COQ10D4
MCID: CNZ005
MIFTS: 34

Coenzyme Q10 Deficiency, Primary, 4 (COQ10D4)

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

Aliases & Classifications for Coenzyme Q10 Deficiency, Primary, 4

MalaCards integrated aliases for Coenzyme Q10 Deficiency, Primary, 4:

Name: Coenzyme Q10 Deficiency, Primary, 4 57 12 75 29 13 6
Scar9 57 12 53 59 75
Spinocerebellar Ataxia, Autosomal Recessive 9 57 12 73
Autosomal Recessive Cerebellar Ataxia Type 2 53 59 75
Coq10d4 57 12 75
Arca2 53 59 75
Autosomal Recessive Ataxia Due to Coenzyme Q10 Deficiency 53 59
Autosomal Recessive Ataxia Due to Ubiquinone Deficiency 53 59
Autosomal Recessive Spinocerebellar Ataxia Type 9 53 59
Primary Coenzyme Q10 Deficiency 4 12 15
Ataxia, Spinocerebellar, Autosomal Recessive, Type 9 ) 40
Spinocerebellar Ataxia, Autosomal Recessive 9; Scar9 57
Autosomal Recessive Spinocerebellar Ataxia 9 53
Spinocerebellar Ataxia Autosomal Recessive 9 75
Coenzyme Q10 Deficiency, Primary, Type 4 ) 40

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive ataxia due to ubiquinone deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in early to late childhood
seizures and cognitive involvement are variable findings
oral supplementation with ubiquinone does not result in major clinical improvement


HPO:

32
coenzyme q10 deficiency, primary, 4:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Coenzyme Q10 Deficiency, Primary, 4

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 139485Disease definitionThis syndrome is characterised by childhood-onset progressive ataxia and cerebellar atrophy.EpidemiologyPrevalence is unknown.Clinical descriptionExercise intolerance with elevated lactate levels and mild intellectual deficit may also be present.EtiologyThe syndrome is caused by ubiquinone deficiency. Mutations in the ADCK3/CABC1 gene have been detected in affected individuals. This gene is already known to play a role in ubiquinone biosynthesis in yeast.Genetic counselingThe syndrome is transmitted as an autosomal recessivetrait.Visit the Orphanet disease page for more resources.

MalaCards based summary : Coenzyme Q10 Deficiency, Primary, 4, also known as scar9, is related to multiple acyl-coa dehydrogenase deficiency and aceruloplasminemia, and has symptoms including cerebellar ataxia An important gene associated with Coenzyme Q10 Deficiency, Primary, 4 is COQ8A (Coenzyme Q8A), and among its related pathways/superpathways is Ubiquinol biosynthesis. Related phenotypes are seizures and tremor

Disease Ontology : 12 A primary coenzyme Q10 deficiency that has material basis in an autosomal recessive mutation of ADCK3 on chromosome 1q42.13.

OMIM : 57 Primary coenzyme Q10 deficiency-4 is an autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Some affected individuals develop seizures and have mild mental impairment, indicating variable severity. Oral coenzyme Q10 supplementation does not result in significant improvement of neurologic symptoms (summary by Mollet et al., 2008 and Lagier-Tourenne et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426). (612016)

UniProtKB/Swiss-Prot : 75 Coenzyme Q10 deficiency, primary, 4: An autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Patient manifest gait ataxia and cerebellar atrophy with slow progression. Additional features include brisk tendon reflexes and Hoffmann sign, variable psychomotor retardation and variable seizures.

Related Diseases for Coenzyme Q10 Deficiency, Primary, 4

Diseases related to Coenzyme Q10 Deficiency, Primary, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 multiple acyl-coa dehydrogenase deficiency 9.9 COQ8A COQ9
2 aceruloplasminemia 9.7 COQ8A SYP
3 coenzyme q10 deficiency disease 8.9 COQ3 COQ5 COQ7 COQ8A COQ9 SYP

Symptoms & Phenotypes for Coenzyme Q10 Deficiency, Primary, 4

Symptoms via clinical synopsis from OMIM:

57
Neurologic Peripheral Nervous System:
hyperreflexia

Metabolic Features:
lactic acidosis

Neurologic Central Nervous System:
cerebellar atrophy
cerebellar ataxia
tremor (less common)
pyramidal signs (less common)
myoclonic jerks (less common)
more
Skeletal Feet:
pes cavus
talus valgus

Muscle Soft Tissue:
proximal muscle weakness
exercise intolerance
hypotonia
decreased coenzyme q
decreased activity of respiratory complex ii+iii
more
Laboratory Abnormalities:
increased serum and csf lactate


Clinical features from OMIM:

612016

Human phenotypes related to Coenzyme Q10 Deficiency, Primary, 4:

59 32 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 frequent (33%) Occasional (29-5%) HP:0001250
2 tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0001337
3 hyperreflexia 59 32 Occasional (29-5%) HP:0001347
4 developmental regression 59 32 frequent (33%) Frequent (79-30%) HP:0002376
5 hearing impairment 59 32 very rare (1%) Very rare (<4-1%) HP:0000365
6 emg abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0003457
7 strabismus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000486
8 myoclonus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001336
9 neurodevelopmental delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0012758
10 dystonia 59 32 very rare (1%) Very rare (<4-1%) HP:0001332
11 increased serum lactate 59 32 occasional (7.5%) Occasional (29-5%) HP:0002151
12 lactic acidosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003128
13 intellectual disability, moderate 59 32 frequent (33%) Frequent (79-30%) HP:0002342
14 progressive cerebellar ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002073
15 gynecomastia 59 32 very rare (1%) Very rare (<4-1%) HP:0000771
16 proximal muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0003701
17 cerebellar atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001272
18 exercise intolerance 59 32 frequent (33%) Frequent (79-30%) HP:0003546
19 brisk reflexes 59 32 frequent (33%) Frequent (79-30%) HP:0001348
20 talipes cavus equinovarus 59 32 frequent (33%) Frequent (79-30%) HP:0004696
21 central hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0011398
22 focal t2 hypointense basal ganglia lesion 59 32 frequent (33%) Frequent (79-30%) HP:0012752
23 increased csf lactate 59 32 occasional (7.5%) Occasional (29-5%) HP:0002490
24 intellectual disability 32 occasional (7.5%) HP:0001249
25 ataxia 32 HP:0001251
26 abnormal pyramidal signs 59 Occasional (29-5%)
27 global developmental delay 32 occasional (7.5%) HP:0001263
28 pes cavus 32 HP:0001761
29 increased intramyocellular lipid droplets 32 HP:0012240
30 generalized hypotonia 32 HP:0001290
31 abnormal pyramidal sign 32 occasional (7.5%) HP:0007256

UMLS symptoms related to Coenzyme Q10 Deficiency, Primary, 4:


cerebellar ataxia

Drugs & Therapeutics for Coenzyme Q10 Deficiency, Primary, 4

Search Clinical Trials , NIH Clinical Center for Coenzyme Q10 Deficiency, Primary, 4

Genetic Tests for Coenzyme Q10 Deficiency, Primary, 4

Genetic tests related to Coenzyme Q10 Deficiency, Primary, 4:

# Genetic test Affiliating Genes
1 Coenzyme Q10 Deficiency, Primary, 4 29 COQ8A

Anatomical Context for Coenzyme Q10 Deficiency, Primary, 4

Publications for Coenzyme Q10 Deficiency, Primary, 4

Variations for Coenzyme Q10 Deficiency, Primary, 4

UniProtKB/Swiss-Prot genetic disease variations for Coenzyme Q10 Deficiency, Primary, 4:

75 (show all 12)
# Symbol AA change Variation ID SNP ID
1 COQ8A p.Arg213Trp VAR_044402 rs119468005
2 COQ8A p.Gly272Asp VAR_044403 rs119468006
3 COQ8A p.Gly272Val VAR_044404 rs119468006
4 COQ8A p.Tyr514Cys VAR_044405 rs119468008
5 COQ8A p.Gly549Ser VAR_044406 rs119468009
6 COQ8A p.Glu551Lys VAR_044407 rs119468004
7 COQ8A p.Arg271Cys VAR_072622 rs145034527
8 COQ8A p.Arg299Trp VAR_072623 rs201908721
9 COQ8A p.Ala304Thr VAR_072624 rs778798354
10 COQ8A p.Ala304Val VAR_072625 rs748118737
11 COQ8A p.Tyr429Cys VAR_072626 rs144147839
12 COQ8A p.Pro602Arg VAR_072627 rs61995958

ClinVar genetic disease variations for Coenzyme Q10 Deficiency, Primary, 4:

6 (show top 50) (show all 80)
# Gene Variation Type Significance SNP ID Assembly Location
1 COQ8A NM_020247.4(COQ8A): c.1651G> A (p.Glu551Lys) single nucleotide variant Pathogenic rs119468004 GRCh37 Chromosome 1, 227173033: 227173033
2 COQ8A NM_020247.4(COQ8A): c.1651G> A (p.Glu551Lys) single nucleotide variant Pathogenic rs119468004 GRCh38 Chromosome 1, 226985332: 226985332
3 COQ8A NM_020247.4(COQ8A): c.637C> T (p.Arg213Trp) single nucleotide variant Pathogenic rs119468005 GRCh37 Chromosome 1, 227153420: 227153420
4 COQ8A NM_020247.4(COQ8A): c.637C> T (p.Arg213Trp) single nucleotide variant Pathogenic rs119468005 GRCh38 Chromosome 1, 226965719: 226965719
5 COQ8A NM_020247.4(COQ8A): c.815G> T (p.Gly272Val) single nucleotide variant Pathogenic rs119468006 GRCh37 Chromosome 1, 227169812: 227169812
6 COQ8A NM_020247.4(COQ8A): c.815G> T (p.Gly272Val) single nucleotide variant Pathogenic rs119468006 GRCh38 Chromosome 1, 226982111: 226982111
7 COQ8A NM_020247.4(COQ8A): c.815G> A (p.Gly272Asp) single nucleotide variant Pathogenic rs119468006 GRCh37 Chromosome 1, 227169812: 227169812
8 COQ8A NM_020247.4(COQ8A): c.815G> A (p.Gly272Asp) single nucleotide variant Pathogenic rs119468006 GRCh38 Chromosome 1, 226982111: 226982111
9 COQ8A NM_020247.4(COQ8A): c.1813dupG (p.Glu605Glyfs) duplication Pathogenic rs387906298 GRCh37 Chromosome 1, 227174307: 227174307
10 COQ8A NM_020247.4(COQ8A): c.1813dupG (p.Glu605Glyfs) duplication Pathogenic rs387906298 GRCh38 Chromosome 1, 226986606: 226986606
11 COQ8A NM_020247.4(COQ8A): c.1398+2T> C single nucleotide variant Pathogenic rs606231138 GRCh38 Chromosome 1, 226984237: 226984237
12 COQ8A NM_020247.4(COQ8A): c.1398+2T> C single nucleotide variant Pathogenic rs606231138 GRCh37 Chromosome 1, 227171938: 227171938
13 COQ8A NM_020247.4(COQ8A): c.500_521del22insTTG (p.Gln167Leufs) indel Pathogenic rs606231139 GRCh38 Chromosome 1, 226965322: 226965343
14 COQ8A NM_020247.4(COQ8A): c.500_521del22insTTG (p.Gln167Leufs) indel Pathogenic rs606231139 GRCh37 Chromosome 1, 227153023: 227153044
15 COQ8A NM_020247.4(COQ8A): c.1541A> G (p.Tyr514Cys) single nucleotide variant Pathogenic rs119468008 GRCh37 Chromosome 1, 227172611: 227172611
16 COQ8A NM_020247.4(COQ8A): c.1541A> G (p.Tyr514Cys) single nucleotide variant Pathogenic rs119468008 GRCh38 Chromosome 1, 226984910: 226984910
17 COQ8A NM_020247.4(COQ8A): c.1750_1752delACC (p.Thr584del) deletion Pathogenic rs387906299 GRCh37 Chromosome 1, 227174244: 227174246
18 COQ8A NM_020247.4(COQ8A): c.1750_1752delACC (p.Thr584del) deletion Pathogenic rs387906299 GRCh38 Chromosome 1, 226986543: 226986545
19 COQ8A NM_020247.4(COQ8A): c.993C> T (p.Phe331=) single nucleotide variant Conflicting interpretations of pathogenicity rs41303129 GRCh37 Chromosome 1, 227170648: 227170648
20 COQ8A NM_020247.4(COQ8A): c.993C> T (p.Phe331=) single nucleotide variant Conflicting interpretations of pathogenicity rs41303129 GRCh38 Chromosome 1, 226982947: 226982947
21 COQ8A NM_020247.4(COQ8A): c.1645G> A (p.Gly549Ser) single nucleotide variant Pathogenic rs119468009 GRCh37 Chromosome 1, 227173027: 227173027
22 COQ8A NM_020247.4(COQ8A): c.1645G> A (p.Gly549Ser) single nucleotide variant Pathogenic rs119468009 GRCh38 Chromosome 1, 226985326: 226985326
23 COQ8A NM_020247.4(COQ8A): c.117G> A (p.Ala39=) single nucleotide variant Benign rs11549708 GRCh37 Chromosome 1, 227149203: 227149203
24 COQ8A NM_020247.4(COQ8A): c.117G> A (p.Ala39=) single nucleotide variant Benign rs11549708 GRCh38 Chromosome 1, 226961502: 226961502
25 COQ8A NM_020247.4(COQ8A): c.1440C> T (p.Phe480=) single nucleotide variant Benign rs12593 GRCh37 Chromosome 1, 227172290: 227172290
26 COQ8A NM_020247.4(COQ8A): c.1440C> T (p.Phe480=) single nucleotide variant Benign rs12593 GRCh38 Chromosome 1, 226984589: 226984589
27 COQ8A NM_020247.4(COQ8A): c.1716T> C (p.Ser572=) single nucleotide variant Benign rs3738725 GRCh37 Chromosome 1, 227174210: 227174210
28 COQ8A NM_020247.4(COQ8A): c.1716T> C (p.Ser572=) single nucleotide variant Benign rs3738725 GRCh38 Chromosome 1, 226986509: 226986509
29 COQ8A NM_020247.4(COQ8A): c.63G> A (p.Ala21=) single nucleotide variant Conflicting interpretations of pathogenicity rs11549709 GRCh37 Chromosome 1, 227149149: 227149149
30 COQ8A NM_020247.4(COQ8A): c.63G> A (p.Ala21=) single nucleotide variant Conflicting interpretations of pathogenicity rs11549709 GRCh38 Chromosome 1, 226961448: 226961448
31 COQ8A NM_020247.4(COQ8A): c.1053C> T (p.Gly351=) single nucleotide variant Benign/Likely benign rs55958233 GRCh37 Chromosome 1, 227170708: 227170708
32 COQ8A NM_020247.4(COQ8A): c.1053C> T (p.Gly351=) single nucleotide variant Benign/Likely benign rs55958233 GRCh38 Chromosome 1, 226983007: 226983007
33 COQ8A NM_020247.4(COQ8A): c.1185C> T (p.Ile395=) single nucleotide variant Benign rs17849927 GRCh37 Chromosome 1, 227171484: 227171484
34 COQ8A NM_020247.4(COQ8A): c.1185C> T (p.Ile395=) single nucleotide variant Benign rs17849927 GRCh38 Chromosome 1, 226983783: 226983783
35 COQ8A NM_020247.4(COQ8A): c.1334_1335delCA (p.Thr445Argfs) deletion Pathogenic rs797045217 GRCh37 Chromosome 1, 227171872: 227171873
36 COQ8A NM_020247.4(COQ8A): c.1334_1335delCA (p.Thr445Argfs) deletion Pathogenic rs797045217 GRCh38 Chromosome 1, 226984171: 226984172
37 COQ8A NM_020247.4(COQ8A): c.1532C> T (p.Thr511Met) single nucleotide variant Likely pathogenic rs578189699 GRCh37 Chromosome 1, 227172602: 227172602
38 COQ8A NM_020247.4(COQ8A): c.1532C> T (p.Thr511Met) single nucleotide variant Likely pathogenic rs578189699 GRCh38 Chromosome 1, 226984901: 226984901
39 COQ8A NM_020247.4(COQ8A): c.1844dupG (p.Ser616Leufs) duplication Pathogenic rs863223885 GRCh37 Chromosome 1, 227174338: 227174338
40 COQ8A NM_020247.4(COQ8A): c.1844dupG (p.Ser616Leufs) duplication Pathogenic rs863223885 GRCh38 Chromosome 1, 226986637: 226986637
41 COQ8A NM_020247.4(COQ8A): c.1042C> T (p.Arg348Ter) single nucleotide variant Pathogenic rs771578775 GRCh37 Chromosome 1, 227170697: 227170697
42 COQ8A NM_020247.4(COQ8A): c.1042C> T (p.Arg348Ter) single nucleotide variant Pathogenic rs771578775 GRCh38 Chromosome 1, 226982996: 226982996
43 COQ8A NM_020247.4(COQ8A): c.1007delT (p.Phe336Serfs) deletion Likely pathogenic rs1085307053 GRCh37 Chromosome 1, 227170662: 227170662
44 COQ8A NM_020247.4(COQ8A): c.1007delT (p.Phe336Serfs) deletion Likely pathogenic rs1085307053 GRCh38 Chromosome 1, 226982961: 226982961
45 COQ8A NM_020247.4(COQ8A): c.638_645delGGCTGGCC (p.Arg213Glnfs) deletion Pathogenic rs886042265 GRCh37 Chromosome 1, 227153421: 227153428
46 COQ8A NM_020247.4(COQ8A): c.638_645delGGCTGGCC (p.Arg213Glnfs) deletion Pathogenic rs886042265 GRCh38 Chromosome 1, 226965720: 226965727
47 COQ8A NM_020247.4(COQ8A): c.1742dupA (p.Ser582Glufs) duplication Pathogenic rs886043382 GRCh37 Chromosome 1, 227174236: 227174236
48 COQ8A NM_020247.4(COQ8A): c.1742dupA (p.Ser582Glufs) duplication Pathogenic rs886043382 GRCh38 Chromosome 1, 226986535: 226986535
49 COQ8A NM_020247.4(COQ8A): c.811C> T (p.Arg271Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs145034527 GRCh38 Chromosome 1, 226982107: 226982107
50 COQ8A NM_020247.4(COQ8A): c.811C> T (p.Arg271Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs145034527 GRCh37 Chromosome 1, 227169808: 227169808

Expression for Coenzyme Q10 Deficiency, Primary, 4

Search GEO for disease gene expression data for Coenzyme Q10 Deficiency, Primary, 4.

Pathways for Coenzyme Q10 Deficiency, Primary, 4

Pathways related to Coenzyme Q10 Deficiency, Primary, 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.29 COQ3 COQ5 COQ7 COQ9

GO Terms for Coenzyme Q10 Deficiency, Primary, 4

Cellular components related to Coenzyme Q10 Deficiency, Primary, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.55 COQ3 COQ5 COQ7 COQ8A COQ9
2 mitochondrial inner membrane GO:0005743 9.26 COQ3 COQ5 COQ7 COQ9
3 extrinsic component of mitochondrial inner membrane GO:0031314 8.92 COQ3 COQ5 COQ7 COQ8A

Biological processes related to Coenzyme Q10 Deficiency, Primary, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ubiquinone biosynthetic process GO:0006744 9.02 COQ3 COQ5 COQ7 COQ8A COQ9
2 methylation GO:0032259 8.96 COQ3 COQ5

Molecular functions related to Coenzyme Q10 Deficiency, Primary, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 methyltransferase activity GO:0008168 8.62 COQ3 COQ5

Sources for Coenzyme Q10 Deficiency, Primary, 4

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