MC5DN2
MCID: MTC068
MIFTS: 32

Mitochondrial Complex V Deficiency, Nuclear Type 2 (MC5DN2)

Categories: Cardiovascular diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Mitochondrial Complex V Deficiency, Nuclear Type 2

MalaCards integrated aliases for Mitochondrial Complex V Deficiency, Nuclear Type 2:

Name: Mitochondrial Complex V Deficiency, Nuclear Type 2 57 13
Encephalocardiomyopathy, Mitochondrial, Neonatal, Due to Atp Synthase Deficiency 57 6 70
Mc5dn2 57 12 72
Mitochondrial Encephalo-Cardio-Myopathy Due to Isolated Mitochondrial Respiratory Chain Complex V Deficiency 58
Mitochondrial Encephalo-Cardio-Myopathy Due to Isolated Atp Synthase Deficiency 58
Neonatal Mitochondrial Encephalocardiomyopathy Due to Atp Synthase Deficiency 12
Mitochondrial Neonatal Encephalocardiomyopathy Due to Atp Synthase Deficiency 72
Mitochondrial Encephalo-Cardio-Myopathy Due to F1fo Atpase Deficiency 58
Mitochondrial Encephalo-Cardio-Myopathy Due to Tmem70 Deficiency 72
Tmem70-Related Mitochondrial Encephalo-Cardio-Myopathy 58
Mitochondrial Complex V Deficiency, Nuclear, Type 2 39
Mitochondrial Complex V Deficiency Nuclear Type 2 12
Mitochondrial Complex V Deficiency, Nuclear Type 2 72
Mitochondrial Complex V Deficiency, Tmem70 Type 57
Mitochondrial Complex V Deficiency Tmem70 Type 72
Mitochondrial Complex V Deficiency Type 2 72

Characteristics:

Orphanet epidemiological data:

58
tmem70-related mitochondrial encephalo-cardio-myopathy
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
early death may occur
variable features and severity
onset at birth or in utero


HPO:

31
mitochondrial complex v deficiency, nuclear type 2:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Mitochondrial Complex V Deficiency, Nuclear Type 2

UniProtKB/Swiss-Prot : 72 Mitochondrial complex V deficiency, nuclear type 2: A mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, cardiomyopathy, enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebrospinal fluid.

MalaCards based summary : Mitochondrial Complex V Deficiency, Nuclear Type 2, also known as encephalocardiomyopathy, mitochondrial, neonatal, due to atp synthase deficiency, is related to tmem70 defect and sengers syndrome. An important gene associated with Mitochondrial Complex V Deficiency, Nuclear Type 2 is TMEM70 (Transmembrane Protein 70). Affiliated tissues include heart and kidney, and related phenotypes are cataract and seizure

Disease Ontology : 12 A mitochondrial complex V (ATP synthase) deficiency that has material basis in mutation in the TMEM70 gene on chromosome 8q21.

More information from OMIM: 614052 PS604273

Related Diseases for Mitochondrial Complex V Deficiency, Nuclear Type 2

Diseases related to Mitochondrial Complex V Deficiency, Nuclear Type 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 tmem70 defect 11.7
2 sengers syndrome 11.6

Symptoms & Phenotypes for Mitochondrial Complex V Deficiency, Nuclear Type 2

Human phenotypes related to Mitochondrial Complex V Deficiency, Nuclear Type 2:

31 58 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cataract 31 occasional (7.5%) HP:0000518
2 seizure 31 occasional (7.5%) HP:0001250
3 cryptorchidism 58 31 Frequent (79-30%) HP:0000028
4 intrauterine growth retardation 58 31 Frequent (79-30%) HP:0001511
5 low-set ears 58 31 Very frequent (99-80%) HP:0000369
6 hypertrophic cardiomyopathy 58 31 Frequent (79-30%) HP:0001639
7 arrhythmia 58 31 Occasional (29-5%) HP:0011675
8 hypospadias 58 31 Frequent (79-30%) HP:0000047
9 hyperammonemia 58 31 Very frequent (99-80%) HP:0001987
10 oligohydramnios 58 31 Very frequent (99-80%) HP:0001562
11 3-methylglutaconic aciduria 58 31 Very frequent (99-80%) HP:0003535
12 seizures 58 Occasional (29-5%)
13 failure to thrive 31 HP:0001508
14 ataxia 31 HP:0001251
15 tremor 31 HP:0001337
16 hypertension 31 HP:0000822
17 muscular hypotonia 58 Very frequent (99-80%)
18 respiratory insufficiency 31 HP:0002093
19 encephalitis 58 Very frequent (99-80%)
20 global developmental delay 31 HP:0001263
21 hepatomegaly 58 Frequent (79-30%)
22 inguinal hernia 31 HP:0000023
23 wide nasal bridge 31 HP:0000431
24 umbilical hernia 31 HP:0001537
25 microcephaly 58 Very frequent (99-80%)
26 anteverted nares 31 HP:0000463
27 flexion contracture 58 Frequent (79-30%)
28 abnormal aortic valve morphology 58 Frequent (79-30%)
29 congestive heart failure 58 Frequent (79-30%)
30 flat face 31 HP:0012368
31 growth delay 58 Frequent (79-30%)
32 retrognathia 58 Frequent (79-30%)
33 wide mouth 58 Frequent (79-30%)
34 cerebral cortical atrophy 58 Frequent (79-30%)
35 long philtrum 31 HP:0000343
36 death in infancy 58 Frequent (79-30%)
37 increased serum lactate 31 HP:0002151
38 flat occiput 31 HP:0005469
39 intellectual disability, moderate 58 Very frequent (99-80%)
40 abnormal pulmonary valve morphology 58 Frequent (79-30%)
41 short philtrum 58 Very frequent (99-80%)
42 abnormality of the kidney 58 Occasional (29-5%)
43 microretrognathia 31 HP:0000308
44 camptodactyly of finger 58 Frequent (79-30%)
45 premature birth 31 HP:0001622
46 aplasia/hypoplasia of the corpus callosum 58 Frequent (79-30%)
47 moderate global developmental delay 58 Very frequent (99-80%)
48 respiratory failure 58 Frequent (79-30%)
49 encephalopathy 31 HP:0001298
50 leukoencephalopathy 31 HP:0002352

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth Other:
failure to thrive
poor growth
intrauterine growth retardation (iugr)

Head And Neck Face:
flat face
long philtrum
microretrognathia

Head And Neck Ears:
low-set ears

Laboratory Abnormalities:
increased serum lactate
hyperammonemia
3-methylglutaconic aciduria
increased serum alanine

Genitourinary External Genitalia Male:
hypospadias

Neurologic Central Nervous System:
leukoencephalopathy
psychomotor retardation
hypotonia
delayed psychomotor development
seizures (uncommon)
more
Head And Neck Nose:
broad nasal bridge
upturned nares

Growth Weight:
low birth weight

Head And Neck Eyes:
cataract (in 2 brothers)

Respiratory:
persistent pulmonary hypertension of the newborn
respiratory insufficiency at birth

Abdomen External Features:
inguinal hernia
umbilical hernia

Genitourinary Internal Genitalia Male:
cryptorchidism

Cardiovascular Heart:
hypertrophic cardiomyopathy
arrhythmias

Head And Neck Head:
flat occiput

Prenatal Manifestations Amniotic Fluid:
oligohydramnios

Metabolic Features:
lactic acidosis

Prenatal Manifestations Delivery:
premature delivery

Abdomen Gastrointestinal:
pseudoobstruction
delayed gastric emptying

Head And Neck Mouth:
thin, flat upper lip

Muscle Soft Tissue:
decreased mitochondrial complex v activity

Clinical features from OMIM®:

614052 (Updated 05-Apr-2021)

Drugs & Therapeutics for Mitochondrial Complex V Deficiency, Nuclear Type 2

Search Clinical Trials , NIH Clinical Center for Mitochondrial Complex V Deficiency, Nuclear Type 2

Genetic Tests for Mitochondrial Complex V Deficiency, Nuclear Type 2

Anatomical Context for Mitochondrial Complex V Deficiency, Nuclear Type 2

MalaCards organs/tissues related to Mitochondrial Complex V Deficiency, Nuclear Type 2:

40
Heart, Kidney

Publications for Mitochondrial Complex V Deficiency, Nuclear Type 2

Articles related to Mitochondrial Complex V Deficiency, Nuclear Type 2:

# Title Authors PMID Year
1
TMEM70 deficiency: Novel mutation and hypercitrullinemia during metabolic decompensation. 6 57
30950220 2019
2
Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients. 57 6
24485043 2014
3
TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome. 57 6
21147908 2011
4
TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy. 57 6
18953340 2008
5
The utility of whole exome sequencing in diagnosing neurological disorders in adults from a highly consanguineous population. 6
30724636 2019
6
Common and Novel TMEM70 Mutations in a Cohort of Italian Patients with Mitochondrial Encephalocardiomyopathy. 6
24740313 2015
7
ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment. 6
26550569 2015
8
Compensatory upregulation of respiratory chain complexes III and IV in isolated deficiency of ATP synthase due to TMEM70 mutation. 6
22433607 2012
9
Screening for nuclear genetic defects in the ATP synthase-associated genes TMEM70, ATP12 and ATP5E in patients with 3-methylglutaconic aciduria. 6
21815885 2011
10
Expression and processing of the TMEM70 protein. 6
20937241 2011

Variations for Mitochondrial Complex V Deficiency, Nuclear Type 2

ClinVar genetic disease variations for Mitochondrial Complex V Deficiency, Nuclear Type 2:

6 (show top 50) (show all 110)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TMEM70 TMEM70, 2-BP INS, 118GT Insertion Pathogenic 541 GRCh37:
GRCh38:
2 TMEM70 NM_017866.6(TMEM70):c.336T>A (p.Tyr112Ter) SNV Pathogenic 30957 rs1586636643 GRCh37: 8:74893409-74893409
GRCh38: 8:73981174-73981174
3 TMEM70 NM_017866.6(TMEM70):c.238C>T (p.Arg80Ter) SNV Pathogenic 30958 rs387907070 GRCh37: 8:74891018-74891018
GRCh38: 8:73978783-73978783
4 TMEM70 TMEM70, 2-BP DEL, 578CA Deletion Pathogenic 30959 GRCh37:
GRCh38:
5 TMEM70 NC_000008.11:g.(?_73976262)_(73981641_?)del Deletion Pathogenic 583679 GRCh37: 8:74888497-74893876
GRCh38: 8:73976262-73981641
6 TMEM70 NM_017866.6(TMEM70):c.378dup (p.Thr127fs) Duplication Pathogenic 488624 rs1554599411 GRCh37: 8:74893446-74893447
GRCh38: 8:73981211-73981212
7 TMEM70 NM_017866.6(TMEM70):c.317-2A>G SNV Pathogenic 540 rs183973249 GRCh37: 8:74893388-74893388
GRCh38: 8:73981153-73981153
8 TMEM70 NM_017866.6(TMEM70):c.117_118dup (p.Ser40fs) Duplication Pathogenic 203989 rs796052056 GRCh37: 8:74888632-74888633
GRCh38: 8:73976397-73976398
9 TMEM70 NM_017866.6(TMEM70):c.105dup (p.Val36fs) Duplication Likely pathogenic 807712 rs1411381518 GRCh37: 8:74888620-74888621
GRCh38: 8:73976385-73976386
10 TMEM70 NM_017866.6(TMEM70):c.2T>C (p.Met1Thr) SNV Likely pathogenic 936698 GRCh37: 8:74888518-74888518
GRCh38: 8:73976283-73976283
11 TMEM70 NM_017866.6(TMEM70):c.462C>A (p.Ile154=) SNV Conflicting interpretations of pathogenicity 363690 rs143954787 GRCh37: 8:74893535-74893535
GRCh38: 8:73981300-73981300
12 TMEM70 NM_017866.6(TMEM70):c.97C>A (p.Arg33=) SNV Conflicting interpretations of pathogenicity 380675 rs145329086 GRCh37: 8:74888613-74888613
GRCh38: 8:73976378-73976378
13 TMEM70 NM_017866.6(TMEM70):c.555T>G (p.Asn185Lys) SNV Conflicting interpretations of pathogenicity 203986 rs199655842 GRCh37: 8:74893628-74893628
GRCh38: 8:73981393-73981393
14 TMEM70 NM_017866.6(TMEM70):c.499G>A (p.Val167Ile) SNV Uncertain significance 471956 rs1554599426 GRCh37: 8:74893572-74893572
GRCh38: 8:73981337-73981337
15 TMEM70 NM_017866.6(TMEM70):c.730A>G (p.Ile244Val) SNV Uncertain significance 203981 rs151104827 GRCh37: 8:74893803-74893803
GRCh38: 8:73981568-73981568
16 TMEM70 NM_017866.6(TMEM70):c.116C>G (p.Ala39Gly) SNV Uncertain significance 203984 rs770816150 GRCh37: 8:74888632-74888632
GRCh38: 8:73976397-73976397
17 TMEM70 NM_017866.6(TMEM70):c.580G>T (p.Val194Leu) SNV Uncertain significance 936124 GRCh37: 8:74893653-74893653
GRCh38: 8:73981418-73981418
18 TMEM70 NM_017866.6(TMEM70):c.720_723del (p.Glu241fs) Deletion Uncertain significance 283424 rs746973761 GRCh37: 8:74893791-74893794
GRCh38: 8:73981556-73981559
19 TMEM70 NM_017866.6(TMEM70):c.655C>G (p.Leu219Val) SNV Uncertain significance 1029491 GRCh37: 8:74893728-74893728
GRCh38: 8:73981493-73981493
20 TMEM70 NM_017866.6(TMEM70):c.589C>A (p.Gln197Lys) SNV Uncertain significance 1037663 GRCh37: 8:74893662-74893662
GRCh38: 8:73981427-73981427
21 TMEM70 NM_017866.6(TMEM70):c.275G>T (p.Gly92Val) SNV Uncertain significance 1039048 GRCh37: 8:74891055-74891055
GRCh38: 8:73978820-73978820
22 TMEM70 NM_017866.6(TMEM70):c.533C>G (p.Thr178Ser) SNV Uncertain significance 1045574 GRCh37: 8:74893606-74893606
GRCh38: 8:73981371-73981371
23 TMEM70 NM_017866.6(TMEM70):c.578_579del (p.Thr193fs) Deletion Uncertain significance 419199 rs777501387 GRCh37: 8:74893650-74893651
GRCh38: 8:73981415-73981416
24 TMEM70 NM_017866.6(TMEM70):c.677T>C (p.Phe226Ser) SNV Uncertain significance 856002 GRCh37: 8:74893750-74893750
GRCh38: 8:73981515-73981515
25 TMEM70 NM_017866.6(TMEM70):c.554A>G (p.Asn185Ser) SNV Uncertain significance 859658 GRCh37: 8:74893627-74893627
GRCh38: 8:73981392-73981392
26 TMEM70 NM_017866.6(TMEM70):c.128G>A (p.Ser43Asn) SNV Uncertain significance 363689 rs199815125 GRCh37: 8:74888644-74888644
GRCh38: 8:73976409-73976409
27 TMEM70 NM_017866.6(TMEM70):c.718A>C (p.Lys240Gln) SNV Uncertain significance 835518 GRCh37: 8:74893791-74893791
GRCh38: 8:73981556-73981556
28 TMEM70 NM_017866.6(TMEM70):c.770A>C (p.Lys257Thr) SNV Uncertain significance 835696 GRCh37: 8:74893843-74893843
GRCh38: 8:73981608-73981608
29 TMEM70 NM_017866.6(TMEM70):c.77C>T (p.Ala26Val) SNV Uncertain significance 855087 GRCh37: 8:74888593-74888593
GRCh38: 8:73976358-73976358
30 TMEM70 NM_017866.6(TMEM70):c.769A>T (p.Lys257Ter) SNV Uncertain significance 858028 GRCh37: 8:74893842-74893842
GRCh38: 8:73981607-73981607
31 TMEM70 NM_017866.6(TMEM70):c.455C>T (p.Thr152Met) SNV Uncertain significance 203985 rs200820631 GRCh37: 8:74893528-74893528
GRCh38: 8:73981293-73981293
32 TMEM70 NM_017866.6(TMEM70):c.326G>T (p.Cys109Phe) SNV Uncertain significance 1020617 GRCh37: 8:74893399-74893399
GRCh38: 8:73981164-73981164
33 overlap with 4 genes NC_000008.10:g.(?_74888367)_(75279355_?)dup Duplication Uncertain significance 1023707 GRCh37: 8:74888367-75279355
GRCh38:
34 TMEM70 NM_017866.6(TMEM70):c.*196G>A SNV Uncertain significance 363696 rs886063101 GRCh37: 8:74894052-74894052
GRCh38: 8:73981817-73981817
35 TMEM70 NM_017866.6(TMEM70):c.500T>C (p.Val167Ala) SNV Uncertain significance 471957 rs1010253072 GRCh37: 8:74893573-74893573
GRCh38: 8:73981338-73981338
36 TMEM70 NM_017866.6(TMEM70):c.214C>T (p.Pro72Ser) SNV Uncertain significance 471955 rs143292919 GRCh37: 8:74890994-74890994
GRCh38: 8:73978759-73978759
37 TMEM70 NM_017866.6(TMEM70):c.*670T>C SNV Uncertain significance 363707 rs886063103 GRCh37: 8:74894526-74894526
GRCh38: 8:73982291-73982291
38 TMEM70 NM_017866.6(TMEM70):c.*963A>G SNV Uncertain significance 363716 rs886063104 GRCh37: 8:74894819-74894819
GRCh38: 8:73982584-73982584
39 TMEM70 NM_017866.6(TMEM70):c.*18C>T SNV Uncertain significance 363692 rs757479728 GRCh37: 8:74893874-74893874
GRCh38: 8:73981639-73981639
40 TMEM70 NM_017866.6(TMEM70):c.*942G>T SNV Uncertain significance 363715 rs531849936 GRCh37: 8:74894798-74894798
GRCh38: 8:73982563-73982563
41 TMEM70 NM_017866.6(TMEM70):c.-15C>G SNV Uncertain significance 363688 rs371606877 GRCh37: 8:74888502-74888502
GRCh38: 8:73976267-73976267
42 TMEM70 NM_017866.6(TMEM70):c.*300A>G SNV Uncertain significance 363698 rs886063102 GRCh37: 8:74894156-74894156
GRCh38: 8:73981921-73981921
43 TMEM70 NM_017866.6(TMEM70):c.*456T>G SNV Uncertain significance 363701 rs775732275 GRCh37: 8:74894312-74894312
GRCh38: 8:73982077-73982077
44 TMEM70 NM_017866.6(TMEM70):c.-39G>T SNV Uncertain significance 363686 rs200386494 GRCh37: 8:74888478-74888478
GRCh38: 8:73976243-73976243
45 TMEM70 NM_017866.6(TMEM70):c.*413T>C SNV Uncertain significance 363699 rs759034954 GRCh37: 8:74894269-74894269
GRCh38: 8:73982034-73982034
46 TMEM70 NM_017866.6(TMEM70):c.534T>C (p.Thr178=) SNV Uncertain significance 363691 rs139864454 GRCh37: 8:74893607-74893607
GRCh38: 8:73981372-73981372
47 TMEM70 NM_017866.6(TMEM70):c.*693C>T SNV Uncertain significance 363708 rs574729956 GRCh37: 8:74894549-74894549
GRCh38: 8:73982314-73982314
48 TMEM70 NM_017866.6(TMEM70):c.*942G>C SNV Uncertain significance 363714 rs531849936 GRCh37: 8:74894798-74894798
GRCh38: 8:73982563-73982563
49 TMEM70 NM_017866.6(TMEM70):c.*29G>A SNV Uncertain significance 363694 rs780620441 GRCh37: 8:74893885-74893885
GRCh38: 8:73981650-73981650
50 TMEM70 NM_017866.6(TMEM70):c.*425T>A SNV Uncertain significance 363700 rs149063225 GRCh37: 8:74894281-74894281
GRCh38: 8:73982046-73982046

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Complex V Deficiency, Nuclear Type 2:

72
# Symbol AA change Variation ID SNP ID
1 TMEM70 p.Thr210Pro VAR_068847

Expression for Mitochondrial Complex V Deficiency, Nuclear Type 2

Search GEO for disease gene expression data for Mitochondrial Complex V Deficiency, Nuclear Type 2.

Pathways for Mitochondrial Complex V Deficiency, Nuclear Type 2

GO Terms for Mitochondrial Complex V Deficiency, Nuclear Type 2

Sources for Mitochondrial Complex V Deficiency, Nuclear Type 2

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....