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 56 73 29 6
Mitochondrial Complex I Deficiency 56 12 52 25 73 36 29 54 6 43 15 39
Nadh:q(1) Oxidoreductase Deficiency 56 52 25 73
Isolated Mitochondrial Respiratory Chain Complex I Deficiency 12 52 58
Isolated Nadh-Coenzyme Q Reductase Deficiency 12 52 58
Isolated Nadh-Ubiquinone Reductase Deficiency 12 52 58
Isolated Nadh-Coq Reductase Deficiency 12 52 58
Nadh-Coenzyme Q Reductase Deficiency 56 25 73
Mitochondrial Nadh Dehydrogenase Component of Complex I, Deficiency of 56 52
Isolated Complex I Deficiency 52 58
Mc1dn1 56 73
Deficiency of Mitochondrial Nadh Dehydrogenase Component of Complex I 73
Complex I, Mitochondrial Respiratory Chain, Deficiency of 13
Complex 1 Mitochondrial Respiratory Chain Deficiency 52
Complex I Mitochondrial Respiratory Chain Deficiency 73
Nadh:ubiquinone Oxidoreductase Deficiency 73
Nadh Coenzyme Q Reductase Deficiency 52

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:

56
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

Genetics Home Reference : 25 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 leigh syndrome and mitochondrial disorders, 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 liver, eye 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.

NIH Rare Diseases : 52 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 : 56 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)

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 : 73 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 116)
# Related Disease Score Top Affiliating Genes
1 leigh syndrome 34.2 NUBPL NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2
2 mitochondrial disorders 31.8 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1 NDUFB3
3 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 31.7 NDUFV2 NDUFB3 NDUFAF2 NDUFAF1 NDUFA1 MT-ND4
4 mitochondrial myopathy 31.7 NDUFV1 NDUFA1 MT-ND4 MT-ND2
5 mitochondrial metabolism disease 31.6 NUBPL NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2
6 mitochondrial encephalomyopathy 31.5 NDUFV1 NDUFS4 NDUFS1 NDUFA1 MT-ND4 MT-ND2
7 leukodystrophy 30.9 NUBPL NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2
8 leber optic atrophy 30.8 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
9 optic nerve disease 30.8 NDUFA1 MT-ND4 MT-ND2
10 visual epilepsy 30.7 NDUFAF5 NDUFAF4 NDUFA11 FOXRED1
11 hereditary optic neuropathy 30.4 MT-ND4 MT-ND2
12 mitochondrial complex i deficiency, nuclear type 20 12.9
13 mitochondrial complex i deficiency, nuclear type 2 12.9
14 mitochondrial complex i deficiency, nuclear type 4 12.9
15 mitochondrial complex i deficiency, nuclear type 6 12.9
16 mitochondrial complex i deficiency, nuclear type 8 12.9
17 mitochondrial complex i deficiency, nuclear type 9 12.9
18 mitochondrial complex i deficiency, nuclear type 14 12.9
19 mitochondrial complex i deficiency, nuclear type 25 12.9
20 mitochondrial complex i deficiency, nuclear type 27 12.9
21 mitochondrial complex i deficiency, nuclear type 32 12.9
22 mitochondrial complex i deficiency, nuclear type 33 12.9
23 mitochondrial complex i deficiency, mitochondrial type 1 12.9
24 mitochondrial complex i deficiency, nuclear type 12 12.8
25 mitochondrial complex i deficiency, nuclear type 30 12.8
26 mitochondrial complex i deficiency, nuclear type 7 12.8
27 mitochondrial complex i deficiency, nuclear type 10 12.8
28 mitochondrial complex i deficiency, nuclear type 11 12.8
29 mitochondrial complex i deficiency, nuclear type 13 12.8
30 mitochondrial complex i deficiency, nuclear type 15 12.8
31 mitochondrial complex i deficiency, nuclear type 16 12.8
32 mitochondrial complex i deficiency, nuclear type 17 12.8
33 mitochondrial complex i deficiency, nuclear type 18 12.8
34 mitochondrial complex i deficiency, nuclear type 19 12.8
35 mitochondrial complex i deficiency, nuclear type 21 12.8
36 mitochondrial complex i deficiency, nuclear type 22 12.8
37 mitochondrial complex i deficiency, nuclear type 23 12.8
38 mitochondrial complex i deficiency, nuclear type 24 12.8
39 mitochondrial complex i deficiency, nuclear type 26 12.8
40 mitochondrial complex i deficiency, nuclear type 28 12.8
41 mitochondrial complex i deficiency, nuclear type 29 12.8
42 mitochondrial complex i deficiency, nuclear type 31 12.8
43 obsolete: fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex i deficiency 12.5
44 mitochondrial complex v deficiency, nuclear type 1 12.4
45 mitochondrial complex iii deficiency, nuclear type 1 12.2
46 nephronophthisis-like nephropathy 1 11.3
47 leigh syndrome with leukodystrophy 10.8 NDUFV2 NDUFV1 NDUFS4 NDUFS2 NDUFS1 NDUFAF5
48 cardiomyopathy, infantile histiocytoid 10.7 NDUFS2 NDUFB11 NDUFAF2 NDUFA1
49 spinal cord dermoid cyst 10.7 NDUFS4 NDUFS2
50 leigh syndrome with cardiomyopathy 10.6 NDUFS2 NDUFAF3

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 57)
# 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 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
7 respiratory insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002093
8 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
9 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
10 intrauterine growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001511
11 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
12 vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002013
13 hypertrophic cardiomyopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001639
14 hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001943
15 strabismus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000486
16 lactic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0003128
17 mitochondrial myopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003737
18 paroxysmal involuntary eye movements 58 31 hallmark (90%) Very frequent (99-80%) HP:0007704
19 optic neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001138
20 lethargy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001254
21 optic disc pallor 58 31 hallmark (90%) Very frequent (99-80%) HP:0000543
22 abnormal mitochondria in muscle tissue 58 31 hallmark (90%) Very frequent (99-80%) HP:0008316
23 encephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001298
24 increased serum pyruvate 58 31 hallmark (90%) Very frequent (99-80%) HP:0003542
25 proximal tubulopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000114
26 poor eye contact 58 31 hallmark (90%) Very frequent (99-80%) HP:0000817
27 leukoencephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002352
28 leukodystrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002415
29 poor head control 58 31 hallmark (90%) Very frequent (99-80%) HP:0002421
30 increased csf lactate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002490
31 focal t2 hyperintense brainstem lesion 58 31 hallmark (90%) Very frequent (99-80%) HP:0012748
32 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
33 feeding difficulties 58 31 occasional (7.5%) Occasional (29-5%) HP:0011968
34 microcephaly 58 31 very rare (1%) Occasional (29-5%) HP:0000252
35 blindness 58 31 occasional (7.5%) Occasional (29-5%) HP:0000618
36 fetal distress 58 31 occasional (7.5%) Occasional (29-5%) HP:0025116
37 seizures 31 HP:0001250
38 spasticity 31 HP:0001257
39 hyperreflexia 31 HP:0001347
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 generalized hypotonia 31 HP:0001290
46 growth delay 31 HP:0001510
47 babinski sign 31 HP:0003487
48 respiratory failure 31 HP:0002878
49 hepatic failure 31 HP:0001399
50 coma 31 HP:0001259

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
ataxia
hyporeflexia
lethargy
cerebellar atrophy
more
Head And Neck Eyes:
ptosis
nystagmus
blindness
strabismus
optic neuropathy
more
Respiratory:
respiratory insufficiency
respiratory failure

Abdomen Gastrointestinal:
vomiting
poor feeding

Metabolic Features:
hypoglycemia
lactic acidosis

Head And Neck Ears:
sensorineural deafness
auditory neuropathy

Growth Other:
failure to thrive
growth retardation

Muscle Soft Tissue:
muscle weakness
hypotonia

Abdomen Liver:
hepatomegaly

Cardiovascular Heart:
hypertrophic cardiomyopathy

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

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 33)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 10.37 NDUFA1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-115 10.37 NDUFA1 NDUFS1 NDUFV1 NDUFV2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-120 10.37 NDUFS1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-122 10.37 NDUFA1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-125 10.37 NDUFA1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-133 10.37 NDUFS1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-147 10.37 NDUFA1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-16 10.37 NDUFS1 NDUFV2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-161 10.37 NDUFA11
10 Increased shRNA abundance (Z-score > 2) GR00366-A-164 10.37 NDUFS1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-166 10.37 NDUFS1 NDUFV1 NDUFA11
12 Increased shRNA abundance (Z-score > 2) GR00366-A-180 10.37 NDUFA1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-19 10.37 NDUFA11
14 Increased shRNA abundance (Z-score > 2) GR00366-A-214 10.37 NDUFV2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-29 10.37 NDUFV2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-4 10.37 NDUFS1
17 Increased shRNA abundance (Z-score > 2) GR00366-A-57 10.37 NDUFA1 NDUFS1 NDUFV1 NDUFV2 NDUFA11
18 Increased shRNA abundance (Z-score > 2) GR00366-A-78 10.37 NDUFV1
19 Decreased viability GR00106-A-0 10.23 NDUFV2
20 Decreased viability GR00381-A-1 10.23 NDUFAF1 NDUFAF5 NDUFV2
21 Decreased viability GR00402-S-2 10.23 FOXRED1 MT-ND2 MT-ND4 NDUFA1 NDUFA11 NDUFA13
22 Decreased shRNA abundance (Z-score < -2) GR00366-A-11 10.13 NDUFA11
23 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.13 NDUFA11 NDUFS1 NDUFV1
24 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 10.13 NDUFS1
25 Decreased shRNA abundance (Z-score < -2) GR00366-A-195 10.13 NDUFV1
26 Decreased shRNA abundance (Z-score < -2) GR00366-A-206 10.13 NDUFA11 NDUFS1 NDUFV1
27 Decreased shRNA abundance (Z-score < -2) GR00366-A-209 10.13 NDUFA11
28 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10.13 NDUFS1 NDUFV1
29 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10.13 NDUFS1
30 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 10.13 NDUFV1
31 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 10.13 NDUFA11
32 Decreased shRNA abundance GR00297-A 9.87 NDUFA1 NDUFA11 NDUFA13 NDUFS1 NDUFS2 NDUFV1
33 no effect GR00402-S-1 9.62 FOXRED1 MT-ND2 MT-ND4 NDUFA1 NDUFA11 NDUFA13

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

Anatomical Context for Mitochondrial Complex I Deficiency, Nuclear Type 1

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

40
Liver, Eye, Brain, Heart, Skeletal Muscle, Kidney, Skin

Publications for Mitochondrial Complex I Deficiency, Nuclear Type 1

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

(show top 50) (show all 152)
# Title Authors PMID Year
1
Functional characterization of the c.462delA mutation in the NDUFS4 subunit gene of mitochondrial complex I. 56 6
24020637 2014
2
A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family. 56 6
19107570 2008
3
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. 56 6
12616398 2003
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. 56 6
11181577 2001
5
Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene. 56 6
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. 56 6
9463323 1998
7
Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts. 54 61 56
10393702 1999
8
Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing. 61 56
22499348 2012
9
NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency. 61 56
15372108 2004
10
Familial mitochondrial complex I deficiency with an abnormal mitochondrial encoded protein. 61 56
2512443 1989
11
Characterization of clinically identified mutations in NDUFV1, the flavin-binding subunit of respiratory complex I, using a yeast model system. 6
26345448 2015
12
Heterozygous mutation in the X chromosomal NDUFA1 gene in a girl with complex I deficiency. 6
21596602 2011
13
Respiratory chain complex I deficiency caused by mitochondrial DNA mutations. 56
21364701 2011
14
A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency. 56
20972245 2011
15
A novel NDUFA1 mutation leads to a progressive mitochondrial complex I-specific neurodegenerative disease. 6
19185523 2009
16
C6ORF66 is an assembly factor of mitochondrial complex I. 6
18179882 2008
17
Nonsense mutations in mitochondrial DNA associated with myalgia and exercise intolerance. 6
15781840 2005
18
Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome. 56
14729820 2004
19
De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency. 56
14705112 2004
20
Late-onset encephalopathy associated with a C11777A mutation of mitochondrial DNA. 6
12707444 2003
21
Paternal inheritance of mitochondrial DNA. 6
12192017 2002
22
Respiratory chain complex I deficiency. 56
11579423 2001
23
Isolated complex I deficiency in children: clinical, biochemical and genetic aspects. 56
10649489 2000
24
Human mitochondrial complex I in health and disease. 56
10330338 1999
25
Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. 6
10080174 1999
26
Fate of microinjected spermatid mitochondria in the mouse oocyte and embryo. 6
9854792 1998
27
A high rate (20%-30%) of parental consanguinity in cytochrome-oxidase deficiency. 56
9683589 1998
28
Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect. 56
9593934 1998
29
New familial mitochondrial encephalopathy with macrocephaly, cardiomyopathy, and complex I deficiency. 56
9382480 1997
30
NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings. 56
8892026 1996
31
Human diseases with defects in oxidative phosphorylation. 1. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies. 56
7867654 1995
32
Paternal inheritance of mitochondrial DNA in mice. 6
1857422 1991
33
Congenital deficiency of a 20-kDa subunit of mitochondrial complex I in fibroblasts. 56
1903590 1991
34
Familial NADH: Q1 oxidoreductase (complex I) deficiency: variable expression and possible treatment. 56
2512441 1989
35
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. 56
3110216 1987
36
Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I. 56
3100577 1987
37
Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis. 56
6432847 1984
38
Mapping of the genes of some components of the electron transport chain (complex I) on the X chromosome of mammals. 56
6819642 1982
39
Biochemical and genetic characterization of respiration-deficient mutants of Chinese hamster cells with a Gal- phenotype. 56
7292258 1981
40
Hamster cell mutants unable to grow on galactose and exhibiting an overlapping complementation pattern are defective in the electron transport chain. 56
7240234 1981
41
Mitochondrial myopathy. Biochemical studies revealing a deficiency of NADH--cytochrome b reductase activity. 56
7229653 1981
42
A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity. 56
521828 1979
43
Respiration-deficient Chinese hamster cell mutants: biochemical characterization. 56
494059 1979
44
Respiration-deficient Chinese hamster cell mutants: genetic characterization. 56
483122 1979
45
A respiration-deficient Chinese hamster cell line with a defect in NADH-coenzyme Q reductase. 56
947896 1976
46
The selection of Chinese hamster cells deficient in oxidative energy metabolism. 56
1027147 1976
47
Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I deficiency. 54 61
19384974 2009
48
Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease. 54 61
19463981 2009
49
Mitochondrial complex I deficiency in GDAP1-related autosomal dominant Charcot-Marie-Tooth disease (CMT2K). 54 61
19089472 2009
50
Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. 54 61
19336460 2009

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 533) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NDUFB11 NM_019056.6(NDUFB11):c.262C>T (p.Arg88Ter)SNV Pathogenic 190302 rs786205225 X:47002089-47002089 X:47142690-47142690
2 NDUFAF4 NM_014165.4(NDUFAF4):c.194T>C (p.Leu65Pro)SNV Pathogenic 790 rs63751061 6:97344666-97344666 6:96896790-96896790
3 NDUFS4 NM_002495.4(NDUFS4):c.466_470dup (p.Lys158fs)duplication Pathogenic 6887 rs1445075330 5:52978987-52978988 5:53683157-53683158
4 NDUFS4 NM_002495.4(NDUFS4):c.291del (p.Lys96_Trp97insTer)deletion Pathogenic 6888 rs121908985 5:52942175-52942175 5:53646345-53646345
5 NDUFS4 NM_002495.4(NDUFS4):c.316C>T (p.Arg106Ter)SNV Pathogenic 6889 rs104893898 5:52942201-52942201 5:53646371-53646371
6 NDUFS4 NM_002495.4(NDUFS4):c.44G>A (p.Trp15Ter)SNV Pathogenic 6890 rs104893899 5:52856536-52856536 5:53560706-53560706
7 MT-ND4 m.11777C>ASNV Pathogenic 9711 rs28384199 MT:11777-11777 MT:11777-11777
8 MT-ND2 m.5132_5133delAAdeletion Pathogenic 9719 rs199476116 MT:5132-5133 MT:5132-5133
9 MT-ND2 m.4810G>ASNV Pathogenic 9720 rs267606888 MT:4810-4810 MT:4810-4810
10 NDUFS4 NM_002495.4(NDUFS4):c.462del (p.Lys154fs)deletion Pathogenic 40257 rs587776949 5:52978982-52978982 5:53683152-53683152
11 NDUFA13 NM_015965.7(NDUFA13):c.170G>A (p.Arg57His)SNV Pathogenic 132643 rs752513525 19:19637066-19637066 19:19526257-19526257
12 NDUFV1 NM_007103.4(NDUFV1):c.1118T>C (p.Phe373Ser)SNV Pathogenic 431452 rs1135402749 11:67379405-67379405 11:67611934-67611934
13 NDUFS4 NM_002495.4(NDUFS4):c.99-1G>ASNV Pathogenic 496165 rs376281345 5:52899281-52899281 5:53603451-53603451
14 NDUFS1 NM_005006.7(NDUFS1):c.64C>T (p.Arg22Ter)SNV Pathogenic 626277 rs750971390 2:207017232-207017232 2:206152508-206152508
15 NDUFV1 NM_007103.4(NDUFV1):c.1162+4A>CSNV Pathogenic/Likely pathogenic 372716 rs199683937 11:67379453-67379453 11:67611982-67611982
16 FOXRED1 NM_017547.4(FOXRED1):c.406C>T (p.Arg136Trp)SNV Pathogenic/Likely pathogenic 372745 rs373075574 11:126142963-126142963 11:126273068-126273068
17 NDUFV1 NM_007103.4(NDUFV1):c.1268C>T (p.Thr423Met)SNV Pathogenic/Likely pathogenic 14056 rs121913659 11:67379696-67379696 11:67612225-67612225
18 NDUFAF2 NM_174889.5(NDUFAF2):c.139C>T (p.Arg47Ter)SNV Pathogenic/Likely pathogenic 1594 rs137852863 5:60368963-60368963 5:61073136-61073136
19 NUBPL NM_025152.3(NUBPL):c.311T>C (p.Leu104Pro)SNV Pathogenic/Likely pathogenic 209179 rs201430951 14:32068514-32068514 14:31599308-31599308
20 NDUFB3 NM_002491.3(NDUFB3):c.64T>C (p.Trp22Arg)SNV Pathogenic/Likely pathogenic 252575 rs142609245 2:201943669-201943669 2:201078946-201078946
21 NDUFS3 NM_004551.3(NDUFS3):c.374G>A (p.Arg125His)SNV Likely pathogenic 418381 rs138867882 11:47602529-47602529 11:47580977-47580977
22 SLC25A10 NM_012140.5(SLC25A10):c.304A>T (p.Lys102Ter)SNV Likely pathogenic 446175 rs1555703272 17:79682598-79682598 17:81715568-81715568
23 NDUFAF5 NM_024120.5(NDUFAF5):c.749G>T (p.Gly250Val)SNV Likely pathogenic 372253 rs757043077 20:13789519-13789519 20:13808873-13808873
24 NDUFV1 NM_007103.4(NDUFV1):c.166T>C (p.Ser56Pro)SNV Likely pathogenic 372715 rs201727685 11:67376033-67376033 11:67608562-67608562
25 FOXRED1 NM_017547.4(FOXRED1):c.632G>C (p.Gly211Ala)SNV Likely pathogenic 522718 rs536400690 11:126145222-126145222 11:126275327-126275327
26 NDUFS3 NM_004551.3(NDUFS3):c.596G>A (p.Arg199Gln)SNV Likely pathogenic 523006 rs771783839 11:47603989-47603989 11:47582437-47582437
27 NDUFV1 NM_007103.4(NDUFV1):c.383G>A (p.Arg128Gln)SNV Likely pathogenic 692023 11:67376979-67376979 11:67609508-67609508
28 NDUFS1 NM_005006.7(NDUFS1):c.845A>G (p.Asn282Ser)SNV Likely pathogenic 626278 rs1485032272 2:207009643-207009643 2:206144919-206144919
29 NDUFS8 NM_002496.4(NDUFS8):c.299C>T (p.Ala100Val)SNV Conflicting interpretations of pathogenicity 305767 rs748754134 11:67800677-67800677 11:68033210-68033210
30 NUBPL NM_025152.3(NUBPL):c.639C>T (p.Ile213=)SNV Conflicting interpretations of pathogenicity 313029 rs35330765 14:32295866-32295866 14:31826660-31826660
31 NDUFS3 NM_004551.3(NDUFS3):c.783T>C (p.Pro261=)SNV Conflicting interpretations of pathogenicity 304999 rs117981655 11:47606021-47606021 11:47584469-47584469
32 NDUFV1 NM_007103.4(NDUFV1):c.366G>A (p.Pro122=)SNV Conflicting interpretations of pathogenicity 305744 rs140445386 11:67376962-67376962 11:67609491-67609491
33 NDUFV1 NM_007103.4(NDUFV1):c.819C>T (p.Thr273=)SNV Conflicting interpretations of pathogenicity 305749 rs150859374 11:67378584-67378584 11:67611113-67611113
34 NDUFV1 NM_007103.4(NDUFV1):c.843T>C (p.His281=)SNV Conflicting interpretations of pathogenicity 305750 rs766555879 11:67378608-67378608 11:67611137-67611137
35 NDUFV1 NM_007103.4(NDUFV1):c.1075C>T (p.Arg359Cys)SNV Conflicting interpretations of pathogenicity 305753 rs142499054 11:67379035-67379035 11:67611564-67611564
36 NDUFS8 , TCIRG1 NM_002496.4(NDUFS8):c.*40A>GSNV Conflicting interpretations of pathogenicity 305776 rs61329983 11:67804100-67804100 11:68036633-68036633
37 NDUFS8 NM_002496.4(NDUFS8):c.459C>T (p.Cys153=)SNV Conflicting interpretations of pathogenicity 305768 rs149201273 11:67803806-67803806 11:68036339-68036339
38 NDUFS8 NM_002496.4(NDUFS8):c.502-10C>TSNV Conflicting interpretations of pathogenicity 305771 rs369961682 11:67803919-67803919 11:68036452-68036452
39 NDUFS8 NM_002496.4(NDUFS8):c.597C>T (p.Ile199=)SNV Conflicting interpretations of pathogenicity 305772 rs1804688 11:67804024-67804024 11:68036557-68036557
40 NDUFV1 NM_007103.4(NDUFV1):c.1309-9C>TSNV Conflicting interpretations of pathogenicity 305756 rs374581520 11:67379834-67379834 11:67612363-67612363
41 NDUFV1 NM_007103.4(NDUFV1):c.205C>T (p.Leu69=)SNV Conflicting interpretations of pathogenicity 305740 rs199543483 11:67376072-67376072 11:67608601-67608601
42 NDUFS8 NM_002496.4(NDUFS8):c.502-13C>TSNV Conflicting interpretations of pathogenicity 305770 rs199793417 11:67803916-67803916 11:68036449-68036449
43 NDUFS3 NM_004551.3(NDUFS3):c.91T>C (p.Leu31=)SNV Conflicting interpretations of pathogenicity 304993 rs770306617 11:47600844-47600844 11:47579292-47579292
44 NUBPL NM_025152.3(NUBPL):c.-7C>TSNV Conflicting interpretations of pathogenicity 313018 rs201073307 14:32030639-32030639 14:31561433-31561433
45 NDUFS7 NM_024407.5(NDUFS7):c.270C>T (p.Ala90=)SNV Conflicting interpretations of pathogenicity 328337 rs375120743 19:1390911-1390911 19:1390912-1390912
46 NUBPL NM_025152.3(NUBPL):c.285C>T (p.Asn95=)SNV Conflicting interpretations of pathogenicity 313022 rs373232503 14:32034248-32034248 14:31565042-31565042
47 NUBPL NM_025152.3(NUBPL):c.-13A>GSNV Conflicting interpretations of pathogenicity 313017 rs754769393 14:32030633-32030633 14:31561427-31561427
48 NDUFV2 NM_021074.5(NDUFV2):c.510T>C (p.Thr170=)SNV Conflicting interpretations of pathogenicity 327879 rs201074358 18:9124912-9124912 18:9124914-9124914
49 NDUFV2 NM_021074.5(NDUFV2):c.546C>T (p.Asn182=)SNV Conflicting interpretations of pathogenicity 327880 rs143576401 18:9124948-9124948 18:9124950-9124950
50 NUBPL NM_025152.3(NUBPL):c.77G>T (p.Gly26Val)SNV Conflicting interpretations of pathogenicity 282798 rs77539990 14:32030722-32030722 14:31561516-31561516

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

73
# 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 10.28 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
2 respiratory chain GO:0070469 10.1 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
3 mitochondrial respiratory chain complex I GO:0005747 10.03 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
4 mitochondrion GO:0005739 9.89 NUBPL NDUFV2 NDUFV1 NDUFS4 NDUFS2 NDUFS1
5 mitochondrial matrix GO:0005759 9.71 NUBPL NDUFS2 NDUFS1 NDUFAF1
6 mitochondrial membrane GO:0031966 9.67 NDUFAF4 NDUFA13 NDUFA1 MT-ND4
7 mitochondrial inner membrane GO:0005743 9.6 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1

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 mitochondrial electron transport, NADH to ubiquinone GO:0006120 10 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
2 oxidation-reduction process GO:0055114 9.83 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
3 reactive oxygen species metabolic process GO:0072593 9.65 NDUFS4 NDUFS1 NDUFAF2 NDUFA13 MT-ND2
4 mitochondrial respiratory chain complex I assembly GO:0032981 9.62 NUBPL NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2
5 cellular respiration GO:0045333 9.5 NDUFS4 NDUFS1 NDUFAF2
6 mitochondrion morphogenesis GO:0070584 9.46 NUBPL NDUFS6
7 respiratory electron transport chain GO:0022904 9.43 NDUFS6 NDUFAF2
8 mitochondrial ATP synthesis coupled electron transport GO:0042775 9.4 NDUFV1 NDUFS2
9 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 9.95 NDUFV2 NDUFV1 NDUFS2 NDUFS1 NDUFAF5 MT-ND2
2 electron transfer activity GO:0009055 9.72 NDUFV2 NDUFS6 NDUFS2 NDUFS1 NDUFAF2
3 4 iron, 4 sulfur cluster binding GO:0051539 9.67 NUBPL NDUFV1 NDUFS2 NDUFS1
4 iron-sulfur cluster binding GO:0051536 9.65 NUBPL NDUFV2 NDUFV1 NDUFS2 NDUFS1
5 NAD binding GO:0051287 9.46 NDUFV1 NDUFS2
6 oxidoreductase activity, acting on NAD(P)H GO:0016651 9.46 NDUFV1 NDUFS4 NDUFS2 NDUFS1
7 2 iron, 2 sulfur cluster binding GO:0051537 9.43 NDUFV2 NDUFS1
8 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.4 NDUFV2 NDUFV1 NDUFS6 NDUFS4 NDUFS2 NDUFS1
9 NADH dehydrogenase activity GO:0003954 9.26 NDUFV2 NDUFS2 NDUFA13 MT-ND4

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
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
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43 MeSH
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45 MGI
48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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