MC2DN1
MCID: MTC207
MIFTS: 57

Mitochondrial Complex Ii Deficiency, Nuclear Type 1 (MC2DN1)

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

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

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

Name: Mitochondrial Complex Ii Deficiency, Nuclear Type 1 57
Mitochondrial Complex Ii Deficiency 57 12 20 72 36 29 13 6 44 15 70
Succinate Coq Reductase Deficiency 57 20 72
Mc1dn2 57 12 72
Isolated Mitochondrial Respiratory Chain Complex Ii Deficiency 12 58
Mitochondrial Respiratory Chain Complex Ii Deficiency 20 39
Complex 2 Mitochondrial Respiratory Chain Deficiency 20 72
Mitochondrial Complex I Deficiency, Nuclear Type 2 57 72
Isolated Succinate-Coenzyme Q Reductase Deficiency 12 58
Isolated Succinate-Ubiquinone Reductase Deficiency 12 58
Mitochondrial Complex 1 Deficiency, Nuclear Type 2 29 6
Isolated Succinate-Coq Reductase Deficiency 12 58
Succinate Dehydrogenase Deficiency 57 20
Complex Ii Mitochondrial Respiratory Chain Deficiency 72
Nuclear Type Mitochondrial Complex I Deficiency 2 12
Isolated Succinate Dehydrogenase Deficiency 58
Sdh-Defective Infantile Leukoencephalopathy 72
Succinate-Coenzyme Q Reductase Deficiency 70
Mc2dn1 57
Mt-C2d 72

Characteristics:

Orphanet epidemiological data:

58
isolated succinate-coq reductase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in first year of life


HPO:

31
mitochondrial complex ii deficiency, nuclear type 1:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset

mitochondrial complex i deficiency, nuclear type 2:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

UniProtKB/Swiss-Prot : 72 Mitochondrial complex I deficiency, nuclear type 2: 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. MC1DN2 inheritance is autosomal recessive.
Mitochondrial complex II deficiency: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome.

MalaCards based summary : Mitochondrial Complex Ii Deficiency, Nuclear Type 1, also known as mitochondrial complex ii deficiency, is related to leigh syndrome and paraganglioma, and has symptoms including seizures, ataxia and muscle weakness. An important gene associated with Mitochondrial Complex Ii Deficiency, Nuclear Type 1 is SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A), and among its related pathways/superpathways are Citrate cycle (TCA cycle) and Oxidative phosphorylation. The drug Guadecitabine has been mentioned in the context of this disorder. Affiliated tissues include eye, skeletal muscle and brain, and related phenotypes are developmental regression and motor deterioration

Disease Ontology : 12 A mitochondrial metabolism disease characerized by a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. It has material basis in homozygous or compound heterozygous mutation in the nuclear-encoded SDHA gene on chromosome 5p, the nuclear-encoded SDHAF1 gene on chromosome 19q, or the nuclear-encoded SDHD gene on chromosome 11q23.

GARD : 20 Complex II deficiency is a 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. The signs and symptoms of mitochondrial complex II deficiency can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood. Complex II deficiency can be caused by mutations in the SDHA, SDHB, SDHD, or SDHAF1 genes. In many cases the underlying gene mutations cannot be identified. Complex II deficiency is inherited in an autosomal recessive fashion. Complex II deficiency gene mutation carriers may be at an increased risk for certain cancers.

OMIM® : 57 Mitochondrial complex II deficiency is an autosomal recessive multisystemic metabolic disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, and muscle with onset in infancy, whereas others have only isolated cardiac or muscle involvement. Measurement of complex II activity in muscle is the most reliable means of diagnosis; however, there is no clear correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin may have clinical benefit (summary by Jain-Ghai et al., 2013). Complex II, also known as succinate dehydrogenase, is part of the mitochondrial respiratory chain. (252011) (Updated 05-Apr-2021)

KEGG : 36 Mitochondrial complex II (CII, succinate dehydrogenase complex) deficiency is a rare cause of mitochondrial respiratory chain defects. CII functions in the TCA cycle and in the mitochondrial electron transport chain (ETC). Four structural subunits (SDHA, SDHB, SDHC and SDHD) and two known assembly factor genes (SDHAF1 and SDHAF2) are all nuclear-encoded. Mutations in SDHA, SDHD, and SDHAF1 have been found in patients. CII deficiency has a variable phenotype. Brain imaging is abnormal in majority of the patients and consists of leukoencephalopathy, Leigh syndrome or cerebellar atrophy.

Related Diseases for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

(show top 50) (show all 85)
# Related Disease Score Top Affiliating Genes
1 leigh syndrome 31.4 SDHD SDHC SDHB SDHAF2 SDHAF1 SDHA
2 paraganglioma 30.2 SDHD SDHC SDHB SDHAF2 SDHA
3 gastrointestinal stromal tumor 30.1 SDHD SDHC SDHB SDHA
4 hereditary paraganglioma-pheochromocytoma syndromes 30.1 SDHD SDHC SDHB SDHAF2 SDHA
5 fumarase deficiency 30.0 SDHAF1 SDHA
6 paragangliomas 1 29.9 SDHD SDHC SDHB SDHA
7 pheochromocytoma-paraganglioma 29.9 SDHD SDHC SDHB SDHA
8 glomus tumor 29.8 SDHD SDHB
9 cowden syndrome 29.8 SDHD SDHC SDHB
10 paraganglioma and gastric stromal sarcoma 29.7 SDHD SDHC SDHB SDHAF2 SDHA
11 pheochromocytoma 29.2 SDHD SDHC SDHB SDHAF3 SDHAF2 SDHA
12 mitochondrial complex iv deficiency, nuclear type 2 11.5
13 mitochondrial complex iii deficiency, nuclear type 2 11.5
14 tricarboxylic acid cycle, defect of 11.2
15 mitochondrial complex ii deficiency, nuclear type 2 11.0
16 myopathy 10.3
17 mitochondrial myopathy 10.3
18 dermis tumor 10.3 SDHD SDHA
19 sporadic pheochromocytoma/secreting paraganglioma 10.3 SDHD SDHB
20 plethora of newborn 10.3 SDHD SDHB
21 cranial nerve palsy 10.2 SDHD SDHB
22 hereditary renal cell carcinoma 10.2 SDHB SDHA
23 adrenal gland pheochromocytoma 10.2
24 autonomic nervous system benign neoplasm 10.2 SDHD SDHB
25 quadriplegia 10.2 SDHD SDHAF1 SDHA
26 spastic quadriplegia 10.2 SDHD SDHAF1 SDHA
27 peripheral nervous system benign neoplasm 10.2 SDHD SDHB
28 subglottis benign neoplasm 10.2 SDHC SDHB
29 developmental and epileptic encephalopathy 47 10.1
30 dysphagia 10.1
31 encephalopathy 10.1
32 seizure disorder 10.1
33 multiple endocrine neoplasia, type i 10.1 SDHD SDHC SDHB
34 multiple endocrine neoplasia, type iib 10.1 SDHD SDHB SDHAF2
35 neuroendocrine tumor 10.1 SDHD SDHB SDHA
36 mitochondrial disorders 10.1
37 multiple endocrine neoplasia 10.1 SDHD SDHC SDHB
38 leukodystrophy 10.1
39 spastic paraplegia 38, autosomal dominant 10.1 SDHB SDHA HTT
40 neurofibromatosis, type i 10.0 SDHD SDHC SDHB
41 kearns-sayre syndrome 10.0 SDHD SDHAF1 SDHA
42 cerebellar angioblastoma 10.0 SDHD SDHC SDHB SDHA
43 foster-kennedy syndrome 10.0 SDHD SDHC SDHAF2 SDHA
44 carney triad 10.0 SDHD SDHC SDHB SDHA
45 barth syndrome 10.0
46 dilated cardiomyopathy 10.0
47 kidney cancer 10.0
48 mesenchymal cell neoplasm 10.0
49 lactic acidosis 10.0
50 congestive heart failure 10.0

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



Diseases related to Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

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

58 31 (show top 50) (show all 83)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
2 motor deterioration 58 31 frequent (33%) Frequent (79-30%) HP:0002333
3 progressive psychomotor deterioration 58 31 frequent (33%) Frequent (79-30%) HP:0007272
4 hypertrophic cardiomyopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001639
5 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
6 easy fatigability 58 31 frequent (33%) Frequent (79-30%) HP:0003388
7 left ventricular hypertrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001712
8 weight loss 58 31 frequent (33%) Frequent (79-30%) HP:0001824
9 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
10 generalized muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003324
11 severe short stature 58 31 frequent (33%) Frequent (79-30%) HP:0003510
12 hyperactive deep tendon reflexes 58 31 frequent (33%) Frequent (79-30%) HP:0006801
13 proximal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003701
14 distal amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003693
15 hyperactive patellar reflex 58 31 frequent (33%) Frequent (79-30%) HP:0007083
16 hyperreflexia in upper limbs 58 31 frequent (33%) Frequent (79-30%) HP:0007350
17 skeletal myopathy 58 31 frequent (33%) Frequent (79-30%) HP:0003756
18 abnormal left ventricular function 31 frequent (33%) HP:0005162
19 generalized myoclonic seizure 31 frequent (33%) HP:0002123
20 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
21 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
22 intrauterine growth retardation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001511
23 irritability 58 31 occasional (7.5%) Occasional (29-5%) HP:0000737
24 moderate global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0011343
25 spastic tetraparesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001285
26 spastic paraparesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002313
27 knee flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0006380
28 generalized hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001290
29 abnormal atrioventricular conduction 58 31 occasional (7.5%) Occasional (29-5%) HP:0005150
30 frequent falls 58 31 occasional (7.5%) Occasional (29-5%) HP:0002359
31 expressive language delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0002474
32 mild microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0040196
33 lower limb hypertonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0006895
34 noncompaction cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0012817
35 focal myoclonic seizure 31 occasional (7.5%) HP:0011166
36 nystagmus 58 31 very rare (1%) Very rare (<4-1%) HP:0000639
37 blindness 58 31 very rare (1%) Very rare (<4-1%) HP:0000618
38 vesicoureteral reflux 58 31 very rare (1%) Very rare (<4-1%) HP:0000076
39 poor head control 58 31 very rare (1%) Very rare (<4-1%) HP:0002421
40 external ophthalmoplegia 58 31 very rare (1%) Very rare (<4-1%) HP:0000544
41 loss of ability to walk 58 31 very rare (1%) Very rare (<4-1%) HP:0006957
42 dementia 58 31 very rare (1%) Very rare (<4-1%) HP:0000726
43 pigmentary retinopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0000580
44 global developmental delay 31 very rare (1%) HP:0001263
45 spasticity 58 31 Frequent (79-30%) HP:0001257
46 seizures 58 Occasional (29-5%)
47 hyperreflexia 31 HP:0001347
48 ptosis 31 HP:0000508
49 dysarthria 31 HP:0001260
50 muscle weakness 31 HP:0001324

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
ataxia
cognitive impairment
more
Muscle Soft Tissue:
muscle weakness
exercise intolerance
ragged red fibers seen on muscle biopsy
hypotonia, neonatal
abnormal mitochondria with paracrystalline inclusions seen on muscle biopsy
more
Cardiovascular Heart:
hypertrophic cardiomyopathy
dilated cardiomyopathy
left ventricular noncompaction

Growth Other:
poor growth

Laboratory Abnormalities:
decreased activity of mitochondrial complex ii (succinate dehydrogenase)
mildly increased serum lactate

Head And Neck Eyes:
ptosis
nystagmus
optic atrophy
ophthalmoplegia
pigmentary retinopathy
more
Growth Height:
short stature

Skeletal:
joint contractures

Metabolic Features:
lactic acidosis may occur with stress or infection

Clinical features from OMIM®:

252011 618222 (Updated 05-Apr-2021)

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


seizures; ataxia; muscle weakness; myoclonus; ophthalmoplegia; muscle spasticity

MGI Mouse Phenotypes related to Mitochondrial Complex Ii Deficiency, Nuclear Type 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.85 COL6A2 HTT IQSEC2 MFSD8 NDUFA5 PC
2 growth/size/body region MP:0005378 9.73 COL6A2 HTT IQSEC2 NDUFS8 PCSK6 PTPMT1
3 mortality/aging MP:0010768 9.4 HTT IQSEC2 NDUFA5 NDUFS8 PC PCSK6

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

Drugs for Mitochondrial Complex Ii Deficiency, Nuclear Type 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Guadecitabine Investigational Phase 2 929901-49-5

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase II Trial of the DNA Methyl Transferase Inhibitor, SGI-110 (Guadecitabine), In Children And Adults With Wild Type GIST, Pheochromocytoma And Paraganglioma Associated With Succinate Dehydrogenase Deficiency And HLRCC-Associated Kidney Cancer Completed NCT03165721 Phase 2 SGI-110 (guadecitabine)

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

Cochrane evidence based reviews: mitochondrial complex ii deficiency

Genetic Tests for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

# Genetic test Affiliating Genes
1 Mitochondrial Complex Ii Deficiency 29 SDHA
2 Mitochondrial Complex 1 Deficiency, Nuclear Type 2 29 NDUFS8

Anatomical Context for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

40
Eye, Skeletal Muscle, Brain, Heart, Pituitary

Publications for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

(show top 50) (show all 64)
# Title Authors PMID Year
1
Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. 6 57 61
22972948 2012
2
Phenotypic variability of mitochondrial disease caused by a nuclear mutation in complex II. 57 6
16798039 2006
3
Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II. 57 6
12794685 2003
4
Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. 57 6
10746566 2000
5
Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. 57 6
7550341 1995
6
Deficiency in complex II of the respiratory chain, presenting as a leukodystrophy in two sisters with Leigh syndrome. 6 57
1492653 1992
7
Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma. 6
30877234 2019
8
Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma. 6
30050099 2019
9
Germline c.1A>C heterozygous pathogenic variant in SDHA reported for the first time in a young adult with a gastric gastrointestinal stromal tumour (GIST): a case report. 6
31413764 2019
10
Bayesian approach to determining penetrance of pathogenic SDH variants. 6
30201732 2018
11
Germline SDHA mutations in children and adults with cancer. 6
30068732 2018
12
Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide Study. 6
29177515 2018
13
Biochemical, Molecular, and Clinical Characterization of Succinate Dehydrogenase Subunit A Variants of Unknown Significance. 6
28724664 2017
14
Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention. 6
28384794 2017
15
SDHA mutated paragangliomas may be at high risk of metastasis. 6
28500238 2017
16
SDHA related tumorigenesis: a new case series and literature review for variant interpretation and pathogenicity. 6
28546994 2017
17
Expanded genetic screening panel for the Ashkenazi Jewish population. 6
26334176 2016
18
Carney triad can be (rarely) associated with germline succinate dehydrogenase defects. 6
26173966 2016
19
Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy. 6
26642834 2016
20
Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. 6
26556299 2016
21
Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients. 6
26269449 2015
22
Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum. 6
26259135 2015
23
Toward an improved definition of the genetic and tumor spectrum associated with SDH germ-line mutations. 6
25394176 2015
24
SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T). 6
25720320 2015
25
Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort. 6
25494863 2015
26
Protein-mediated assembly of succinate dehydrogenase and its cofactors. 6
25488574 2015
27
SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. 6
24781757 2015
28
SDHD immunohistochemistry: a new tool to validate SDHx mutations in pheochromocytoma/paraganglioma. 6
25405498 2015
29
A novel germline mutation in SDHA identified in a rare case of gastrointestinal stromal tumor complicated with renal cell carcinoma. 6
26722403 2015
30
Rare germline mutations identified by targeted next-generation sequencing of susceptibility genes in pheochromocytoma and paraganglioma. 6
24694336 2014
31
Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST. 6
23612575 2014
32
Germline SDHA mutation detected by next-generation sequencing in a young index patient with large paraganglioma. 6
23750034 2013
33
A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma. 6
23666964 2013
34
SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors. 6
23174939 2013
35
Overexpression of insulin-like growth factor 1 receptor and frequent mutational inactivation of SDHA in wild-type SDHB-negative gastrointestinal stromal tumors. 6
23109135 2013
36
Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors. 6
22955521 2013
37
Loss of SDHA expression identifies SDHA mutations in succinate dehydrogenase-deficient gastrointestinal stromal tumors. 6
23060355 2013
38
Complex II deficiency--a case report and review of the literature. 57
23322652 2013
39
Flavinylation and assembly of succinate dehydrogenase are dependent on the C-terminal tail of the flavoprotein subunit. 6
23043141 2012
40
SDHA loss of function mutations in a subset of young adult wild-type gastrointestinal stromal tumors. 6
22974104 2012
41
A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma. 6
22517557 2012
42
Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing. 6
22499348 2012
43
SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas. 6
21752896 2011
44
SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. 6
21505157 2011
45
Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. 6
21858060 2011
46
Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. 6
20551992 2010
47
SDHA is a tumor suppressor gene causing paraganglioma. 6
20484225 2010
48
Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA). 6
16361598 2006
49
Crystal structure of mitochondrial respiratory membrane protein complex II. 6
15989954 2005
50
Late-onset Leigh syndrome in a patient with mitochondrial complex I NDUFS8 mutations. 6
15159508 2004

Variations for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

6 (show top 50) (show all 1169)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NDUFS8 NM_002496.4(NDUFS8):c.305G>A (p.Arg102His) SNV Pathogenic 7512 rs121912638 GRCh37: 11:67800683-67800683
GRCh38: 11:68033216-68033216
2 NDUFS8 NM_002496.4(NDUFS8):c.254C>T (p.Pro85Leu) SNV Pathogenic 7513 rs121912639 GRCh37: 11:67800632-67800632
GRCh38: 11:68033165-68033165
3 NDUFS8 NM_002496.4(NDUFS8):c.413G>A (p.Arg138His) SNV Pathogenic 7514 rs111033588 GRCh37: 11:67803760-67803760
GRCh38: 11:68036293-68036293
4 NDUFS8 NM_002496.4(NDUFS8):c.476C>A (p.Ala159Asp) SNV Pathogenic 39834 rs397514617 GRCh37: 11:67803823-67803823
GRCh38: 11:68036356-68036356
5 NDUFS8 NM_002496.4(NDUFS8):c.187G>C (p.Glu63Gln) SNV Pathogenic 39835 rs397514618 GRCh37: 11:67800467-67800467
GRCh38: 11:68033000-68033000
6 SDHA NM_004168.4(SDHA):c.1A>C (p.Met1Leu) SNV Pathogenic 8744 rs1061517 GRCh37: 5:218471-218471
GRCh38: 5:218356-218356
7 SDHA NM_004168.4(SDHA):c.1664G>A (p.Gly555Glu) SNV Pathogenic 8745 rs137852768 GRCh37: 5:251453-251453
GRCh38: 5:251338-251338
8 SDHA NM_004168.4(SDHA):c.1526C>T (p.Ser509Leu) SNV Pathogenic 39586 rs397514541 GRCh37: 5:240566-240566
GRCh38: 5:240451-240451
9 SDHA NM_004168.4(SDHA):c.1754G>A (p.Arg585Gln) SNV Pathogenic 239658 rs752360961 GRCh37: 5:251543-251543
GRCh38: 5:251428-251428
10 SDHA NM_004168.4(SDHA):c.457-2_457del Deletion Pathogenic 239672 rs878854632 GRCh37: 5:225995-225997
GRCh38: 5:225880-225882
11 SDHA NM_004168.4(SDHA):c.762_770+17del Deletion Pathogenic 412346 rs1041809852 GRCh37: 5:228439-228464
GRCh38: 5:228324-228349
12 SDHA NM_004168.4(SDHA):c.1615dup (p.Ile539fs) Duplication Pathogenic 412366 rs1554001843 GRCh37: 5:251166-251167
GRCh38: 5:251051-251052
13 SDHA NM_004168.4(SDHA):c.985C>T (p.Arg329Ter) SNV Pathogenic 412328 rs771328239 GRCh37: 5:233681-233681
GRCh38: 5:233566-233566
14 SDHA NM_004168.4(SDHA):c.1468G>T (p.Glu490Ter) SNV Pathogenic 472288 rs1554000360 GRCh37: 5:240508-240508
GRCh38: 5:240393-240393
15 SDHA NM_004168.4(SDHA):c.378del (p.Thr126_Val127insTer) Deletion Pathogenic 472290 rs1553997617 GRCh37: 5:225598-225598
GRCh38: 5:225483-225483
16 SDHA NM_004168.4(SDHA):c.688del (p.Glu230fs) Deletion Pathogenic 472291 rs1553998199 GRCh37: 5:228363-228363
GRCh38: 5:228248-228248
17 SDHA NM_004168.4(SDHA):c.628C>T (p.Arg210Ter) SNV Pathogenic 539663 rs775143272 GRCh37: 5:228306-228306
GRCh38: 5:228191-228191
18 SDHA NM_004168.4(SDHA):c.722_726del (p.Asp241fs) Deletion Pathogenic 539664 rs1553998229 GRCh37: 5:228398-228402
GRCh38: 5:228283-228287
19 SDHA NM_004168.4(SDHA):c.1547dup (p.Lys517fs) Duplication Pathogenic 539642 rs1554000378 GRCh37: 5:240586-240587
GRCh38: 5:240471-240472
20 SDHA NM_004168.4(SDHA):c.1629T>G (p.Tyr543Ter) SNV Pathogenic 539643 rs747249998 GRCh37: 5:251184-251184
GRCh38: 5:251069-251069
21 SDHA NM_004168.4(SDHA):c.644_645del (p.Tyr215fs) Deletion Pathogenic 569511 rs1560989804 GRCh37: 5:228321-228322
GRCh38: 5:228206-228207
22 SDHA NM_004168.4(SDHA):c.46_52dup (p.Leu18fs) Duplication Pathogenic 574154 rs1560980939 GRCh37: 5:218510-218511
GRCh38: 5:218395-218396
23 SDHA NM_004168.4(SDHA):c.253_256dup (p.Asn86delinsIleTer) Duplication Pathogenic 576450 rs1560986132 GRCh37: 5:224576-224577
GRCh38: 5:224461-224462
24 SDHA NM_004168.4(SDHA):c.553C>T (p.Gln185Ter) SNV Pathogenic 480771 rs775827529 GRCh37: 5:226094-226094
GRCh38: 5:225979-225979
25 SDHA NM_004168.4(SDHA):c.995_996del (p.Pro332fs) Deletion Pathogenic 575469 rs1560994766 GRCh37: 5:233691-233692
GRCh38: 5:233576-233577
26 SDHA NM_004168.4(SDHA):c.2T>A (p.Met1Lys) SNV Pathogenic 582115 rs750380279 GRCh37: 5:218472-218472
GRCh38: 5:218357-218357
27 SDHA NM_004168.4(SDHA):c.880C>T (p.Gln294Ter) SNV Pathogenic 582775 rs1560992565 GRCh37: 5:231100-231100
GRCh38: 5:230985-230985
28 SDHA NM_004168.4(SDHA):c.1258C>T (p.Gln420Ter) SNV Pathogenic 639589 rs1579407009 GRCh37: 5:235452-235452
GRCh38: 5:235337-235337
29 SDHA NM_004168.4(SDHA):c.5C>A (p.Ser2Ter) SNV Pathogenic 644096 rs780064103 GRCh37: 5:218475-218475
GRCh38: 5:218360-218360
30 SDHA NM_004168.4(SDHA):c.615T>A (p.Tyr205Ter) SNV Pathogenic 230290 rs876658486 GRCh37: 5:226156-226156
GRCh38: 5:226041-226041
31 SDHA NM_004168.4(SDHA):c.1579del (p.Arg527fs) Deletion Pathogenic 653810 rs1579437839 GRCh37: 5:251133-251133
GRCh38: 5:251018-251018
32 SDHA NM_004168.4(SDHA):c.1151C>G (p.Ser384Ter) SNV Pathogenic 230877 rs151170408 GRCh37: 5:235345-235345
GRCh38: 5:235230-235230
33 SDHA NM_004168.4(SDHA):c.942_945delinsTCC (p.Glu314fs) Indel Pathogenic 657145 rs1579402188 GRCh37: 5:233638-233641
GRCh38: 5:233523-233526
34 SDHA NM_004168.4(SDHA):c.619_620delinsC (p.Ser208fs) Indel Pathogenic 660785 rs1579386206 GRCh37: 5:226160-226161
GRCh38: 5:226045-226046
35 SDHA NM_004168.4(SDHA):c.775del (p.Tyr259fs) Deletion Pathogenic 486395 rs1553998606 GRCh37: 5:230995-230995
GRCh38: 5:230880-230880
36 SDHA NM_004168.4(SDHA):c.28del (p.Leu10fs) Deletion Pathogenic 654714 rs1579369841 GRCh37: 5:218498-218498
GRCh38: 5:218383-218383
37 SDHA NM_004168.4(SDHA):c.508C>T (p.Gln170Ter) SNV Pathogenic 665061 rs1579385645 GRCh37: 5:226049-226049
GRCh38: 5:225934-225934
38 SDHA NM_004168.4(SDHA):c.1795-1G>T SNV Pathogenic 691997 rs778516878 GRCh37: 5:254507-254507
GRCh38: 5:254392-254392
39 SDHA NM_004168.4(SDHA):c.181G>T (p.Glu61Ter) SNV Pathogenic 836392 GRCh37: 5:224505-224505
GRCh38: 5:224390-224390
40 SDHA NM_004168.4(SDHA):c.83dup (p.Gly29fs) Duplication Pathogenic 836479 GRCh37: 5:223615-223616
GRCh38: 5:223500-223501
41 SDHA NM_004168.4(SDHA):c.1A>T (p.Met1Leu) SNV Pathogenic 371794 rs1061517 GRCh37: 5:218471-218471
GRCh38: 5:218356-218356
42 SDHA NM_004168.4(SDHA):c.64-2A>G SNV Pathogenic 835516 GRCh37: 5:223595-223595
GRCh38: 5:223480-223480
43 SDHA NM_004168.4(SDHA):c.1656del (p.Phe552fs) Deletion Pathogenic 839974 GRCh37: 5:251211-251211
GRCh38: 5:251096-251096
44 SDHA NM_004168.4(SDHA):c.1397dup (p.Cys467fs) Duplication Pathogenic 855920 GRCh37: 5:236678-236679
GRCh38: 5:236563-236564
45 SDHA NM_004168.4(SDHA):c.356G>A (p.Trp119Ter) SNV Pathogenic 856810 GRCh37: 5:225577-225577
GRCh38: 5:225462-225462
46 SDHA NM_004168.4(SDHA):c.468T>G (p.Tyr156Ter) SNV Pathogenic 857526 GRCh37: 5:226009-226009
GRCh38: 5:225894-225894
47 SDHA NM_004168.4(SDHA):c.1123C>T (p.Gln375Ter) SNV Pathogenic 857818 GRCh37: 5:235317-235317
GRCh38: 5:235202-235202
48 SDHA NM_004168.4(SDHA):c.484del (p.Arg162fs) Deletion Pathogenic 947042 GRCh37: 5:226025-226025
GRCh38: 5:225910-225910
49 SDHA NM_004168.4(SDHA):c.245_252del (p.Glu82fs) Deletion Pathogenic 947608 GRCh37: 5:224568-224575
GRCh38: 5:224453-224460
50 SDHA NM_004168.4(SDHA):c.267T>A (p.Cys89Ter) SNV Pathogenic 821669 rs1579381753 GRCh37: 5:224591-224591
GRCh38: 5:224476-224476

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

72
# Symbol AA change Variation ID SNP ID
1 NDUFS8 p.Pro79Leu VAR_019538 rs28939679
2 NDUFS8 p.Arg102His VAR_019539 rs121912638
3 NDUFS8 p.Glu63Gln VAR_081440 rs397514618
4 SDHA p.Gly555Glu VAR_016879 rs137852768
5 SDHAF1 p.Arg55Pro VAR_058097 rs137853193
6 SDHAF1 p.Gly57Arg VAR_058098 rs137853192
7 SDHD p.Glu69Lys VAR_074105 rs202198133
8 SDHD p.Asp92Gly VAR_074106 rs786205436

Expression for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

Pathways for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

36
# Name Kegg Source Accession
1 Citrate cycle (TCA cycle) hsa00020
2 Oxidative phosphorylation hsa00190

Pathways related to Mitochondrial Complex Ii Deficiency, Nuclear Type 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.05 SDHD SDHC SDHB SDHA NDUFS8 NDUFA5
2
Show member pathways
12.98 SDHD SDHC SDHB SDHA NDUFS8 NDUFA5
3
Show member pathways
12.35 SDHD SDHC SDHB SDHA NDUFS8 NDUFA5
4
Show member pathways
11.68 SDHD SDHC SDHB SDHA
5
Show member pathways
11.68 SDHD SDHC SDHB SDHA PC
6
Show member pathways
11.03 SDHD SDHC SDHB SDHA PC

GO Terms for Mitochondrial Complex Ii Deficiency, Nuclear Type 1

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.72 SDHAF3 SDHAF2 SDHAF1 PC NDUFS8
2 mitochondrion GO:0005739 9.7 SDHD SDHC SDHB SDHAF3 SDHAF2 SDHAF1
3 mitochondrial inner membrane GO:0005743 9.63 SDHD SDHC SDHB SDHA PTPMT1 NDUFA5
4 respiratory chain complex II GO:0045273 9.26 SDHC SDHB
5 mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) GO:0005749 8.92 SDHD SDHC SDHB SDHA

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

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.88 SDHD SDHC SDHB SDHA NDUFS8 NDUFA5
2 electron transport chain GO:0022900 9.61 SDHC SDHB SDHA
3 aerobic respiration GO:0009060 9.54 SDHC SDHB NDUFS8
4 respiratory electron transport chain GO:0022904 9.5 SDHB SDHA NDUFA5
5 succinate metabolic process GO:0006105 9.43 SDHB SDHAF3 SDHA
6 tricarboxylic acid cycle GO:0006099 9.35 SDHD SDHC SDHB SDHAF2 SDHA
7 mitochondrial respiratory chain complex II assembly GO:0034553 9.33 SDHAF3 SDHAF2 SDHAF1
8 mitochondrial electron transport, succinate to ubiquinone GO:0006121 8.92 SDHD SDHC SDHAF2 SDHA

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.32 SDHC SDHA
2 ubiquinone binding GO:0048039 9.26 SDHD SDHB
3 electron transfer activity GO:0009055 9.26 SDHD SDHC SDHB SDHA
4 succinate dehydrogenase (ubiquinone) activity GO:0008177 9.16 SDHB SDHA
5 succinate dehydrogenase activity GO:0000104 8.8 SDHD SDHC SDHA

Sources for Mitochondrial Complex Ii 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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....