COXPD6
MCID: CMB017
MIFTS: 41

Combined Oxidative Phosphorylation Deficiency 6 (COXPD6)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 6

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 6:

Name: Combined Oxidative Phosphorylation Deficiency 6 57 12 72 29 13 6 15 70
Coxpd6 57 12 72
Mitochondrial Encephalomyopathy Due to Combined Oxidative Phosphorylation Defect 6 12 58
Severe X-Linked Mitochondrial Encephalomyopathy 12 58
Mitochondrial Encephalomyopathy Due to Coxpd6 12 58
Oxidative Phosphorylation Deficiency, Combined, Type 6 39
Encephalomyopathy, Mitochondrial, X-Linked 57
Encephalomyopathy Mitochondrial X-Linked 72

Characteristics:

Orphanet epidemiological data:

58
severe x-linked mitochondrial encephalomyopathy
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: early childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
progressive disorder
onset in first year of life
two patients from 1 italian family have been reported (as of april 2010)

Inheritance:
x-linked recessive


HPO:

31
combined oxidative phosphorylation deficiency 6:
Onset and clinical course infantile onset progressive
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 6

OMIM® : 57 Combined oxidative phosphorylation deficiency-6 (COXPD6) is an X-linked recessive severe encephalomyopathic disorder with onset in utero or in infancy. Affected patients have hypotonia and severely impaired psychomotor development associated with variably decreased enzymatic activity of mitochondrial respiratory complexes in skeletal muscle or fibroblasts. More variable features may include sensorimotor neuropathy, seizures, severe muscle weakness, abnormal signals in the basal ganglia, hypertrophic cardiomyopathy, deafness, swallowing difficulties, and respiratory insufficiency. Death in childhood may occur (summary by Berger et al., 2011). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (300816) (Updated 05-Apr-2021)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 6, also known as coxpd6, is related to foot drop and spondyloepimetaphyseal dysplasia, x-linked, and has symptoms including seizures, muscle weakness and involuntary movements. An important gene associated with Combined Oxidative Phosphorylation Deficiency 6 is AIFM1 (Apoptosis Inducing Factor Mitochondria Associated 1), and among its related pathways/superpathways are Mannose type O-glycan biosynthesis and Succinylcholine Pathway, Pharmacokinetics/Pharmacodynamics. Affiliated tissues include skeletal muscle, tongue and brain, and related phenotypes are delayed speech and language development and skeletal muscle atrophy

Disease Ontology : 12 A combined oxidative phosphorylation deficiency that has material basis in hemizygous mutation in AIFM1 on chromosome Xq26.1.

UniProtKB/Swiss-Prot : 72 Combined oxidative phosphorylation deficiency 6: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 6

Diseases related to Combined Oxidative Phosphorylation Deficiency 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)
# Related Disease Score Top Affiliating Genes
1 foot drop 10.3 RAB33A AIFM1
2 spondyloepimetaphyseal dysplasia, x-linked 10.3 RAB33A AIFM1
3 spondyloepimetaphyseal dysplasia, x-linked, with hypomyelinating leukodystrophy 10.3 RAB33A AIFM1
4 charcot-marie-tooth disease, x-linked recessive, 4, with or without cerebellar ataxia 10.3 RAB33A AIFM1
5 hypomyelinating leukodystrophy 10.2 RAB33A PRODH AIFM1
6 muscular dystrophy, congenital, 1b 10.2 RXYLT1 B3GALNT2
7 mitochondrial encephalomyopathy 10.1
8 mitochondrial dna-associated leigh syndrome and narp 10.1
9 nuclear gene-encoded leigh syndrome spectrum 10.1
10 congenital muscular dystrophy-dystroglycanopathy type a 10.1 RXYLT1 B3GALNT2
11 congenital muscular dystrophy-dystroglycanopathy type a3 10.1 RXYLT1 B3GALNT2
12 codas syndrome 10.1 LONP1 HSPA9
13 cobblestone lissencephaly 10.1 RXYLT1 B3GALNT2
14 auditory neuropathy spectrum disorder 10.0 RAB33A PJVK AIFM1
15 opitz-kaveggia syndrome 9.9 VCX3A BRWD3
16 muscular dystrophy-dystroglycanopathy , type a, 4 9.8 RXYLT1 B3GALNT2
17 slow-channel congenital myasthenic syndrome 9.8 CHRND CHRNB1
18 postsynaptic congenital myasthenic syndromes 9.8 CHRND CHRNB1
19 myasthenic syndrome, congenital, 13 9.8 CHRND CHRNB1
20 myasthenic syndrome, congenital, 14 9.8 CHRND CHRNB1
21 myasthenic syndrome, congenital, 1a, slow-channel 9.7 CHRND CHRNB1
22 charcot-marie-tooth disease x-linked recessive 4 9.7 VCX3A RAB33A PJVK LONP1 AIFM1
23 neuromuscular junction disease 9.6 CHRND CHRNB1
24 fetal akinesia deformation sequence 1 9.6 PRODH CHRND CHRNB1
25 deafness, x-linked 5, with peripheral neuropathy 9.5 VCX3A RAB33A PJVK HS6ST2 AIFM1
26 ptosis 9.5 LONP1 CHRND CHRNB1

Graphical network of the top 20 diseases related to Combined Oxidative Phosphorylation Deficiency 6:



Diseases related to Combined Oxidative Phosphorylation Deficiency 6

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 6

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 6:

58 31 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed speech and language development 58 31 hallmark (90%) Very frequent (99-80%) HP:0000750
2 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003202
3 areflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001284
4 severe muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0006829
5 moderate global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011343
6 generalized muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003324
7 generalized hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001290
8 increased variability in muscle fiber diameter 58 31 hallmark (90%) Very frequent (99-80%) HP:0003557
9 abnormal corpus striatum morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0010994
10 sensory axonal neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003390
11 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
12 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
13 irritability 58 31 frequent (33%) Frequent (79-30%) HP:0000737
14 increased serum lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002151
15 increased csf lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002490
16 increased serum pyruvate 58 31 frequent (33%) Frequent (79-30%) HP:0003542
17 respiratory distress 58 31 frequent (33%) Frequent (79-30%) HP:0002098
18 hypokinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002375
19 increased connective tissue 58 31 frequent (33%) Frequent (79-30%) HP:0009025
20 tongue fasciculations 58 31 frequent (33%) Frequent (79-30%) HP:0001308
21 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
22 tetraplegia 31 HP:0002445
23 global developmental delay 31 HP:0001263
24 respiratory insufficiency due to muscle weakness 31 HP:0002747
25 ragged-red muscle fibers 31 HP:0003200
26 involuntary movements 58 Frequent (79-30%)
27 peripheral neuropathy 58 Very frequent (99-80%)
28 fasciculations 31 HP:0002380
29 hyporeflexia 31 HP:0001265
30 psychomotor retardation 31 HP:0025356
31 polyneuropathy 31 HP:0001271
32 abnormality of the basal ganglia 31 HP:0002134
33 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
tetraplegia
involuntary movements
fasciculations
hypotonia
more
Respiratory:
respiratory insufficiency due to muscle weakness

Laboratory Abnormalities:
increased lactate in serum and csf
increased pyruvate in serum and csf

Muscle Soft Tissue:
muscle weakness
muscle atrophy
mitochondrial dna depletion (20 to 35% of normal) seen on skeletal muscle biopsy
decreased activity of multiple mitochondrial respiratory complex enzymes
ragged-red fibers
more
Neurologic Peripheral Nervous System:
sensory and motor axonal polyneuropathy

Clinical features from OMIM®:

300816 (Updated 05-Apr-2021)

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 6:


seizures; muscle weakness; involuntary movements; muscular fasciculation

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 6

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 6

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 6

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 6:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 6 29 AIFM1

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 6

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 6:

40
Skeletal Muscle, Tongue, Brain

Publications for Combined Oxidative Phosphorylation Deficiency 6

Articles related to Combined Oxidative Phosphorylation Deficiency 6:

# Title Authors PMID Year
1
A novel AIFM1 mutation expands the phenotype to an infantile motor neuron disease. 6 57
26173962 2016
2
From ventriculomegaly to severe muscular atrophy: expansion of the clinical spectrum related to mutations in AIFM1. 57 6
25583628 2015
3
Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing. 6 57
22019070 2011
4
Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. 6 57
20362274 2010
5
Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease. 61
27102849 2017

Variations for Combined Oxidative Phosphorylation Deficiency 6

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 6:

6 (show all 36)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1436A>G (p.Gln479Arg) SNV Pathogenic 369972 rs1057516211 GRCh37: X:129267300-129267300
GRCh38: X:130133325-130133325
2 RAB33A , AIFM1 NM_004208.4(AIFM1):c.923G>A (p.Gly308Glu) SNV Pathogenic 732658 rs1603224226 GRCh37: X:129272612-129272612
GRCh38: X:130138637-130138637
3 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1013G>A (p.Gly338Glu) SNV Pathogenic 732668 rs1603223152 GRCh37: X:129271115-129271115
GRCh38: X:130137140-130137140
4 RAB33A , AIFM1 NM_004208.4(AIFM1):c.727G>T (p.Val243Leu) SNV Pathogenic 732675 rs1603225138 GRCh37: X:129274562-129274562
GRCh38: X:130140587-130140587
5 RAB33A , AIFM1 NM_004208.4(AIFM1):c.603_605del (p.Arg201del) Deletion Pathogenic 11546 rs387906500 GRCh37: X:129281468-129281470
GRCh38: X:130147493-130147495
6 RAB33A , AIFM1 NM_004208.4(AIFM1):c.506C>T (p.Pro169Leu) SNV Likely pathogenic 982823 GRCh37: X:129281567-129281567
GRCh38: X:130147592-130147592
7 RAB33A , AIFM1 NM_004208.4(AIFM1):c.452G>A (p.Arg151Gln) SNV Uncertain significance 214082 rs752742151 GRCh37: X:129281749-129281749
GRCh38: X:130147774-130147774
8 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1355T>C (p.Val452Ala) SNV Uncertain significance 912874 GRCh37: X:129267381-129267381
GRCh38: X:130133406-130133406
9 RAB33A , AIFM1 NM_004208.4(AIFM1):c.147G>C (p.Gln49His) SNV Uncertain significance 1028702 GRCh37: X:129290537-129290537
GRCh38: X:130156563-130156563
10 RAB33A , AIFM1 NM_004208.4(AIFM1):c.-185G>A SNV Uncertain significance 367897 rs770317876 GRCh37: X:129299815-129299815
GRCh38: X:130165841-130165841
11 RAB33A , AIFM1 NM_004208.4(AIFM1):c.170C>G (p.Ser57Cys) SNV Uncertain significance 445310 rs201711375 GRCh37: X:129290514-129290514
GRCh38: X:130156540-130156540
12 RAB33A , AIFM1 NM_004208.4(AIFM1):c.*49C>T SNV Uncertain significance 367888 rs1057515766 GRCh37: X:129263483-129263483
GRCh38: X:130129508-130129508
13 RAB33A , AIFM1 NM_004208.4(AIFM1):c.-140C>G SNV Uncertain significance 367895 rs770737305 GRCh37: X:129299770-129299770
GRCh38: X:130165796-130165796
14 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1647A>G (p.Ala549=) SNV Uncertain significance 367889 rs1057515767 GRCh37: X:129264068-129264068
GRCh38: X:130130093-130130093
15 RAB33A , AIFM1 NM_004208.4(AIFM1):c.858+13T>G SNV Uncertain significance 913253 GRCh37: X:129273757-129273757
GRCh38: X:130139782-130139782
16 RAB33A , AIFM1 NM_004208.4(AIFM1):c.697-4C>T SNV Uncertain significance 913254 GRCh37: X:129274596-129274596
GRCh38: X:130140621-130140621
17 RAB33A , AIFM1 NM_004208.4(AIFM1):c.248A>G (p.Tyr83Cys) SNV Uncertain significance 914370 GRCh37: X:129290436-129290436
GRCh38: X:130156462-130156462
18 RAB33A , AIFM1 NM_004208.4(AIFM1):c.-90G>C SNV Uncertain significance 914371 GRCh37: X:129299720-129299720
GRCh38: X:130165746-130165746
19 RAB33A , AIFM1 NM_004208.4(AIFM1):c.366A>G (p.Glu122=) SNV Likely benign 367891 rs756883753 GRCh37: X:129281835-129281835
GRCh38: X:130147860-130147860
20 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1047C>T (p.Ser349=) SNV Likely benign 214080 rs781350745 GRCh37: X:129271081-129271081
GRCh38: X:130137106-130137106
21 RAB33A , AIFM1 NM_004208.4(AIFM1):c.340G>A (p.Ala114Thr) SNV Likely benign 857026 GRCh37: X:129283453-129283453
GRCh38: X:130149478-130149478
22 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1644G>A (p.Pro548=) SNV Likely benign 377456 rs150821143 GRCh37: X:129264071-129264071
GRCh38: X:130130096-130130096
23 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1416T>C (p.Ala472=) SNV Benign 136324 rs141324245 GRCh37: X:129267320-129267320
GRCh38: X:130133345-130133345
24 RAB33A , AIFM1 NM_004208.4(AIFM1):c.273T>C (p.Asp91=) SNV Benign 367892 rs1139851 GRCh37: X:129283520-129283520
GRCh38: X:130149545-130149545
25 RAB33A , AIFM1 NM_004208.4(AIFM1):c.606-15C>T SNV Benign 367890 rs191297808 GRCh37: X:129279559-129279559
GRCh38: X:130145584-130145584
26 RAB33A , AIFM1 NM_004208.4(AIFM1):c.72C>T (p.Cys24=) SNV Benign 367894 rs373609902 GRCh37: X:129299559-129299559
GRCh38: X:130165585-130165585
27 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1227T>G (p.Thr409=) SNV Benign 543932 rs61730898 GRCh37: X:129270098-129270098
GRCh38: X:130136123-130136123
28 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1833T>C (p.His611=) SNV Benign 136325 rs73556209 GRCh37: X:129263541-129263541
GRCh38: X:130129566-130129566
29 RAB33A , AIFM1 NM_004208.4(AIFM1):c.996A>G (p.Gln332=) SNV Benign 136322 rs12007545 GRCh37: X:129271132-129271132
GRCh38: X:130137157-130137157
30 RAB33A , AIFM1 NM_004208.4(AIFM1):c.103C>T (p.Pro35Ser) SNV Benign 136326 rs61730896 GRCh37: X:129299528-129299528
GRCh38: X:130165554-130165554
31 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1329C>T (p.Tyr443=) SNV Benign 136323 rs143792929 GRCh37: X:129267407-129267407
GRCh38: X:130133432-130133432
32 RAB33A , AIFM1 NM_004208.4(AIFM1):c.918C>T (p.Ile306=) SNV Benign 136320 rs12014115 GRCh37: X:129272617-129272617
GRCh38: X:130138642-130138642
33 RAB33A , AIFM1 NM_004208.4(AIFM1):c.597A>G (p.Lys199=) SNV Benign 913255 GRCh37: X:129281476-129281476
GRCh38: X:130147501-130147501
34 RAB33A , AIFM1 NM_004208.4(AIFM1):c.-165G>A SNV Benign 367896 rs759015293 GRCh37: X:129299795-129299795
GRCh38: X:130165821-130165821
35 RAB33A , AIFM1 NM_004208.4(AIFM1):c.262A>G (p.Met88Val) SNV Benign 367893 rs750098055 GRCh37: X:129283531-129283531
GRCh38: X:130149556-130149556
36 RAB33A , AIFM1 NM_004208.4(AIFM1):c.968-14T>A SNV Benign 912875 GRCh37: X:129271174-129271174
GRCh38: X:130137199-130137199

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 6:

72
# Symbol AA change Variation ID SNP ID
1 AIFM1 p.Gly308Glu VAR_067334
2 AIFM1 p.Val243Leu VAR_072791
3 AIFM1 p.Gly338Glu VAR_083068

Expression for Combined Oxidative Phosphorylation Deficiency 6

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 6.

Pathways for Combined Oxidative Phosphorylation Deficiency 6

Pathways related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.32 RXYLT1 B3GALNT2
2 9.7 CHRND CHRNB1

GO Terms for Combined Oxidative Phosphorylation Deficiency 6

Cellular components related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.73 TMEM126A TMEM11 PRODH LONP1 HSPA9 AIFM1
2 mitochondrial inner membrane GO:0005743 9.46 TMEM126A TMEM11 PRODH AIFM1
3 integral component of postsynaptic specialization membrane GO:0099060 8.96 CHRND CHRNB1
4 acetylcholine-gated channel complex GO:0005892 8.62 CHRND CHRNB1

Biological processes related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 skeletal muscle contraction GO:0003009 8.96 CHRND CHRNB1
2 inner mitochondrial membrane organization GO:0007007 8.62 TMEM11 HSPA9

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential GO:1904315 9.32 CHRND CHRNB1
2 FAD binding GO:0071949 9.26 PRODH AIFM1
3 ligand-gated ion channel activity GO:0015276 9.16 CHRND CHRNB1
4 acetylcholine-gated cation-selective channel activity GO:0022848 8.96 CHRND CHRNB1
5 acetylcholine binding GO:0042166 8.62 CHRND CHRNB1

Sources for Combined Oxidative Phosphorylation Deficiency 6

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
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