MT-ND4

Summary

MT-ND4 (mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4, HGNC:7459) is a protein-coding gene on chromosome mitochondria, encoding Mitochondrial alternative ND4 protein (C0HME5). Regulates mitochondrial respiration by decreasing oxygen consumption.

Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Parkinson’s disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer’s disease.

Source: NCBI Gene 4538 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +5 more curated relationships
• Clinical variants (ClinVar): 151 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7459
Approved symbol	MT-ND4
Name	mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4
Location	mitochondria
Locus type	gene with protein product
Status	Approved
Aliases	ND4, NAD4
Ensembl gene	ENSG00000198886
Ensembl biotype	protein_coding
OMIM	516003
Entrez	4538

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361381

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000361381 — 1 exons

Exon	Start	End
ENSE00001666004	10760	12137

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 393.3408 / max 109905.1599, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194934	128.0952	1802
194933	120.7391	1798
194935	99.5925	1794
194936	44.9140	1746

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	100.00	gold quality
apex of heart	UBERON:0002098	100.00	gold quality
zone of skin	UBERON:0000014	99.99	gold quality
endocervix	UBERON:0000458	99.99	gold quality
adipose tissue	UBERON:0001013	99.99	gold quality
rectum	UBERON:0001052	99.99	gold quality
right lobe of liver	UBERON:0001114	99.99	gold quality
right lobe of thyroid gland	UBERON:0001119	99.99	gold quality
smooth muscle tissue	UBERON:0001135	99.99	gold quality
transverse colon	UBERON:0001157	99.99	gold quality
fundus of stomach	UBERON:0001160	99.99	gold quality
body of stomach	UBERON:0001161	99.99	gold quality
mucosa of stomach	UBERON:0001199	99.99	gold quality
cortex of kidney	UBERON:0001225	99.99	gold quality
right adrenal gland	UBERON:0001233	99.99	gold quality
left adrenal gland	UBERON:0001234	99.99	gold quality
left uterine tube	UBERON:0001303	99.99	gold quality
gastrocnemius	UBERON:0001388	99.99	gold quality
skin of abdomen	UBERON:0001416	99.99	gold quality
skin of leg	UBERON:0001511	99.99	gold quality
right coronary artery	UBERON:0001625	99.99	gold quality
temporal lobe	UBERON:0001871	99.99	gold quality
caudate nucleus	UBERON:0001873	99.99	gold quality
putamen	UBERON:0001874	99.99	gold quality
amygdala	UBERON:0001876	99.99	gold quality
nucleus accumbens	UBERON:0001882	99.99	gold quality
hypothalamus	UBERON:0001898	99.99	gold quality
Ammon’s horn	UBERON:0001954	99.99	gold quality
cerebellum	UBERON:0002037	99.99	gold quality
substantia nigra	UBERON:0002038	99.99	gold quality

Single-cell (SCXA)

Detected in 67 experiment(s), a significant marker in 31.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	39006.60
E-MTAB-10855	yes	34440.71
E-GEOD-111727	yes	32106.91
E-MTAB-7008	yes	26764.72
E-MTAB-6701	yes	26218.93
E-MTAB-8884	yes	25811.39
E-MTAB-7407	yes	24323.73
E-MTAB-8060	yes	23774.59
E-MTAB-6308	yes	23405.54
E-HCAD-6	yes	22833.72
E-HCAD-1	yes	22438.14
E-MTAB-10553	yes	21966.95
E-HCAD-24	yes	21874.38
E-GEOD-180759	yes	20123.01
E-MTAB-8142	yes	19902.94

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• The mutations G3460A and G11778A in the mitochondrial genes MTND1 and MTND4, known to be causative for LHON. (PMID:16137960)
• Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated G11696A mutation in these Chinese pedigrees. (PMID:16364244)
• A novel missense mutation (C11994T) in the ND4 gene, which replaces threonine with isoleucine, was observed in all of the oligoasthenozoospermic men but not in any of the normozoospermic fertile men. (PMID:17069814)
• Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the homoplasmic ND4 G11778A mutation and 33 other variants. (PMID:17300996)
• In situ hybridizations of deparaffinized human lung tissue slices derived from wt-CFTR or cystic fibrosis patients showed downregulation of ND4 in CF. (PMID:17382898)
• result suggests that mtDNA mutation occurs before tumorigenesis and become apparent in cancer cells (PMID:17509949)
• Further analyzed the oligoasthenozoospermic samples from a previous systematic study of infertile Portuguese men and found no instance of C11994T mutation in mitochondrial ND4 gene. (PMID:17517394)
• the G11696A mutation may act in synergy with the primary deafness-associated 12S rRNA A1555G mutation in a Chinese family, thereby increasing the penetrance and expressivity of hearing loss in this Chinese pedigree [case report] (PMID:17723226)
• consisted of forcing mRNAs from nuclearly-encoded ND1 and ND4 genes to localize to the mitochondrial surface (PMID:18513491)
• electroporation with wild-type ND4 prevented both RGC loss and the impairment of visual function. (PMID:18771762)
• The extremely low penetrance of vision loss in these 8 Chinese pedigrees strongly indicates that the G11778A mutation was itself insufficient to produce a clinical phenotype. (PMID:19167085)
• G10680A mutation of ND4 may play a synergistic role with the primary mutation T14484C of ND6, leading to the complete penetrance of Leber’s hereditary optic neuropathy in the presenting family. (PMID:19394449)
• Treatment of acute visual loss due to LHON may be possible with a normal human ND4 subunit gene of complex I, mutated in most cases of LHON, when delivered by an scAAV vector. (PMID:20625049)
• Molecular analysis of mitochondrial genome identified the known ND4 G11778A mutation and 51 variants, belonging to Asian haplogroup C4a1. (PMID:20627642)
• mitochondrial haplogroup M9a specific variant T3394C may modulate the phenotypic manifestation of LHON-associated G11778A mutation in Chinese pedigrees. (PMID:20728388)
• These results suggest that a different set of LHON-causing mutations is present in the South Indian population than in the European population (PMID:20809775)
• Twenty-five subjects with Leber hereditary optic neuropathy (LHON) and 21 carriers positive for the G11778A mitochondrial DNA mutation were recruited. Three additional mutations in the ND4 gene, G11719A, G11947A, or G11914A, were detected. (PMID:20837795)
• The specific mtDNA background B5a1 was significantly associated with Southeast Asian G11778A LHON and appeared to modify the risk of visual loss. (PMID:21398275)
• altered activity of complex III modulates the phenotypic manifestation of Leber’s hereditary optic neuropathy-associated ND4 G11778A mutation (PMID:21742061)
• Patients with somatically acquired ND4 mutations had significantly longer relapse-free survival (P=0.017) and overall survival (OS) (P=0.021) than ND4(wildtype) patients (PMID:21826063)
• Our data emphasize the important role of MTND mutations in the pathogenicity of MELAS, especially MELAS/LS overlap syndrome. (PMID:21850008)
• Expression of WT human ND4 in cells with the G11778A mutation in ND4 led to restoration of defective ATP synthesis. (PMID:22523243)
• Three mutations were significantly related to the presence of epilepsy. These mutations were found at the 8502, 11994, and 13,231 bp of mtDNA, which resulted in amino acid changes at the MT-ATP-8, MT-ND4 and MT-ND5 genes. (PMID:24440288)
• the ND4 gene is the hot spot for mutations associated with Leber’s hereditary optic neuropathy (PMID:26218905)
• The molecular study of a family with one member with Leber hereditary optic neuropathy found the mitochondrial mutation m.11778G>A in MT-ND4. (PMID:26683077)
• The mitochondrial haplogroup D4j specific m.11696G > A mutation may act in synergy with the primary Leber’s hereditary optic neuropathy-associated m.11778G > A mutation, thereby increasing the penetrance and expressivity of visual loss in these Chinese families. (PMID:27159682)
• We identified a genetic association between the MT-ND4 11719 A/G polymorphism and Ulcerative Colitis in the subgroup of males. The male-specific association indicates differences between males and females concerning the impact of mitochondrial gene polymorphisms on the development of Ulcerative Colitis. (PMID:27716073)
• this paper identified m.11240C4T in ND4 as a novel mitochondrial disease-related mtDNA mutation in Leigh syndrome. (PMID:27761019)
• MT-ND4 and MT-TL1 genetic variation might be associated with male infertility in Chinese patients. (PMID:27973917)
• The first detailed study of Indian LHON patients confirm that the m.11778G>A-related LHON in India coexists with multiple different mtDNA haplogroups, unlike the preferential association of west Eurasian haplogroup J and the reported increased clinical penetrance with the J2 subhaplogroup. (PMID:28768321)
• A missense mutation, m.11778G>A (p.R340H), in the ND4 gene was identified in eight patients and three asymptomatic carriers, even though the incidence of this has been considered low in Chinese population. (PMID:29116953)
• This review focuses on the role of mitochondrial genes in causing LHON and therapeutics available for treating the disease. A systematic search has been adopted in various databases using the keywords “LHON,” “mitochondria,” “ND1,” “ND4,” “ND6,” and “therapy” and the following review on mitochondrial genetics. (PMID:29133631)
• In this study, 27.5% mutation was detected in North Indian LHON families. These results suggest that m.G11778A mutation is more frequent in this population. The results of the present study are compatible with studies of an Asian population and Northern European population. (PMID:29133642)
• Our study suggests to include haplogroup T as a possible genetic background influencing LHON penetrance and to consider the increase of mtDNA copy number as a protective factor from vision loss regardless the hetero/homoplasmic status of LHON primary mutations. (PMID:29774306)
• This case series describes three patients with an ND4 m11778G > A mitochondrial DNA mutation who had the concomitant occurrence of Juvemile open-angle glaucoma and Lebers hereditary optic neuropathy. (PMID:30558558)
• Mitochondrial transport mediates survival of retinal ganglion cells in affected LHON patients. (PMID:32277753)
• Complex I mutations synergize to worsen the phenotypic expression of Leber’s hereditary optic neuropathy. (PMID:32723871)
• Long-term screening for primary mitochondrial DNA variants associated with Leber hereditary optic neuropathy: incidence, penetrance and clinical features. (PMID:32861874)
• Visual Outcomes in Leber Hereditary Optic Neuropathy Patients With the m.11778G>A (MTND4) Mitochondrial DNA Mutation. (PMID:32969847)
• Diagnostic value of circulating cell-free mtDNA in patients with suspected thyroid cancer: ND4/ND1 ratio as a new potential plasma marker. (PMID:33035689)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt-nd4	ENSDARG00000063917
mus_musculus	mt-Nd4	ENSMUSG00000064363
rattus_norvegicus	Mt-nd4	ENSRNOG00000029707
drosophila_melanogaster	mt:ND4	FBGN0262952
caenorhabditis_elegans		WBGENE00010963

Paralogs (2): MT-ND2 (ENSG00000198763), MT-ND5 (ENSG00000198786)

Protein

Protein identifiers

Mitochondrial alternative ND4 protein — C0HME5 (reviewed: C0HME5, P03905)

All UniProt accessions (2): P03905, H9EC08

UniProt curated annotations — full annotation on UniProt →

Function. Regulates mitochondrial respiration by decreasing oxygen consumption. Also regulates reactive oxygen species homeostasis.

Subunit / interactions. Self-associates to form homomultimers. Interacts with C1QBP.

Subcellular location. Secreted. Cytoplasm. Mitochondrion.

Miscellaneous. Produced by an alternative reading frame of the MT-ND4 gene which also encodes NADH-ubiquinone oxidoreductase chain 4.

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000260	NADH4_N	Domain
IPR001750	ND/Mrp_TM	Domain
IPR003918	NADH_UbQ_OxRdtase	Family
IPR010227	NADH_Q_OxRdtase_chainM/4	Family

Pfam: PF00361, PF01059

Catalyzed reactions (Rhea), 1 shown:

• a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 H(+)(out) (RHEA:29091)

UniProt features (22 total): transmembrane region 11, sequence variant 8, chain 2, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9I4I	ELECTRON MICROSCOPY	2.63
9TI4	ELECTRON MICROSCOPY	2.66
9CWT	ELECTRON MICROSCOPY	3.44
5XTC	ELECTRON MICROSCOPY	3.7
5XTD	ELECTRON MICROSCOPY	3.7
5XTH	ELECTRON MICROSCOPY	3.9
5XTI	ELECTRON MICROSCOPY	17.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P03905-F1	93.97	0.88

No AlphaFold model available for C0HME5 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5419276	Mitochondrial translation termination
R-HSA-611105	Respiratory electron transport
R-HSA-6799198	Complex I biogenesis

MSigDB gene sets: 411 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_ETHANOL, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ATP_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_OXYGEN_LEVELS

GO Biological Process (12): response to hypoxia (GO:0001666), in utero embryonic development (GO:0001701), mitochondrial electron transport, NADH to ubiquinone (GO:0006120), aerobic respiration (GO:0009060), electron transport coupled proton transport (GO:0015990), cerebellum development (GO:0021549), mitochondrial respiratory chain complex I assembly (GO:0032981), response to nicotine (GO:0035094), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), response to ethanol (GO:0045471), ATP synthesis coupled electron transport (GO:0042773), proton transmembrane transport (GO:1902600)

GO Molecular Function (3): NADH dehydrogenase (ubiquinone) activity (GO:0008137), ubiquinone binding (GO:0048039), NADH dehydrogenase activity (GO:0003954)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), respiratory chain complex I (GO:0045271), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial translation	1
Aerobic respiration and respiratory electron transport	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
oxidative phosphorylation	2
response to stress	1
response to decreased oxygen levels	1
chordate embryonic development	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
energy coupled proton transmembrane transport, against electrochemical gradient	1
metencephalon development	1
anatomical structure development	1
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
response to chemical	1
proton motive force-driven ATP synthesis	1
response to alcohol	1
respiratory electron transport chain	1
monoatomic cation transmembrane transport	1
NADH dehydrogenase activity	1
electron transfer activity	1
proton transmembrane transporter activity	1
oxidoreduction-driven active transmembrane transporter activity	1
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	1
active monoatomic ion transmembrane transporter activity	1
quinone binding	1
oxidoreductase activity, acting on NAD(P)H	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
NADH dehydrogenase complex	1
respiratory chain complex	1
transmembrane transporter complex	1
cellular anatomical structure	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	63
Likely benign	34
Benign	47

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
430685	NC_012920.1(MT-TS2):m.11263_15374del	Pathogenic
9708	NC_012920.1(MT-ND4):m.11778G>A	Pathogenic
9711	NC_012920.1(MT-ND4):m.11777C>A	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
M:10970:T:C	W71R	0.999
M:11402:T:C	W215R	0.999
M:11717:G:T	G320W	0.999
M:10850:A:C	S31R	0.998
M:11165:T:C	W136R	0.998
M:11345:T:C	W196R	0.998
M:11406:T:A	L216H	0.998
M:11406:T:C	L216P	0.998
M:11438:G:T	G227W	0.998
M:11451:T:A	L231H	0.998
M:11457:C:A	A233E	0.998
M:11466:T:C	L236S	0.998
M:11717:G:C	G320R	0.998
M:11718:G:A	G320E	0.998
M:11738:T:C	F327L	0.998
M:11740:C:A	F327L	0.998
M:11740:C:G	F327L	0.998
M:10980:C:G	P74R	0.997
M:11438:G:C	G227R	0.997
M:11454:C:A	A232D	0.997
M:11466:T:G	L236W	0.997
M:11484:G:A	G242D	0.997
M:11493:G:C	R245P	0.997
M:11561:G:C	G268R	0.997
M:11628:C:G	S290W	0.997
M:11633:A:C	S292R	0.997
M:11714:C:G	H319D	0.997
M:11716:C:A	H319Q	0.997
M:11716:C:G	H319Q	0.997
M:11730:C:G	S324W	0.997

dbSNP variants (sampled 300 via entrez): RS1057516063 (MT:9166 T>C), RS1057516064 (MT:9237 G>A), RS1057516065 (MT:11896 C>G), RS1057516066 (MT:12010 C>A,T), RS1057516067 (MT:12013 A>G), RS1057516068 (MT:12018 C>G,T), RS1057520074 (MT:10499 A>G), RS1057520079 (MT:9091 A>G), RS1057520099 (MT:12175 T>C), RS1057520102 (MT:8816 A>G), RS1057520176 (MT:11428 C>A,T), RS1057520204 (MT:8943 C>T), RS112133961 (MT:10127 A>G), RS1131692061 (MT:12271 T>C), RS1131692062 (MT:12283 G>A)

Disease associations

OMIM: gene MIM:516003 | disease phenotypes: MIM:256000, MIM:535000, MIM:308905, MIM:540000, MIM:500001

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber hereditary optic neuropathy	Definitive	Mitochondrial
maternally-inherited Leigh syndrome	Supportive	Mitochondrial
MELAS syndrome	Supportive	Mitochondrial
Leber plus disease	Supportive	Mitochondrial

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	MT
Leigh syndrome	Definitive	MT

Mondo (23): Leigh syndrome (MONDO:0009723), venous thromboembolism (MONDO:0005399), dementia (MONDO:0001627), epilepsy (MONDO:0005027), peripheral neuropathy (MONDO:0005244), hearing loss disorder (MONDO:0005365), dystonic disorder (MONDO:0003441), microcephaly (MONDO:0001149), mitochondrial disease (MONDO:0044970), ependymoma (MONDO:0016698), Leber hereditary optic neuropathy (MONDO:0010788), optic nerve disorder (MONDO:0002135), optic atrophy (MONDO:0003608), optic neuritis (MONDO:0005885), mitochondrial complex I deficiency (MONDO:0100133)

Orphanet (9): Leigh syndrome (Orphanet:506), Mitochondrial disease (Orphanet:68380), Ependymoma (Orphanet:251636), Leber hereditary optic neuropathy (Orphanet:104), Isolated complex I deficiency (Orphanet:2609), OBSOLETE: Inherited retinal disorder (Orphanet:71862), MELAS (Orphanet:550), Leber plus disease (Orphanet:99718), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

146 total (30 of 146 shown, HPO-id order):

HPO	Term
HP:0000044	Hypogonadotropic hypogonadism
HP:0000091	Abnormal renal tubule morphology
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000112	Nephropathy
HP:0000114	Proximal tubulopathy
HP:0000407	Sensorineural hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000529	Progressive visual loss
HP:0000551	Color vision defect
HP:0000572	Visual loss
HP:0000576	Centrocecal scotoma
HP:0000580	Pigmentary retinopathy
HP:0000590	Progressive external ophthalmoplegia
HP:0000597	Ophthalmoparesis
HP:0000603	Central scotoma
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000726	Dementia
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000751	Personality changes
HP:0000816	Abnormality of Krebs cycle metabolism
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism

GWAS associations

0 associations (top):

MeSH disease descriptors (19)

Descriptor	Name	Tree numbers
D003704	Dementia	C10.228.140.380; F03.615.400
D020821	Dystonic Disorders	C10.228.662.300
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290
D004827	Epilepsy	C10.228.140.490
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520
D017241	MELAS Syndrome	C05.651.460.620.520; C10.228.140.163.100.535; C10.228.140.300.275.500; C10.668.491.500.500.500; C14.907.253.329.500; C16.320.565.189.535; C18.452.132.100.535; C18.452.648.189.535; C18.452.660.560.620.520
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D029242	Optic Atrophy, Hereditary, Leber	C10.292.700.225.500.400; C10.574.500.662.400; C11.270.564.400; C11.640.451.451.400; C16.320.290.564.400; C16.320.400.630.400; C18.452.660.670
D009901	Optic Nerve Diseases	C10.292.700; C11.640
D009902	Optic Neuritis	C10.292.700.550; C11.640.576
D058499	Retinal Dystrophies	C11.768.585.658
D020521	Stroke	C10.228.140.300.775; C14.907.253.855
D054556	Venous Thromboembolism	C14.907.355.590.700
C536024	Marsden syndrome (supp.)
C536035	Maternally Inherited Leigh Syndrome (supp.)
C537475	Mitochondrial complex I deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2853826	MT-CO3, MT-ND3, MT-ND4, MT-ND4L, MT-ND5	3	2.00	1	efavirenz;lopinavir;Nucleoside and nucleotide reverse transcriptase inhibitors;ritonavir

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
enniatins	affects cotreatment, decreases expression, increases expression	5
Air Pollutants	decreases expression, increases abundance	4
beauvericin	affects cotreatment, decreases expression, increases expression	3
Atrazine	decreases expression	2
Lipopolysaccharides	affects response to substance, affects cotreatment, decreases expression, affects expression	2
Plant Extracts	increases expression, decreases expression, affects cotreatment	2
Valproic Acid	decreases expression, decreases methylation, increases expression	2
Zidovudine	affects expression, increases expression	2
1-Methyl-4-phenylpyridinium	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol A	decreases expression	1
ochratoxin A	affects cotreatment, decreases expression, increases expression	1
aflatoxin G1	affects cotreatment, increases expression	1
aflatoxin B2	affects cotreatment, increases expression	1
aflatoxin G2	affects cotreatment, increases expression	1
tris(chloroethyl)phosphate	increases abundance, increases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
licochalcone B	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Arsenic	increases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases expression, increases abundance	1
Cholecalciferol	decreases expression	1
Doxorubicin	increases expression	1
Dust	decreases expression, increases abundance	1
Ethidium	decreases expression	1
Etoposide	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 transformed cell line, 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4N43	GM04368	Transformed cell line	Male
CVCL_RP84	TVGH-iPSC-010-09	Induced pluripotent stem cell	Female
CVCL_UN90	HPS1776	Induced pluripotent stem cell	Male
CVCL_Y652	GM10742	Transformed cell line	Male
CVCL_Y653	GM10744	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01831934	PHASE4	COMPLETED	Responses to Influenza Vaccine in Patients With Mitochondrial Disorders (MELAS)
NCT00077753	PHASE4	COMPLETED	EXCLAIM:Extended Prophylaxis for Venous ThromboEmbolism (VTE) in Acutely Ill Medical Patients With Prolonged Immobilization
NCT00196118	PHASE4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00437697	PHASE4	TERMINATED	Thromboprophylaxis in Critically Ill Patients
NCT00445328	PHASE4	TERMINATED	Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients
NCT00689520	PHASE4	COMPLETED	Long-Term Low-Molecular-Weight Heparin Versus Oral Anticoagulants in Deep Venous Thrombosis
NCT00851864	PHASE4	COMPLETED	Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT00967304	PHASE4	COMPLETED	Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
NCT01119261	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol
NCT01119274	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon
NCT01119300	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin
NCT01210755	PHASE4	COMPLETED	Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
NCT01304108	PHASE4	COMPLETED	Improving Venous Thromboembolism Prophylaxis
NCT01467583	PHASE4	COMPLETED	Fondaparinux in Critically Ill Patients With Renal Failure
NCT01916707	PHASE4	UNKNOWN	Weight Based Enoxaparin in Trauma Patients
NCT02095509	PHASE4	COMPLETED	Pharmacokinetics of Enoxaparin in Intensive Care Patients
NCT02396732	PHASE4	TERMINATED	Aspirin and Enoxaparin for VTE in Trauma
NCT02412982	PHASE4	COMPLETED	Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients
NCT02464969	PHASE4	COMPLETED	Apixaban for the Acute Treatment of Venous Thromboembolism in Children
NCT02474212	PHASE4	COMPLETED	: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery
NCT02559856	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study
NCT02856295	PHASE4	COMPLETED	anti10a Levels in Women Treated With LMWH in the Postpartum Period
NCT02945280	PHASE4	TERMINATED	Apixaban for Routine Management of Upper Extremity Deep Venous Thrombosis
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03006562	PHASE4	TERMINATED	PREvention of VENous ThromboEmbolism Following Radical Prostatectomy
NCT03158792	PHASE4	COMPLETED	Enoxaparin 20mg Versus 30mg Subcutaneously Once Daily in Elderly Patients With Impaired Renal Function
NCT03196349	PHASE4	TERMINATED	Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT03266783	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism
NCT03426982	PHASE4	UNKNOWN	Comparision Between Activated Partial Thromboplastin Time Versus Anti-Xa Activity in Heparin Monitoring
NCT03678506	PHASE4	TERMINATED	Apixaban for Extended Anticoagulation (APIDULCIS)
NCT03988101	PHASE4	COMPLETED	Role of Statin in Venous Dysfunction in Patients With Venous Thromboembolism Event
NCT03988231	PHASE4	WITHDRAWN	Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study
NCT04128254	PHASE4	UNKNOWN	A Prospective Study in Chinese Patients With Lower Extremity Ankle Fracture of Oral Anticoagulants to Prevent Venous Thromboembolism (VTE)
NCT04157881	PHASE4	COMPLETED	A Study on the Impact of Rabeprazole-induced Elevated Stomach pH on APO-Dabigatran Exposure in Healthy Volunteers
NCT04168203	PHASE4	COMPLETED	Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism
NCT04169269	PHASE4	UNKNOWN	Deep Vein Thrombosis Prophylaxis Adherence: Enoxaparin vs Rivaroxaban
NCT04263038	PHASE4	RECRUITING	Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy