MRPS14

Summary

MRPS14 (mitochondrial ribosomal protein S14, HGNC:14049) is a protein-coding gene on chromosome 1q25.1, encoding Small ribosomal subunit protein uS14m (O60783). It is a selective cancer dependency (DepMap: 68.2% 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 that belongs to the ribosomal protein S14P family. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 63931 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined oxidative phosphorylation deficiency 38 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 57 total — 2 pathogenic
• Phenotypes (HPO): 22
• Cancer dependency (DepMap): dependent in 68.2% of screened cell lines
• MANE Select transcript: NM_022100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14049
Approved symbol	MRPS14
Name	mitochondrial ribosomal protein S14
Location	1q25.1
Locus type	gene with protein product
Status	Approved
Aliases	HSMRPS14, uS14m
Ensembl gene	ENSG00000120333
Ensembl biotype	protein_coding
OMIM	611978
Entrez	63931

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000367677, ENST00000476371, ENST00000498253, ENST00000881843, ENST00000915397

RefSeq mRNA: 1 — MANE Select: NM_022100 NM_022100

CCDS: CCDS1316

Canonical transcript exons

ENST00000476371 — 3 exons

Exon	Start	End
ENSE00001445354	175023364	175023425
ENSE00001928201	175012958	175014851
ENSE00003551304	175018418	175018576

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 95.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.6284 / max 448.9475, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15986	41.1725	1813
15985	0.4559	221

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	95.64	gold quality
endothelial cell	CL:0000115	94.38	gold quality
oocyte	CL:0000023	92.83	gold quality
secondary oocyte	CL:0000655	92.80	gold quality
triceps brachii	UBERON:0001509	92.64	gold quality
medial globus pallidus	UBERON:0002477	92.19	gold quality
parotid gland	UBERON:0001831	92.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.87	gold quality
islet of Langerhans	UBERON:0000006	91.73	gold quality
heart right ventricle	UBERON:0002080	91.59	gold quality
tendon	UBERON:0000043	91.48	gold quality
gluteal muscle	UBERON:0002000	91.37	gold quality
parietal pleura	UBERON:0002400	91.32	gold quality
periodontal ligament	UBERON:0008266	91.18	gold quality
mucosa of transverse colon	UBERON:0004991	90.89	gold quality
esophagus squamous epithelium	UBERON:0006920	90.75	gold quality
spinal cord	UBERON:0002240	90.57	gold quality
deltoid	UBERON:0001476	90.50	gold quality
adrenal tissue	UBERON:0018303	90.49	gold quality
pleura	UBERON:0000977	90.27	gold quality
pancreatic ductal cell	CL:0002079	90.19	gold quality
right adrenal gland	UBERON:0001233	89.99	gold quality
colonic epithelium	UBERON:0000397	89.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.82	gold quality
right adrenal gland cortex	UBERON:0035827	89.76	gold quality
calcaneal tendon	UBERON:0003701	89.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.60	gold quality
epithelium of esophagus	UBERON:0001976	89.59	gold quality
pancreas	UBERON:0001264	89.57	gold quality
left adrenal gland	UBERON:0001234	89.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting MRPS14, 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-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
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-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4677-5P	99.70	70.09	1940

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 68.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• our data demonstrate pathogenic mutations in MRPS14 can manifest as a perinatal-onset mitochondrial hypertrophic cardiomyopathy with a novel molecular pathogenic mechanism that impairs the function of mitochondrial ribosomes during translation elongation or mitochondrial mRNA recruitment rather than assembly. (PMID:30358850)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrps14	ENSDARG00000068305
mus_musculus	Mrps14	ENSMUSG00000058267
rattus_norvegicus	Mrps14	ENSRNOG00000079901
drosophila_melanogaster	mRpS14	FBGN0044030
caenorhabditis_elegans		WBGENE00011334

Protein

Protein identifiers

Small ribosomal subunit protein uS14m — O60783 (reviewed: O60783)

Alternative names: 28S ribosomal protein S14, mitochondrial

All UniProt accessions (2): O60783, F2Z361

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. Interacts with LIAT1.

Subcellular location. Mitochondrion.

Disease relevance. Combined oxidative phosphorylation deficiency 38 (COXPD38) [MIM:618378] An autosomal recessive disorder due to mitochondrial dysfunction and characterized by perinatal hypertrophic cardiomyopathy, growth retardation, muscle hypotonia, elevated lactate, dysmorphy and intellectual disability. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the universal ribosomal protein uS14 family.

RefSeq proteins (1): NP_071383* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001209	Ribosomal_uS14	Family

Pfam: PF00253

UniProt features (13 total): helix 6, strand 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-O60783-F1	87.18	0.79

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: 184 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, LAIHO_COLORECTAL_CANCER_SERRATED_UP, OSMAN_BLADDER_CANCER_DN, GOCC_RIBOSOME, GOCC_SMALL_RIBOSOMAL_SUBUNIT, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE, SANSOM_APC_TARGETS, GOCC_RIBOSOMAL_SUBUNIT

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

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

GO Cellular Component (8): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial ribosome (GO:0005761), mitochondrial small ribosomal subunit (GO:0005763), nuclear membrane (GO:0031965), cytoplasm (GO:0005737), 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
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organellar ribosome	1
mitochondrial matrix	1
organellar small ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
nucleus	1
nuclear envelope	1
organelle membrane	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

3257 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRPS14	MRPL44	Q9H9J2	687
MRPS14	MRPS25	P82663	665
MRPS14	MRPL24	Q96A35	644
MRPS14	MRPS18C	Q9Y3D5	640
MRPS14	MRPS27	Q92552	632
MRPS14	MRPS11	P82912	617
MRPS14	MRPS2	Q9Y399	615
MRPS14	MRPS9	P82933	607
MRPS14	MRPS10	P82664	604
MRPS14	MRPS7	Q9Y2R9	599
MRPS14	MRPL21	Q7Z2W9	594
MRPS14	MRPS18A	Q9NVS2	586
MRPS14	MRPL55	Q7Z7F7	577
MRPS14	OASL	Q15646	568
MRPS14	ZNF707	Q96C28	567

IntAct

158 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ERBB3	PIK3R2	psi-mi:“MI:0914”(association)	0.700
MRPS27	MRPS14	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
MRPS14	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
MRPS14	GSN	psi-mi:“MI:0915”(physical association)	0.560
MRPS14		psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	MRPS14	psi-mi:“MI:0915”(physical association)	0.560
MRPS15	MRPS14	psi-mi:“MI:0914”(association)	0.530
RPL6	MRPS14	psi-mi:“MI:0914”(association)	0.530
TRMT10B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPS18B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPS18C	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MRPS34	MRPS12	psi-mi:“MI:0914”(association)	0.530
MRPS11	MRPS14	psi-mi:“MI:0914”(association)	0.530

BioGRID (275): MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Co-fractionation), RPS2 (Co-fractionation), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS14 (Affinity Capture-MS)

ESM2 similar proteins: A0AJY7, B1VKG7, O60783, P56556, P82915, P82920, P82933, Q02366, Q0MQA3, Q0MQA4, Q0MQA5, Q0VFH6, Q13084, Q19V89, Q1JQ99, Q29IK4, Q2HJJ1, Q2TA12, Q2TBR2, Q3T040, Q3T0J3, Q498T4, Q58DQ5, Q58DV5, Q5I0K8, Q5T653, Q5U4Z8, Q5ZMU0, Q6B860, Q6DDY9, Q6P1L8, Q71YD4, Q7M0E7, Q7SF85, Q7ZUH5, Q80X85, Q8MFA1, Q8Y620, Q92AC7, Q9BYC9

Diamond homologs: A0AJY7, A0M585, A1B040, A1TYL0, A3PGM4, A4WVJ5, A4X8U4, A5FN08, A5ISL8, A5UDT4, A5UHU4, A5VQZ3, A5WCK3, A6GZ86, A6KYI2, A6QGN8, A6U1F6, A6X0D1, A7HWS4, A7X1Z0, A7Z2Q4, A8FI98, A8M6L1, A9IHT7, A9M5N7, B0B913, B0BAP2, B0CH19, B0U5L2, B0UX27, B2I8I2, B2S666, B3CN39, B4R8N0, B6IRR9, O31587, O60783, O84792, P05716, P14875

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MRPS14	“form complex”	“28S mitochondrial small 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	21	24.3×	8e-22
Mitochondrial translation initiation	22	23.5×	3e-22
Mitochondrial translation elongation	22	23.5×	3e-22
Mitochondrial ribosome-associated quality control	22	22.7×	4e-22
Mitochondrial translation termination	22	20.3×	4e-21
Translation	24	12.5×	5e-18
Peptide chain elongation	9	9.6×	1e-05
Viral mRNA Translation	9	9.6×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	22	25.8×	2e-22
translation	20	13.9×	7e-15
cytoplasmic translation	10	12.5×	2e-06
mRNA stabilization	5	12.4×	4e-03
negative regulation of translation	8	10.6×	2e-04
regulation of alternative mRNA splicing, via spliceosome	6	9.9×	3e-03
RNA processing	6	8.9×	4e-03
mRNA splicing, via spliceosome	10	6.2×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	39
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4688188	D37N	Pathogenic
4688189	MRPS14, ASN60ASP	Pathogenic

SpliceAI

274 predictions. Top by Δscore:

Variant	Effect	Δscore
1:175018403:T:C	donor_gain	1.0000
1:175018412:GCTAA:G	donor_loss	1.0000
1:175018413:CTAA:C	donor_loss	1.0000
1:175018414:TAA:T	donor_loss	1.0000
1:175018415:AACC:A	donor_loss	1.0000
1:175018416:ACCTG:A	donor_loss	1.0000
1:175018447:T:A	donor_gain	1.0000
1:175018447:T:TA	donor_loss	1.0000
1:175018467:AG:A	donor_gain	1.0000
1:175018467:AGC:A	donor_gain	1.0000
1:175018468:G:C	donor_gain	1.0000
1:175018476:T:C	donor_gain	1.0000
1:175018573:CCAT:C	acceptor_gain	1.0000
1:175018574:CAT:C	acceptor_gain	1.0000
1:175018574:CATC:C	acceptor_gain	1.0000
1:175018576:TC:T	acceptor_loss	1.0000
1:175018577:CTGAA:C	acceptor_loss	1.0000
1:175018578:T:G	acceptor_loss	1.0000
1:175014848:CATC:C	acceptor_gain	0.9900
1:175018448:C:A	donor_gain	0.9900
1:175018467:A:AC	donor_gain	0.9900
1:175018467:AGCCT:A	donor_gain	0.9900
1:175018572:ACCAT:A	acceptor_gain	0.9900
1:175018573:CCATC:C	acceptor_gain	0.9900
1:175018575:AT:A	acceptor_gain	0.9900
1:175018577:C:CC	acceptor_gain	0.9900
1:175023358:CCTGA:C	donor_loss	0.9700
1:175023359:CTGAC:C	donor_loss	0.9700
1:175023360:TGA:T	donor_loss	0.9700
1:175023361:GAC:G	donor_loss	0.9700

AlphaMissense

822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:175014735:A:C	S107R	0.992
1:175014735:A:T	S107R	0.992
1:175014737:T:G	S107R	0.992
1:175014810:G:C	S82R	0.992
1:175014810:G:T	S82R	0.992
1:175014812:T:G	S82R	0.992
1:175018500:C:G	R41P	0.991
1:175014674:A:G	W128R	0.990
1:175014674:A:T	W128R	0.990
1:175014736:C:A	S107I	0.990
1:175014844:G:T	A71D	0.990
1:175018469:C:A	R51S	0.989
1:175018469:C:G	R51S	0.989
1:175014746:A:G	W104R	0.988
1:175014746:A:T	W104R	0.988
1:175014712:G:T	A115D	0.987
1:175018448:C:A	R58S	0.987
1:175018448:C:G	R58S	0.987
1:175014691:C:T	G122E	0.984
1:175018513:C:G	D37H	0.984
1:175018515:C:G	R36P	0.984
1:175014785:A:G	C91R	0.983
1:175018449:C:G	R58T	0.983
1:175014772:G:A	S95F	0.981
1:175018456:A:G	S56P	0.981
1:175014672:C:A	W128C	0.980
1:175014672:C:G	W128C	0.980
1:175018464:C:G	R53P	0.980
1:175014713:C:G	A115P	0.979
1:175018502:T:A	R40S	0.978

dbSNP variants (sampled 300 via entrez): RS1000049825 (1:175012653 A>G), RS1000660074 (1:175019913 G>T), RS1000692402 (1:175024276 A>C), RS1000933412 (1:175013435 T>TAATC), RS1001201278 (1:175025065 A>G), RS1001834497 (1:175018326 T>C), RS1002876432 (1:175023589 C>A), RS1003101377 (1:175016958 G>A), RS1003117325 (1:175016738 T>C,G), RS1003212673 (1:175021817 T>C), RS1003221601 (1:175021944 T>A), RS1003563031 (1:175016786 G>A), RS1003854129 (1:175015420 C>T), RS1003947697 (1:175016694 G>T), RS1003999978 (1:175016239 G>A,T)

Disease associations

OMIM: gene MIM:611978 | disease phenotypes: MIM:618378

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 38	Moderate	Autosomal recessive

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 38 (MONDO:0032712)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000316	Hypertelorism
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000750	Delayed speech and language development
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001508	Failure to thrive
HP:0001639	Hypertrophic cardiomyopathy
HP:0001716	Wolff-Parkinson-White syndrome
HP:0002093	Respiratory insufficiency
HP:0002151	Increased circulating lactate concentration
HP:0003128	Lactic acidosis
HP:0003348	Hyperalaninemia
HP:0005280	Depressed nasal bridge
HP:0008322	Abnormal mitochondrial morphology
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0011800	Midface retrusion
HP:0011923	Decreased activity of mitochondrial complex I
HP:0011924	Decreased activity of mitochondrial complex III
HP:0011925	Decreased activity of mitochondrial ATP synthase complex
HP:0031936	Delayed ability to walk

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010988_261	Adult body size	8.000000e-10
GCST90002400_527	Plateletcrit	7.000000e-09
GCST90013442_2	Keratoconus	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	decreases expression, affects cotreatment	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	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Cadmium	increases expression	1
Carbamazepine	affects expression	1
Citrinin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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