small ribosomal subunit protein mS25 (P82663). It is a selective cancer dependency (DepMap: 52.2% 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. A pseudogene corresponding to this gene is found on chromosome 4. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 64432 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Limited, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• Phenotypes (HPO): 18
• Cancer dependency (DepMap): dependent in 52.2% of screened cell lines
• MANE Select transcript: NM_022497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14511
Approved symbol	MRPS25
Name	mitochondrial ribosomal protein S25
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Aliases	MRP-S25, FLJ00023, DKFZp313H0817, RPMS25, mS25
Ensembl gene	ENSG00000131368
Ensembl biotype	protein_coding
OMIM	611987
Entrez	64432

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 26 nonsense_mediated_decay, 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000253686, ENST00000420267, ENST00000444840, ENST00000447299, ENST00000449354, ENST00000474866, ENST00000496484, ENST00000695322, ENST00000695323, ENST00000695334, ENST00000695375, ENST00000695376, ENST00000695377, ENST00000695378, ENST00000695379, ENST00000695380, ENST00000695381, ENST00000695382, ENST00000695383, ENST00000695385, ENST00000695386, ENST00000695387, ENST00000695390, ENST00000695391, ENST00000695392, ENST00000695393, ENST00000695394, ENST00000695396, ENST00000698780, ENST00000698781, ENST00000698782, ENST00000698783, ENST00000887322, ENST00000887323, ENST00000939927

RefSeq mRNA: 1 — MANE Select: NM_022497 NM_022497

CCDS: CCDS2622

Canonical transcript exons

ENST00000253686 — 4 exons

Exon	Start	End
ENSE00000901292	15059369	15059475
ENSE00003963593	15053380	15053467
ENSE00003963595	15048512	15052633
ENSE00003963606	15065061	15065315

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.6611 / max 339.1804, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41240	42.5981	1823
41239	0.0630	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.61	gold quality
pancreatic ductal cell	CL:0002079	97.76	gold quality
right lobe of thyroid gland	UBERON:0001119	97.71	gold quality
left ventricle myocardium	UBERON:0006566	97.56	gold quality
left lobe of thyroid gland	UBERON:0001120	97.53	gold quality
heart left ventricle	UBERON:0002084	97.16	gold quality
cerebellar hemisphere	UBERON:0002245	97.13	gold quality
cardiac ventricle	UBERON:0002082	97.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.07	gold quality
cerebellar cortex	UBERON:0002129	96.98	gold quality
thyroid gland	UBERON:0002046	96.85	gold quality
adenohypophysis	UBERON:0002196	96.60	gold quality
gastrocnemius	UBERON:0001388	96.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.49	gold quality
cerebellum	UBERON:0002037	96.41	gold quality
right atrium auricular region	UBERON:0006631	96.33	gold quality
cardiac atrium	UBERON:0002081	96.25	gold quality
muscle of leg	UBERON:0001383	96.12	gold quality
myocardium	UBERON:0002349	96.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.07	gold quality
mucosa of transverse colon	UBERON:0004991	96.01	gold quality
transverse colon	UBERON:0001157	95.94	gold quality
heart	UBERON:0000948	95.84	gold quality
lower esophagus mucosa	UBERON:0035834	95.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.79	gold quality
metanephros cortex	UBERON:0010533	95.75	gold quality
right lobe of liver	UBERON:0001114	95.68	gold quality
lower esophagus	UBERON:0013473	95.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.58	gold quality
right uterine tube	UBERON:0001302	95.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.44
E-CURD-88	yes	3.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

103 targeting MRPS25, 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-4776-3P	100.00	68.73	1340
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4713-5P	99.78	67.80	1794

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 52.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• our data demonstrate the pathogenicity of the p.P72L variant and identify MRPS25 mutations as a new cause of mitochondrial translation defect. (PMID:31039582)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrps25	ENSDARG00000041306
mus_musculus	Mrps25	ENSMUSG00000014551
rattus_norvegicus	Mrps25	ENSRNOG00000010912
drosophila_melanogaster	mRpS25	FBGN0030572
caenorhabditis_elegans		WBGENE00021920

Protein

Protein identifiers

Small ribosomal subunit protein mS25 — P82663 (reviewed: P82663)

Alternative names: 28S ribosomal protein S25, mitochondrial

All UniProt accessions (9): A0A8Q3SHT9, A0A8Q3SHU8, A0A8Q3WKE1, A0A8Q3WKE3, A0A8Q3WKH6, A0A8Q3WKJ5, A0A8Q3WLJ1, E7EPW2, P82663

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.

Disease relevance. Combined oxidative phosphorylation deficiency 50 (COXPD50) [MIM:619025] An autosomal recessive, mitochondrial encephalomyopathy characterized by intrauterine growth retardation, poor overall growth, delayed psychomotor development, hypotonia, muscle weakness, progressive loss of ambulation, and mitochondrial oxidative phosphorylation deficiency in patient tissues. Brain imaging shows partial agenesis of the corpus callosum. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mS25 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P82663-1	1	yes
P82663-2	2
P82663-3	3

RefSeq proteins (1): NP_071942* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007741	Ribosomal_mL43/mS25/NADH_DH	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR040049	Ribosomal_mS25/mL61	Family

Pfam: PF05047

UniProt features (23 total): helix 10, strand 6, splice variant 3, turn 2, chain 1, sequence variant 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-P82663-F1	92.54	0.87

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: 163 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, CAATGCA_MIR33, GOCC_MITOCHONDRIAL_ENVELOPE, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, BERENJENO_TRANSFORMED_BY_RHOA_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, OSMAN_BLADDER_CANCER_DN, GOCC_RIBOSOME

GO Biological Process (1): mitochondrial translation (GO:0032543)

GO Molecular Function (1): structural constituent of ribosome (GO:0003735)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial small ribosomal subunit (GO:0005763), 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
structural molecule activity	1
ribosome	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organellar small ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPS25	MRPS14	O60783	665
MRPS25	MRPL44	Q9H9J2	641
MRPS25	MRPS2	Q9Y399	627
MRPS25	MRPL51	Q4U2R6	624
MRPS25	MRPS27	Q92552	614
MRPS25	MRPS5	P82675	608
MRPS25	MRPL45	Q9BRJ2	563
MRPS25	MRPS7	Q9Y2R9	537
MRPS25	MRPL18	Q9H0U6	523
MRPS25	MRPL55	Q7Z7F7	510
MRPS25	MRPS22	P82650	447
MRPS25	MRPS23	Q9Y3D9	444
MRPS25	MRPS11	P82912	414
MRPS25	MRPL54	Q6P161	403
MRPS25	MRPS18B	Q9Y676	397

IntAct

133 interactions, top by confidence:

A	B	Type	Score
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ERBB3	PIK3R2	psi-mi:“MI:0914”(association)	0.700
rep	MPHOSPH10	psi-mi:“MI:0914”(association)	0.660
MRPS27	MRPS14	psi-mi:“MI:0914”(association)	0.640
SDHAF3	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
FAM120A	SYNCRIP	psi-mi:“MI:0914”(association)	0.640
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
MRPS15	MRPS14	psi-mi:“MI:0914”(association)	0.530
TRMT10B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPS26	ERAL1	psi-mi:“MI:0914”(association)	0.530
MRPS18B	MRPS14	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPS11	MRPS14	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	psi-mi:“MI:0914”(association)	0.530
RPL7A	NVL	psi-mi:“MI:0914”(association)	0.530
MCM8	MRPS25	psi-mi:“MI:0915”(physical association)	0.400
Brwd3	WDR91	psi-mi:“MI:0914”(association)	0.350
Med22	MED7	psi-mi:“MI:0914”(association)	0.350
ZFC3H1	UNC119B	psi-mi:“MI:0914”(association)	0.350

BioGRID (332): MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS), MRPS25 (Affinity Capture-MS)

ESM2 similar proteins: A1D3P4, A3M0D8, A5DAI1, A5DSF0, A6ZN18, A7SG48, A7TML0, B0XPV4, C6Y4D2, H9IWW7, O14006, O43007, O94689, P14908, P19956, P25642, P32388, P32843, P36521, P38120, P62506, P62507, P82663, P82669, P87250, Q06090, Q2UBI2, Q4QR80, Q4WJ38, Q54D99, Q59ZY9, Q5A3J1, Q5A6Q4, Q5YLB4, Q6BPT6, Q6CTB6, Q6FIK2, Q6FL25, Q6FWV2, Q751P7

Diamond homologs: P82663, P82669, Q4QR80, Q9D125, Q9N361, Q9VY28

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPS25	“form complex”	“28S mitochondrial small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 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	16	18.9×	8e-14
Mitochondrial translation initiation	15	18.3×	4e-13
Mitochondrial translation elongation	15	18.3×	4e-13
Mitochondrial translation	13	17.2×	5e-11
Mitochondrial translation termination	15	15.8×	3e-12
Translation	17	10.2×	6e-11

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	16	19.9×	9e-14
ribosomal small subunit biogenesis	7	11.4×	8e-04
translation	13	9.5×	5e-07
RNA processing	6	9.4×	8e-03
protein import into nucleus	7	7.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
978474	NM_022497.5(MRPS25):c.215C>T (p.Pro72Leu)	Pathogenic

SpliceAI

3401 predictions. Top by Δscore:

Variant	Effect	Δscore
3:15013584:TATA:T	acceptor_loss	1.0000
3:15013585:ATAG:A	acceptor_loss	1.0000
3:15013586:TAGAT:T	acceptor_loss	1.0000
3:15013587:A:G	acceptor_loss	1.0000
3:15013588:G:GT	acceptor_loss	1.0000
3:15013588:GATT:G	acceptor_gain	1.0000
3:15016151:GATT:G	acceptor_gain	1.0000
3:15020748:TTCA:T	acceptor_loss	1.0000
3:15020749:TCA:T	acceptor_loss	1.0000
3:15020750:CA:C	acceptor_loss	1.0000
3:15020752:G:A	acceptor_loss	1.0000
3:15020752:GGCC:G	acceptor_gain	1.0000
3:15020928:GGAAT:G	donor_gain	1.0000
3:15020929:GAAT:G	donor_gain	1.0000
3:15020929:GAATG:G	donor_gain	1.0000
3:15020930:A:T	donor_gain	1.0000
3:15020930:AAT:A	donor_gain	1.0000
3:15020931:AT:A	donor_gain	1.0000
3:15020932:TG:T	donor_loss	1.0000
3:15020933:G:GG	donor_gain	1.0000
3:15020933:GTG:G	donor_loss	1.0000
3:15023191:T:TA	acceptor_gain	1.0000
3:15023197:A:AG	acceptor_gain	1.0000
3:15023197:AAGCT:A	acceptor_gain	1.0000
3:15023198:A:G	acceptor_gain	1.0000
3:15023199:G:GG	acceptor_gain	1.0000
3:15023199:GCT:G	acceptor_gain	1.0000
3:15023343:GCAAG:G	donor_gain	1.0000
3:15023344:CAAG:C	donor_loss	1.0000
3:15023345:AAGG:A	donor_loss	1.0000

AlphaMissense

1153 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:15065163:C:G	R11P	0.986
3:15052576:G:C	F129L	0.984
3:15052576:G:T	F129L	0.984
3:15052578:A:G	F129L	0.984
3:15065106:A:T	M30K	0.977
3:15065100:A:T	V32E	0.976
3:15059433:G:C	N59K	0.975
3:15059433:G:T	N59K	0.975
3:15065106:A:C	M30R	0.975
3:15065127:A:G	F23S	0.975
3:15052574:C:T	G130D	0.973
3:15059385:G:C	F75L	0.970
3:15059385:G:T	F75L	0.970
3:15059387:A:G	F75L	0.970
3:15065148:A:G	L16P	0.969
3:15065182:C:G	G5R	0.969
3:15065164:G:T	R11S	0.968
3:15059383:A:G	L76P	0.967
3:15065167:G:T	R10S	0.964
3:15052548:A:G	C139R	0.963
3:15065152:A:C	Y15D	0.963
3:15065115:A:T	V27E	0.961
3:15065160:G:A	T12I	0.960
3:15052518:A:G	C149R	0.959
3:15059460:G:C	F50L	0.959
3:15059460:G:T	F50L	0.959
3:15059462:A:G	F50L	0.959
3:15059455:A:T	I52K	0.958
3:15065174:G:C	F7L	0.957
3:15065174:G:T	F7L	0.957

dbSNP variants (sampled 300 via entrez): RS1000017575 (3:15042951 C>T), RS1000050366 (3:15058703 T>G), RS1000267875 (3:15063525 A>G), RS1000498217 (3:15044423 T>C), RS1000550003 (3:15051978 A>G), RS1000703991 (3:15045901 C>T), RS1000980446 (3:15058521 G>A,T), RS1001011629 (3:15058335 G>A,T), RS1001101837 (3:15065715 A>G), RS1001214972 (3:15049206 A>T), RS1001304150 (3:15064531 T>C), RS1001540747 (3:15061224 G>A,C), RS1001557016 (3:15055341 T>C), RS1001582473 (3:15049424 G>A), RS1001642582 (3:15055702 C>T)

Disease associations

OMIM: gene MIM:611987 | disease phenotypes: MIM:619025

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 50	Limited	Unknown
mitochondrial encephalomyopathy	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (2): combined oxidative phosphorylation deficiency 50 (MONDO:0033570), mitochondrial encephalomyopathy (MONDO:0004675)

Orphanet (0):

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000846	Adrenal insufficiency
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001338	Partial agenesis of the corpus callosum
HP:0001348	Brisk reflexes
HP:0001385	Hip dysplasia
HP:0001511	Intrauterine growth retardation
HP:0002015	Dysphagia
HP:0002421	Poor head control
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0007325	Generalized dystonia
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0031936	Delayed ability to walk
HP:0032989	Delayed ability to roll over
HP:0033128	Delayed ability to crawl

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_550	Femur bone mineral density x serum urate levels interaction	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017237	Mitochondrial Encephalomyopathies	C05.651.460.620; C10.228.140.163.540; C10.668.491.500.500; C18.452.132.540; C18.452.660.560.620

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	2
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Thiram	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Thapsigargin	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06213090	Not specified	RECRUITING	Patterns of Neurodevelopmental Disorders