MC1DN1
MCID: MTC146
MIFTS: 59

Mitochondrial Complex I Deficiency, Nuclear Type 1 (MC1DN1)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mitochondrial Complex I Deficiency, Nuclear Type 1

MalaCards integrated aliases for Mitochondrial Complex I Deficiency, Nuclear Type 1:

Name: Mitochondrial Complex I Deficiency, Nuclear Type 1 57 72 29 6
Mitochondrial Complex I Deficiency 57 12 20 43 72 36 29 54 6 44 15 39 70
Nadh:q(1) Oxidoreductase Deficiency 57 20 43 72 70
Isolated Mitochondrial Respiratory Chain Complex I Deficiency 12 20 58
Isolated Nadh-Coenzyme Q Reductase Deficiency 12 20 58
Isolated Nadh-Ubiquinone Reductase Deficiency 12 20 58
Isolated Nadh-Coq Reductase Deficiency 12 20 58
Nadh-Coenzyme Q Reductase Deficiency 57 43 72
Mc1dn1 57 12 72
Mitochondrial Nadh Dehydrogenase Component of Complex I, Deficiency of 57 20
Isolated Complex I Deficiency 20 58
Deficiency of Mitochondrial Nadh Dehydrogenase Component of Complex I 72
Complex I, Mitochondrial Respiratory Chain, Deficiency of 13
Complex 1 Mitochondrial Respiratory Chain Deficiency 20
Complex I Mitochondrial Respiratory Chain Deficiency 72
Nuclear Type Mitochondrial Complex I Deficiency 1 12
Nadh:ubiquinone Oxidoreductase Deficiency 72
Nadh Coenzyme Q Reductase Deficiency 20

Characteristics:

Orphanet epidemiological data:

58
isolated complex i deficiency
Inheritance: Autosomal recessive,Mitochondrial inheritance,X-linked dominant; Age of onset: All ages; Age of death: any age;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
onset in infancy
early death may occur


HPO:

31
mitochondrial complex i deficiency, nuclear type 1:
Inheritance autosomal recessive inheritance x-linked dominant inheritance mitochondrial inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Mitochondrial Complex I Deficiency, Nuclear Type 1

MedlinePlus Genetics : 43 Mitochondrial complex I deficiency is a shortage (deficiency) of a protein complex called complex I or a loss of its function. Complex I is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex I is the first of five mitochondrial complexes that carry out a multi-step process called oxidative phosphorylation, through which cells derive much of their energy.Mitochondrial complex I deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system, the heart, and the muscles used for movement (skeletal muscles). These signs and symptoms can appear at any time from birth to adulthood.People with mitochondrial complex I deficiency typically have neurological problems, such as abnormal brain function (encephalopathy), recurrent seizures (epilepsy), intellectual disability, difficulty coordinating movements (ataxia), or involuntary movements (dystonia). Affected individuals may have low muscle tone (hypotonia), muscle pain (myalgia), and extreme fatigue in response to physical activity (exercise intolerance). They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. In severe cases, lactic acidosis can be life-threatening.People with mitochondrial complex I deficiency sometimes have heart, liver, or kidney problems. Vision problems due to abnormal eye movement or breakdown (degeneration) of the nerves that carry signals from the eyes to the brain (optic nerves) can also occur.Some people with mitochondrial complex I deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, a condition called Leigh syndrome is most commonly caused by mitochondrial complex I deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years from the onset of symptoms. Another condition that can be caused by mitochondrial complex I deficiency, Leber hereditary optic neuropathy, is associated mainly with vision problems due to optic nerve degeneration. These syndromes can also have other causes.

MalaCards based summary : Mitochondrial Complex I Deficiency, Nuclear Type 1, also known as mitochondrial complex i deficiency, is related to mitochondrial complex i deficiency, nuclear type 10 and mitochondrial complex i deficiency, nuclear type 7, and has symptoms including seizures, ataxia and muscle weakness. An important gene associated with Mitochondrial Complex I Deficiency, Nuclear Type 1 is NDUFS4 (NADH:Ubiquinone Oxidoreductase Subunit S4), and among its related pathways/superpathways are Oxidative phosphorylation and Metabolism. Affiliated tissues include eye, heart and brain, and related phenotypes are decreased activity of mitochondrial complex i and failure to thrive

Disease Ontology : 12 A mitochondrial metabolism disease characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome. It can have material basis in mutations in multiple different genes, both nuclear-encoded and mitochondrial-encoded.

GARD : 20 Mitochondrial complex I deficiency is a type of mitochondrial disease. Mitochondria are specialized compartments in cells that create more than 90% of the energy needed by the body. In mitochondrial diseases, the mitochondria don't work correctly resulting in less energy in the cell, cell injury and cell death. Complex I is the first step in a chain reaction in mitochondria leading to energy production. Signs and symptoms of complex I deficiency vary widely in nature and severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Features may include macrocephaly (large head) with progressive leukodystrophy, encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. The disease is caused by mutations in any of many genes and the inheritance pattern depends on the responsible gene. Treatment is only helpful in some case but may include metabolic therapies such as riboflavin, thiamine, biotin, co-enzyme Q10, carnitine, and a ketogenic diet (a special high-fat, low-carbohydrate diet).

OMIM® : 57 Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (see 256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). (252010) (Updated 20-May-2021)

KEGG : 36 Mitochondrial complex I deficiency, the most common mitochondrial disorders, is a group of highly heterogeneous conditions characterised by faulty oxidative phosphorylation (OXPHOS). Human complex I is a giant multiheteromeric structure. Complex I deficiency is known to be associated with a broad spectrum of clinical presentations, that include encephalopathy, cardiomyopathy, myopathy, and liver disease.

UniProtKB/Swiss-Prot : 72 Mitochondrial complex I deficiency, nuclear type 1: A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non- specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.

Related Diseases for Mitochondrial Complex I Deficiency, Nuclear Type 1

Diseases related to Mitochondrial Complex I Deficiency, Nuclear Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 135)
# Related Disease Score Top Affiliating Genes
1 mitochondrial complex i deficiency, nuclear type 10 33.4 NDUFAF2 ERCC8
2 mitochondrial complex i deficiency, nuclear type 7 33.4 NDUFV2-AS1 NDUFV2
3 leigh syndrome 33.3 TMEM126B TIMMDC1 NUBPL NDUFV2-AS1 NDUFV2 NDUFV1
4 mitochondrial disorders 31.6 TMEM126B NDUFV1 NDUFS4 NDUFS2 NDUFS1 MT-ND4
5 mitochondrial metabolism disease 31.6 NDUFV1 NDUFS4 NDUFS2 NDUFAF2 MT-ND4 FOXRED1
6 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 31.5 TMEM126B NDUFV2 NDUFS2 NDUFS1 NDUFB3 NDUFAF2
7 mitochondrial encephalomyopathy 31.0 NDUFS4 MT-ND4 MT-ND2
8 hereditary optic neuropathy 31.0 MT-ND4 MT-ND2
9 leukodystrophy 30.9 TMEM126B NUBPL NDUFV2 NDUFV1 NDUFS6 NDUFS4
10 optic nerve disease 30.8 NDUFS4 MT-ND4 MT-ND2
11 neuropathy 30.8 NDUFS4 NDUFS2 NDUFS1 NDUFB11 MT-ND4 MT-ND2
12 mitochondrial dna-associated leigh syndrome and narp 30.6 MT-ND4 MT-ND2
13 mitochondrial complex i deficiency, nuclear type 20 11.9
14 mitochondrial complex i deficiency, mitochondrial type 1 11.8
15 mitochondrial complex i deficiency, nuclear type 6 11.8
16 mitochondrial complex i deficiency, nuclear type 8 11.8
17 mitochondrial complex i deficiency, nuclear type 9 11.8
18 mitochondrial complex i deficiency, nuclear type 14 11.8
19 mitochondrial complex i deficiency, nuclear type 25 11.8
20 mitochondrial complex i deficiency, nuclear type 27 11.8
21 mitochondrial complex i deficiency, nuclear type 32 11.8
22 mitochondrial complex i deficiency, nuclear type 33 11.8
23 mitochondrial complex iii deficiency, nuclear type 1 11.8
24 mitochondrial complex i deficiency, nuclear type 12 11.8
25 mitochondrial complex i deficiency, nuclear type 30 11.8
26 mitochondrial complex i deficiency, nuclear type 11 11.8
27 mitochondrial complex i deficiency, nuclear type 13 11.8
28 mitochondrial complex i deficiency, nuclear type 15 11.8
29 mitochondrial complex i deficiency, nuclear type 16 11.8
30 mitochondrial complex i deficiency, nuclear type 17 11.8
31 mitochondrial complex i deficiency, nuclear type 18 11.8
32 mitochondrial complex i deficiency, nuclear type 19 11.8
33 mitochondrial complex i deficiency, nuclear type 21 11.8
34 mitochondrial complex i deficiency, nuclear type 22 11.8
35 mitochondrial complex i deficiency, nuclear type 23 11.8
36 mitochondrial complex i deficiency, nuclear type 24 11.8
37 mitochondrial complex i deficiency, nuclear type 26 11.8
38 mitochondrial complex i deficiency, nuclear type 28 11.8
39 mitochondrial complex i deficiency, nuclear type 29 11.8
40 mitochondrial complex i deficiency, nuclear type 31 11.8
41 mitochondrial complex i deficiency, nuclear type 34 11.8
42 mitochondrial complex i deficiency, nuclear type 35 11.8
43 mitochondrial complex v deficiency, nuclear type 1 11.7
44 mitochondrial complex iv deficiency, nuclear type 1 11.7
45 mitochondrial complex ii deficiency, nuclear type 1 11.7
46 mitochondrial complex i deficiency, nuclear type 36 11.7
47 nuclear type mitochondrial complex i deficiency 11.6
48 mitochondrial type mitochondrial complex i deficiency 11.5
49 mitochondrial complex i deficiency, nuclear type 37 11.4
50 nephronophthisis-like nephropathy 1 11.2

Graphical network of the top 20 diseases related to Mitochondrial Complex I Deficiency, Nuclear Type 1:



Diseases related to Mitochondrial Complex I Deficiency, Nuclear Type 1

Symptoms & Phenotypes for Mitochondrial Complex I Deficiency, Nuclear Type 1

Human phenotypes related to Mitochondrial Complex I Deficiency, Nuclear Type 1:

58 31 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 decreased activity of mitochondrial complex i 58 31 obligate (100%) Obligate (100%) HP:0011923
2 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
3 ptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000508
4 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
5 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
6 respiratory insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002093
7 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
8 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
9 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
10 vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002013
11 hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001943
12 strabismus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000486
13 intrauterine growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001511
14 hypertrophic cardiomyopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001639
15 lethargy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001254
16 proximal tubulopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000114
17 optic disc pallor 58 31 hallmark (90%) Very frequent (99-80%) HP:0000543
18 poor eye contact 58 31 hallmark (90%) Very frequent (99-80%) HP:0000817
19 optic neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001138
20 encephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001298
21 leukoencephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002352
22 leukodystrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002415
23 poor head control 58 31 hallmark (90%) Very frequent (99-80%) HP:0002421
24 increased csf lactate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002490
25 lactic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0003128
26 increased serum pyruvate 58 31 hallmark (90%) Very frequent (99-80%) HP:0003542
27 mitochondrial myopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003737
28 paroxysmal involuntary eye movements 58 31 hallmark (90%) Very frequent (99-80%) HP:0007704
29 abnormal mitochondria in muscle tissue 58 31 hallmark (90%) Very frequent (99-80%) HP:0008316
30 focal t2 hyperintense brainstem lesion 58 31 hallmark (90%) Very frequent (99-80%) HP:0012748
31 hypotonia 31 hallmark (90%) HP:0001252
32 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
33 microcephaly 58 31 very rare (1%) Occasional (29-5%) HP:0000252
34 blindness 58 31 occasional (7.5%) Occasional (29-5%) HP:0000618
35 feeding difficulties 58 31 occasional (7.5%) Occasional (29-5%) HP:0011968
36 fetal distress 58 31 occasional (7.5%) Occasional (29-5%) HP:0025116
37 spasticity 31 HP:0001257
38 hyperreflexia 31 HP:0001347
39 muscular hypotonia 58 Very frequent (99-80%)
40 muscle weakness 58 Very frequent (99-80%)
41 developmental regression 31 HP:0002376
42 dyskinesia 31 HP:0100660
43 feeding difficulties in infancy 31 HP:0008872
44 skeletal muscle atrophy 31 HP:0003202
45 growth delay 31 HP:0001510
46 hepatic failure 31 HP:0001399
47 hyporeflexia 31 HP:0001265
48 babinski sign 31 HP:0003487
49 respiratory failure 31 HP:0002878
50 cerebellar atrophy 31 HP:0001272

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
ataxia
hyporeflexia
lethargy
encephalopathy
more
Head And Neck Eyes:
ptosis
nystagmus
blindness
strabismus
poor eye contact
more
Respiratory:
respiratory insufficiency
respiratory failure

Abdomen Gastrointestinal:
vomiting
poor feeding

Cardiovascular Heart:
hypertrophic cardiomyopathy

Head And Neck Ears:
sensorineural deafness
auditory neuropathy

Growth Other:
failure to thrive
growth retardation

Muscle Soft Tissue:
muscle weakness
hypotonia

Abdomen Liver:
hepatomegaly

Metabolic Features:
hypoglycemia
lactic acidosis

Laboratory Abnormalities:
increased csf lactate
lactic acidemia
decreased activity of mitochondrial respiratory chain complex i in various tissues

Head And Neck Head:
microcephaly (in some patients)

Clinical features from OMIM®:

252010 (Updated 20-May-2021)

UMLS symptoms related to Mitochondrial Complex I Deficiency, Nuclear Type 1:


seizures; ataxia; muscle weakness; vomiting; lethargy; muscle spasticity

GenomeRNAi Phenotypes related to Mitochondrial Complex I Deficiency, Nuclear Type 1 according to GeneCards Suite gene sharing:

26 (show all 20)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.64 NDUFV2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-119 9.64 NDUFB9
3 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.64 NDUFB9 NDUFS1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-124 9.64 NDUFB9
5 Increased shRNA abundance (Z-score > 2) GR00366-A-133 9.64 NDUFS1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-145 9.64 NDUFS1 NDUFV2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-148 9.64 NDUFB9
8 Increased shRNA abundance (Z-score > 2) GR00366-A-160 9.64 NDUFV2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.64 NDUFS1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-18 9.64 NDUFB9
11 Increased shRNA abundance (Z-score > 2) GR00366-A-195 9.64 NDUFV1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.64 NDUFV2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-27 9.64 NDUFV2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-35 9.64 NDUFB9
15 Increased shRNA abundance (Z-score > 2) GR00366-A-4 9.64 NDUFS1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-40 9.64 NDUFV2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.64 NDUFB9
18 Increased shRNA abundance (Z-score > 2) GR00366-A-77 9.64 NDUFB9
19 Increased shRNA abundance (Z-score > 2) GR00366-A-78 9.64 NDUFV1
20 Decreased shRNA abundance GR00297-A 9.35 NDUFB9 NDUFS1 NDUFS2 NDUFV1 NDUFV2

Drugs & Therapeutics for Mitochondrial Complex I Deficiency, Nuclear Type 1

Search Clinical Trials , NIH Clinical Center for Mitochondrial Complex I Deficiency, Nuclear Type 1

Cochrane evidence based reviews: mitochondrial complex i deficiency

Genetic Tests for Mitochondrial Complex I Deficiency, Nuclear Type 1

Genetic tests related to Mitochondrial Complex I Deficiency, Nuclear Type 1:

# Genetic test Affiliating Genes
1 Mitochondrial Complex I Deficiency 29
2 Mitochondrial Complex I Deficiency, Nuclear Type 1 29 NDUFS4

Anatomical Context for Mitochondrial Complex I Deficiency, Nuclear Type 1

MalaCards organs/tissues related to Mitochondrial Complex I Deficiency, Nuclear Type 1:

40
Eye, Heart, Brain, Skeletal Muscle, Colon, Temporal Lobe, Kidney

Publications for Mitochondrial Complex I Deficiency, Nuclear Type 1

Articles related to Mitochondrial Complex I Deficiency, Nuclear Type 1:

(show top 50) (show all 170)
# Title Authors PMID Year
1
Uniparental isodisomy as a cause of mitochondrial complex I respiratory chain disorder due to a novel splicing NDUFS4 mutation. 57 6
33093004 2020
2
Functional characterization of the c.462delA mutation in the NDUFS4 subunit gene of mitochondrial complex I. 6 57
24020637 2014
3
A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family. 6 57
19107570 2008
4
A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome. 6 57
11181577 2001
5
Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene. 6 57
10944442 2000
6
Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit. 57 6
9463323 1998
7
Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I deficiency. 6 61 54
19384974 2009
8
Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts. 61 54 57
10393702 1999
9
Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing. 57 61
22499348 2012
10
Next-generation sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation. 6 61
22072591 2012
11
Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9. 61 6
22200994 2012
12
NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency. 57 61
15372108 2004
13
Familial mitochondrial complex I deficiency with an abnormal mitochondrial encoded protein. 57 61
2512443 1989
14
SLC25A10 biallelic mutations in intractable epileptic encephalopathy with complex I deficiency. 6
29211846 2018
15
Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. 6
26795593 2016
16
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
17
Characterization of clinically identified mutations in NDUFV1, the flavin-binding subunit of respiratory complex I, using a yeast model system. 6
26345448 2015
18
Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and sensorial deficiencies, and mitochondrial complex I instability. 6
25901006 2015
19
Targeted exome sequencing for mitochondrial disorders reveals high genetic heterogeneity. 6
24215330 2013
20
A novel familial case of diffuse leukodystrophy related to NDUFV1 compound heterozygous mutations. 6
23562761 2013
21
Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7. 6
21607760 2012
22
Respiratory chain complex I deficiency caused by mitochondrial DNA mutations. 57
21364701 2011
23
A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency. 57
20972245 2011
24
High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. 6
20818383 2010
25
The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families. 6
20819849 2010
26
Siblings with leukoencephalopathy. 6
19073330 2008
27
C6ORF66 is an assembly factor of mitochondrial complex I. 6
18179882 2008
28
A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. 6
16200211 2005
29
Nonsense mutations in mitochondrial DNA associated with myalgia and exercise intolerance. 6
15781840 2005
30
De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency. 57
14705112 2004
31
Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome. 57
14729820 2004
32
Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome. 57
12616398 2003
33
Paternal inheritance of mitochondrial DNA. 6
12192017 2002
34
Respiratory chain complex I deficiency. 57
11579423 2001
35
Isolated complex I deficiency in children: clinical, biochemical and genetic aspects. 57
10649489 2000
36
Human mitochondrial complex I in health and disease. 57
10330338 1999
37
Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. 6
10080174 1999
38
A high rate (20%-30%) of parental consanguinity in cytochrome-oxidase deficiency. 57
9683589 1998
39
Fate of microinjected spermatid mitochondria in the mouse oocyte and embryo. 6
9854792 1998
40
Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect. 57
9593934 1998
41
New familial mitochondrial encephalopathy with macrocephaly, cardiomyopathy, and complex I deficiency. 57
9382480 1997
42
Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. 6
8644732 1996
43
NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings. 57
8892026 1996
44
Human diseases with defects in oxidative phosphorylation. 1. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies. 57
7867654 1995
45
Paternal inheritance of mitochondrial DNA in mice. 6
1857422 1991
46
Congenital deficiency of a 20-kDa subunit of mitochondrial complex I in fibroblasts. 57
1903590 1991
47
Familial NADH: Q1 oxidoreductase (complex I) deficiency: variable expression and possible treatment. 57
2512441 1989
48
Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy. 57
3110216 1987
49
Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I. 57
3100577 1987
50
Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis. 57
6432847 1984

Variations for Mitochondrial Complex I Deficiency, Nuclear Type 1

ClinVar genetic disease variations for Mitochondrial Complex I Deficiency, Nuclear Type 1:

6 (show top 50) (show all 930)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NUBPL NM_025152.3(NUBPL):c.166G>A (p.Gly56Arg) SNV Pathogenic 7 rs200401432 GRCh37: 14:32031331-32031331
GRCh38: 14:31562125-31562125
2 NDUFAF4 NM_014165.4(NDUFAF4):c.194T>C (p.Leu65Pro) SNV Pathogenic 790 rs63751061 GRCh37: 6:97344666-97344666
GRCh38: 6:96896790-96896790
3 NDUFS4 NM_002495.4(NDUFS4):c.466_470dup (p.Lys158fs) Duplication Pathogenic 6887 rs1445075330 GRCh37: 5:52978987-52978988
GRCh38: 5:53683157-53683158
4 NDUFS4 NM_002495.4(NDUFS4):c.291del (p.Lys96_Trp97insTer) Deletion Pathogenic 6888 rs121908985 GRCh37: 5:52942175-52942175
GRCh38: 5:53646345-53646345
5 NDUFS4 NM_002495.4(NDUFS4):c.44G>A (p.Trp15Ter) SNV Pathogenic 6890 rs104893899 GRCh37: 5:52856536-52856536
GRCh38: 5:53560706-53560706
6 NDUFS4 NM_002495.4(NDUFS4):c.99-1G>A SNV Pathogenic 496165 rs376281345 GRCh37: 5:52899281-52899281
GRCh38: 5:53603451-53603451
7 MT-ND2 m.5132_5133delAA Deletion Pathogenic 9719 rs199476116 GRCh37: MT:5132-5133
GRCh38: MT:5132-5133
8 MT-ND2 m.4810G>A SNV Pathogenic 9720 rs267606888 GRCh37: MT:4810-4810
GRCh38: MT:4810-4810
9 NDUFA13 NM_015965.7(NDUFA13):c.170G>A (p.Arg57His) SNV Pathogenic 132643 rs752513525 GRCh37: 19:19637066-19637066
GRCh38: 19:19526257-19526257
10 NDUFS4 NM_002495.4(NDUFS4):c.462del (p.Lys154fs) Deletion Pathogenic 40257 rs587776949 GRCh37: 5:52978982-52978982
GRCh38: 5:53683152-53683152
11 NDUFS4 NM_002495.4(NDUFS4):c.316C>T (p.Arg106Ter) SNV Pathogenic 6889 rs104893898 GRCh37: 5:52942201-52942201
GRCh38: 5:53646371-53646371
12 FOXRED1 NM_017547.4(FOXRED1):c.406C>T (p.Arg136Trp) SNV Pathogenic 372745 rs373075574 GRCh37: 11:126142963-126142963
GRCh38: 11:126273068-126273068
13 NDUFV1 NM_007103.4(NDUFV1):c.1118T>C (p.Phe373Ser) SNV Pathogenic 431452 rs1135402749 GRCh37: 11:67379405-67379405
GRCh38: 11:67611934-67611934
14 NDUFS4 NM_002495.4(NDUFS4):c.316C>T (p.Arg106Ter) SNV Pathogenic 6889 rs104893898 GRCh37: 5:52942201-52942201
GRCh38: 5:53646371-53646371
15 NDUFB11 NM_019056.6(NDUFB11):c.262C>T (p.Arg88Ter) SNV Pathogenic 190302 rs786205225 GRCh37: X:47002089-47002089
GRCh38: X:47142690-47142690
16 NDUFS1 NM_005006.7(NDUFS1):c.64C>T (p.Arg22Ter) SNV Pathogenic 626277 rs750971390 GRCh37: 2:207017232-207017232
GRCh38: 2:206152508-206152508
17 NDUFV1 NM_007103.4(NDUFV1):c.1162+4A>C SNV Pathogenic 372716 rs199683937 GRCh37: 11:67379453-67379453
GRCh38: 11:67611982-67611982
18 NDUFS4 NM_002495.4(NDUFS4):c.350+5G>A SNV Pathogenic 930177 GRCh37: 5:52942240-52942240
GRCh38: 5:53646410-53646410
19 TIMMDC1 NM_016589.4(TIMMDC1):c.385C>T (p.Arg129Ter) SNV Pathogenic 983214 rs970547270 GRCh37: 3:119222403-119222403
GRCh38: 3:119503556-119503556
20 TMEM126B NM_018480.7(TMEM126B):c.137del (p.Ala46fs) Deletion Pathogenic 997635 GRCh37: 11:85342786-85342786
GRCh38: 11:85631742-85631742
21 NDUFS1 NM_005006.7(NDUFS1):c.683T>C (p.Val228Ala) SNV Pathogenic 429933 rs370411488 GRCh37: 2:207011681-207011681
GRCh38: 2:206146957-206146957
22 NDUFS6 NM_004553.6(NDUFS6):c.32_33dup (p.Asn12Ter) Duplication Pathogenic 1030816 GRCh37: 5:1801562-1801563
GRCh38: 5:1801448-1801449
23 NDUFS2 NM_001377299.1(NDUFS2):c.1354+18T>C SNV Pathogenic 1032229 GRCh37: 1:161183729-161183729
GRCh38: 1:161213939-161213939
24 TMEM126B NM_018480.7(TMEM126B):c.320_321del (p.Tyr107fs) Microsatellite Pathogenic 1032805 GRCh37: 11:85345244-85345245
GRCh38: 11:85634200-85634201
25 ERCC8 , NDUFAF2 NM_174889.5(NDUFAF2):c.114C>G (p.Tyr38Ter) SNV Pathogenic 419231 rs199754807 GRCh37: 5:60241196-60241196
GRCh38: 5:60945369-60945369
26 NDUFB9 NM_005005.3(NDUFB9):c.148G>T (p.Glu50Ter) SNV Pathogenic 1032961 GRCh37: 8:125555374-125555374
GRCh38: 8:124543133-124543133
27 TIMMDC1 NM_016589.4(TIMMDC1):c.814del (p.Leu272fs) Deletion Pathogenic 1033832 GRCh37: 3:119242558-119242558
GRCh38: 3:119523711-119523711
28 MT-ND4 m.11777C>A SNV Pathogenic 9711 rs28384199 GRCh37: MT:11777-11777
GRCh38: MT:11777-11777
29 NDUFB3 NM_002491.3(NDUFB3):c.208G>T (p.Gly70Ter) SNV Pathogenic 39836 rs200800978 GRCh37: 2:201950249-201950249
GRCh38: 2:201085526-201085526
30 NDUFS4 NM_002495.4(NDUFS4):c.350+5G>A SNV Pathogenic 930177 GRCh37: 5:52942240-52942240
GRCh38: 5:53646410-53646410
31 NDUFV2 , NDUFV2-AS1 NM_021074.5(NDUFV2):c.427C>T (p.Arg143Ter) SNV Pathogenic 1033973 GRCh37: 18:9122637-9122637
GRCh38: 18:9122639-9122639
32 NDUFAF3 NM_199069.2(NDUFAF3):c.188dup (p.Tyr63Ter) Duplication Pathogenic 377248 rs756339822 GRCh37: 3:49059888-49059889
GRCh38: 3:49022455-49022456
33 NDUFAF3 NM_199069.2(NDUFAF3):c.489_490del (p.Gly164fs) Deletion Pathogenic 372432 rs746835381 GRCh37: 3:49060539-49060540
GRCh38: 3:49023106-49023107
34 NDUFV1 NM_007103.4(NDUFV1):c.1268C>T (p.Thr423Met) SNV Pathogenic/Likely pathogenic 14056 rs121913659 GRCh37: 11:67379696-67379696
GRCh38: 11:67612225-67612225
35 NDUFV1 NM_007103.4(NDUFV1):c.1268C>T (p.Thr423Met) SNV Pathogenic/Likely pathogenic 14056 rs121913659 GRCh37: 11:67379696-67379696
GRCh38: 11:67612225-67612225
36 FOXRED1 NM_017547.4(FOXRED1):c.612_615dup (p.Ala206fs) Duplication Likely pathogenic 95754 rs398124308 GRCh37: 11:126144895-126144896
GRCh38: 11:126275000-126275001
37 NUBPL NM_025152.3(NUBPL):c.311T>C (p.Leu104Pro) SNV Likely pathogenic 209179 rs201430951 GRCh37: 14:32068514-32068514
GRCh38: 14:31599308-31599308
38 NDUFB3 NM_002491.3(NDUFB3):c.64T>C (p.Trp22Arg) SNV Likely pathogenic 252575 rs142609245 GRCh37: 2:201943669-201943669
GRCh38: 2:201078946-201078946
39 NDUFAF2 NM_174889.5(NDUFAF2):c.139C>T (p.Arg47Ter) SNV Likely pathogenic 1594 rs137852863 GRCh37: 5:60368963-60368963
GRCh38: 5:61073136-61073136
40 NDUFS2 NM_004550.4(NDUFS2):c.875T>C (p.Met292Thr) SNV Likely pathogenic 214793 rs150667550 GRCh37: 1:161180389-161180389
GRCh38: 1:161210599-161210599
41 NDUFS1 NM_005006.7(NDUFS1):c.845A>G (p.Asn282Ser) SNV Likely pathogenic 626278 rs1485032272 GRCh37: 2:207009643-207009643
GRCh38: 2:206144919-206144919
42 NDUFV1 NM_007103.4(NDUFV1):c.1156C>T (p.Arg386Cys) SNV Likely pathogenic 419230 rs150966634 GRCh37: 11:67379443-67379443
GRCh38: 11:67611972-67611972
43 NDUFB10 NM_004548.3(NDUFB10):c.131-442G>C SNV Likely pathogenic 873018 GRCh37:
GRCh38:
44 SLC25A10 NM_012140.5(SLC25A10):c.657C>T (p.Pro219=) SNV Likely pathogenic 446176 rs114621664 GRCh37: 17:79684843-79684843
GRCh38: 17:81717813-81717813
45 NDUFB3 NM_002491.3(NDUFB3):c.64T>C (p.Trp22Arg) SNV Likely pathogenic 252575 rs142609245 GRCh37: 2:201943669-201943669
GRCh38: 2:201078946-201078946
46 NUBPL NM_025152.3(NUBPL):c.815-27T>C SNV Likely pathogenic 50317 rs118161496 GRCh37: 14:32319298-32319298
GRCh38: 14:31850092-31850092
47 NDUFAF5 NM_024120.5(NDUFAF5):c.749G>T (p.Gly250Val) SNV Likely pathogenic 372253 rs757043077 GRCh37: 20:13789519-13789519
GRCh38: 20:13808873-13808873
48 NDUFS3 NM_004551.3(NDUFS3):c.374G>A (p.Arg125His) SNV Likely pathogenic 418381 rs138867882 GRCh37: 11:47602529-47602529
GRCh38: 11:47580977-47580977
49 NDUFV1 NM_007103.4(NDUFV1):c.166T>C (p.Ser56Pro) SNV Likely pathogenic 372715 rs201727685 GRCh37: 11:67376033-67376033
GRCh38: 11:67608562-67608562
50 NDUFV1 NM_007103.4(NDUFV1):c.383G>A (p.Arg128Gln) SNV Likely pathogenic 692023 rs778295360 GRCh37: 11:67376979-67376979
GRCh38: 11:67609508-67609508

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Complex I Deficiency, Nuclear Type 1:

72
# Symbol AA change Variation ID SNP ID
1 NDUFS4 p.Asp119His VAR_078946 rs747359752

Expression for Mitochondrial Complex I Deficiency, Nuclear Type 1

Search GEO for disease gene expression data for Mitochondrial Complex I Deficiency, Nuclear Type 1.

Pathways for Mitochondrial Complex I Deficiency, Nuclear Type 1

Pathways related to Mitochondrial Complex I Deficiency, Nuclear Type 1 according to KEGG:

36
# Name Kegg Source Accession
1 Oxidative phosphorylation hsa00190

GO Terms for Mitochondrial Complex I Deficiency, Nuclear Type 1

Cellular components related to Mitochondrial Complex I Deficiency, Nuclear Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.25 TMEM126B TIMMDC1 NDUFV2 NDUFV1 NDUFS6 NDUFS4
2 respiratory chain GO:0070469 10.03 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
3 mitochondrial respiratory chain complex I GO:0005747 9.93 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
4 mitochondrial inner membrane GO:0005743 9.89 TMEM126B TIMMDC1 NDUFV2 NDUFV1 NDUFS6 NDUFS4
5 mitochondrial membrane GO:0031966 9.67 TMEM126B TIMMDC1 NDUFAF4 MT-ND4
6 mitochondrion GO:0005739 9.58 TMEM126B TIMMDC1 NUBPL NDUFV2 NDUFV1 NDUFS6

Biological processes related to Mitochondrial Complex I Deficiency, Nuclear Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.97 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
2 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.7 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
3 electron transport chain GO:0022900 9.61 NDUFS4 NDUFB3 NDUFAF2
4 mitochondrial respiratory chain complex I assembly GO:0032981 9.58 TMEM126B TIMMDC1 NUBPL NDUFV2 NDUFV1 NDUFS6
5 reactive oxygen species metabolic process GO:0072593 9.5 NDUFS4 NDUFS1 MT-ND2
6 cellular respiration GO:0045333 9.43 NDUFS4 NDUFS1 NDUFAF2
7 mitochondrial ATP synthesis coupled electron transport GO:0042775 9.4 NDUFV1 NDUFS2
8 ATP synthesis coupled electron transport GO:0042773 9.37 NDUFS1 MT-ND4

Molecular functions related to Mitochondrial Complex I Deficiency, Nuclear Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.85 NDUFV2 NDUFV1 NDUFS2 NDUFS1 MT-ND2 FOXRED1
2 electron transfer activity GO:0009055 9.65 NDUFV2 NDUFS6 NDUFS2 NDUFS1 NDUFAF2
3 4 iron, 4 sulfur cluster binding GO:0051539 9.62 NUBPL NDUFV1 NDUFS2 NDUFS1
4 iron-sulfur cluster binding GO:0051536 9.55 NUBPL NDUFV2 NDUFV1 NDUFS2 NDUFS1
5 2 iron, 2 sulfur cluster binding GO:0051537 9.43 NDUFV2 NDUFS1
6 NADH dehydrogenase activity GO:0003954 9.4 NDUFS2 MT-ND4
7 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.36 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
8 oxidoreductase activity, acting on NAD(P)H GO:0016651 9.26 NDUFV1 NDUFS4 NDUFS2 NDUFS1

Sources for Mitochondrial Complex I Deficiency, Nuclear Type 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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