OPA5
MCID: OPT024
MIFTS: 39

Optic Atrophy 5 (OPA5)

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

Aliases & Classifications for Optic Atrophy 5

MalaCards integrated aliases for Optic Atrophy 5:

Name: Optic Atrophy 5 57 12 20 72 29 13 6 15 70
Opa5 57 12 72
Atrophy, Optic, Type 5 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
onset in 1st to 3rd decade of life
three unrelated french families have been reported (last curated november 2017)


HPO:

31
optic atrophy 5:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:



External Ids:

Disease Ontology 12 DOID:0111438
OMIM® 57 610708
OMIM Phenotypic Series 57 PS165500
MeSH 44 D015418
MedGen 41 C1853139
UMLS 70 C1853139

Summaries for Optic Atrophy 5

UniProtKB/Swiss-Prot : 72 Optic atrophy 5: A form of optic atrophy, a disease characterized by progressive visual loss in association with a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA5 is an autosomal dominant non-syndromic form that manifests as slowly progressive visual loss with variable onset from the first to third decades. Additional ocular abnormalities may include central scotoma and dyschromatopsia.

MalaCards based summary : Optic Atrophy 5, also known as opa5, is related to myopathy, lactic acidosis, and sideroblastic anemia 2 and myopathy, lactic acidosis, and sideroblastic anemia. An important gene associated with Optic Atrophy 5 is DNM1L (Dynamin 1 Like), and among its related pathways/superpathways are Glucose / Energy Metabolism and Spinocerebellar ataxia. Affiliated tissues include eye, retina and pancreas, and related phenotypes are optic atrophy and central scotoma

Disease Ontology : 12 An optic atrophy characterized by degeneration of retinal ganglion cells resulting in slowly progressive visual loss with variable onset from the first to third decades that has material basis in heterozygous of mutation in DNM1L on chromosome 12p11.21.

OMIM® : 57 OPA5 is an autosomal dominant form of nonsyndromic optic atrophy, manifest as slowly progressive visual loss with variable onset from the first to third decades. Additional ocular abnormalities may include central scotoma and color vision defects. The pathogenesis is related to defective mitochondrial fission (summary by Gerber et al., 2017). For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500). (610708) (Updated 20-May-2021)

Related Diseases for Optic Atrophy 5

Diseases in the Primary Optic Atrophy family:

Optic Atrophy 3, Autosomal Dominant Optic Atrophy 1
Optic Atrophy 6 Optic Atrophy 2
Optic Atrophy 4 Optic Atrophy 5
Optic Atrophy 9 Optic Atrophy 8
Optic Atrophy 11 Optic Atrophy 12

Diseases related to Optic Atrophy 5 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 54)
# Related Disease Score Top Affiliating Genes
1 myopathy, lactic acidosis, and sideroblastic anemia 2 10.3 YARS2 DNM1L
2 myopathy, lactic acidosis, and sideroblastic anemia 10.3 YARS2 DNM1L
3 optic atrophy 6 10.3 TMEM126A OPA3
4 optic atrophy 2 10.2 TMEM126A OPA3
5 tritanopia 10.2 TMEM126A OPA3
6 encephalopathy due to defective mitochondrial and peroxisomal fission 1 10.2 YARS2 DNM1L
7 hereditary optic neuropathy 10.2 MT-ND6 MT-ND4
8 spinocerebellar ataxia, autosomal recessive 14 10.2 SPG7 AFG3L2
9 spastic ataxia 10.1 SPG7 DNM1L AFG3L2
10 mitochondrial dna-associated leigh syndrome 10.1 MT-ND6 MT-ND4
11 mitochondrial dna-associated leigh syndrome and narp 10.1 MT-ND6 MT-ND4
12 drug-induced hearing loss 10.1 MT-ND6 MT-ND4
13 wolfram syndrome 10.1 WFS1 TMEM126A OPA3
14 optic atrophy 9 10.1 SPG7 OPA3 AFG3L2
15 autosomal recessive isolated optic atrophy 10.1 YME1L1 TMEM126A
16 leber optic atrophy and dystonia 10.1 MT-ND6 MT-ND4
17 pearson marrow-pancreas syndrome 10.0 YARS2 MT-ND6 MT-ND4
18 neuropathy, ataxia, and retinitis pigmentosa 10.0 MT-ND6 MT-ND4
19 wolfram syndrome 2 10.0 WFS1 TMEM126A
20 carrion's disease 10.0 YME1L1 MT-ND4
21 charcot-marie-tooth disease intermediate type 9.9 YARS2 MFN2
22 mitochondrial encephalomyopathy 9.9 OPA1 MT-ND6 MT-ND4
23 lactic acidosis 9.9 YARS2 MT-ND6 MT-ND4 DNM1L
24 charcot-marie-tooth disease, axonal, type 2d 9.9 YARS2 MFN2
25 skin amelanotic melanoma 9.8 OPA1 MFN2 DNM1L
26 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.8 YARS2 MT-ND6 MT-ND4
27 early myoclonic encephalopathy 9.8 SPG7 MT-ND6 MT-ND4 AFG3L2
28 deafness, aminoglycoside-induced 9.8 MT-ND6 MT-ND4
29 perrault syndrome 9.8 YME1L1 YARS2 SPG7 AFG3L2
30 spastic paraplegia 7, autosomal recessive 9.7 YME1L1 SPG7 OPA1 AFG3L2
31 optic atrophy 11 9.7 YME1L1 MFN2
32 optic atrophy 7 with or without auditory neuropathy 9.7 WFS1 TMEM126A OPA3 MT-ND6 MT-ND4
33 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 9.7 OPA1 MFN2 DNM1L AFG3L2
34 mitochondrial disorders 9.7 YARS2 SPG7 OPA1 MT-ND6 MT-ND4
35 optic atrophy 3, autosomal dominant 9.7 TMEM126A SPG7 OPA3 MFN2
36 neuropathy, hereditary motor and sensory, type via, with optic atrophy 9.7 TMEM126A SPG7 OPA3 MFN2
37 spastic ataxia 5 9.7 YME1L1 SPG7 OMA1 AFG3L2
38 leber plus disease 9.7 WFS1 OPA3 MT-ND6 MT-ND4
39 spinocerebellar ataxia 28 9.7 YME1L1 SPG7 OMA1 AFG3L2
40 scotoma 9.6 TMEM126A OPA3 OPA1 MT-ND6 MT-ND4 DNM1L
41 optic atrophy 8 9.6 YME1L1 WFS1 TMEM126A OPA3 OMA1
42 behr syndrome 9.5 TMEM126A SPG7 OPA3 OPA1 MFN2
43 toxic optic neuropathy 9.5 TMEM126A OPA3 MT-ND6 MT-ND4 MFN2
44 mitochondrial myopathy 9.3 YARS2 SPG7 MT-ND6 MT-ND4 MFN2 DNM1L
45 chronic progressive external ophthalmoplegia 9.2 SPG7 OPA3 MT-ND6 MT-ND4 MFN2 AFG3L2
46 kearns-sayre syndrome 9.2 SPG7 OPA3 MT-ND6 MT-ND4 MFN2 AFG3L2
47 optic atrophy 4 9.0 YME1L1 WFS1 TMEM126A OPA3 OPA1 OMA1
48 optic atrophy 1 9.0 YME1L1 YARS2 SPG7 OPA1 OMA1 MFN2
49 peripheral nervous system disease 8.9 WFS1 SPG7 OPA3 OPA1 MT-ND6 MT-ND4
50 leber hereditary optic neuropathy, modifier of 8.9 WFS1 TMEM126A SPG7 OPA3 OPA1 MT-ND6

Graphical network of the top 20 diseases related to Optic Atrophy 5:



Diseases related to Optic Atrophy 5

Symptoms & Phenotypes for Optic Atrophy 5

Human phenotypes related to Optic Atrophy 5:

31
# Description HPO Frequency HPO Source Accession
1 optic atrophy 31 HP:0000648
2 central scotoma 31 HP:0000603
3 slow decrease in visual acuity 31 HP:0007924
4 tritanomaly 31 HP:0000552

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
central scotoma
slow decrease in visual acuity
optic nerve atrophy
dyschromatopsia, blue-yellow

Clinical features from OMIM®:

610708 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Optic Atrophy 5:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.81 AFG3L2 BCAS3 DNM1L MFN2 MT-ND6 OMA1
2 growth/size/body region MP:0005378 9.7 AFG3L2 BCAS3 DNM1L MFN2 MT-ND6 OMA1
3 muscle MP:0005369 9.17 AFG3L2 DNM1L MFN2 MT-ND6 OPA1 OPA3

Drugs & Therapeutics for Optic Atrophy 5

Search Clinical Trials , NIH Clinical Center for Optic Atrophy 5

Genetic Tests for Optic Atrophy 5

Genetic tests related to Optic Atrophy 5:

# Genetic test Affiliating Genes
1 Optic Atrophy 5 29 DNM1L

Anatomical Context for Optic Atrophy 5

MalaCards organs/tissues related to Optic Atrophy 5:

40
Eye, Retina, Pancreas, Skin

Publications for Optic Atrophy 5

Articles related to Optic Atrophy 5:

(show all 13)
# Title Authors PMID Year
1
Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission. 57 6 61
28969390 2017
2
A third locus for dominant optic atrophy on chromosome 22q. 57 6
15635063 2005
3
A novel de novo dominant negative mutation in DNM1L impairs mitochondrial fission and presents as childhood epileptic encephalopathy. 6
27145208 2016
4
Identification of copy number variation in the gene for autosomal dominant optic atrophy, OPA1, in a Chinese pedigree. 61
26400325 2015
5
First cases of dominant optic atrophy in Saudi Arabia: report of two novel OPA1 mutations. 61
24051421 2013
6
Dominant optic atrophy. 61
22776096 2012
7
Colonization and vertical transmission of Streptococcus mutans in Turkish children. 61
16735109 2008
8
Characterization of optical coherence topography findings in Kenny-Caffey syndrome. 61
17360206 2007
9
[Genetic basis of hereditary optic atrophies]. 61
18488399 2007
10
Structural model of the OPA1 GTPase domain may explain the molecular consequences of a novel mutation in a family with autosomal dominant optic atrophy. 61
16698014 2006
11
Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. 61
16648378 2006
12
Visual results, prognostic indicators, and posterior segment findings following surgery for cataract/lens subluxation-dislocation secondary to ocular contusion injuries. 61
12441722 2002
13
Vitiliginous chorioretinitis. 61
7295126 1981

Variations for Optic Atrophy 5

ClinVar genetic disease variations for Optic Atrophy 5:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DNM1L NM_012062.5(DNM1L):c.5A>C (p.Glu2Ala) SNV Pathogenic 446169 rs1555229948 GRCh37: 12:32832302-32832302
GRCh38: 12:32679368-32679368
2 DNM1L NM_012062.5(DNM1L):c.575C>A (p.Ala192Glu) SNV Pathogenic 446170 rs1555119216 GRCh37: 12:32866261-32866261
GRCh38: 12:32713327-32713327
3 DNM1L NM_012062.5(DNM1L):c.763_764dup (p.Lys256fs) Duplication Pathogenic 689730 rs1592631789 GRCh37: 12:32873619-32873620
GRCh38: 12:32720685-32720686
4 DNM1L , YARS2 NM_012062.5(DNM1L):c.1207C>T (p.Arg403Cys) SNV Pathogenic 214313 rs863223953 GRCh37: 12:32884296-32884296
GRCh38: 12:32731362-32731362
5 DNM1L , YARS2 NM_012062.5(DNM1L):c.2072A>G (p.Tyr691Cys) SNV Likely pathogenic 619028 rs1565548029 GRCh37: 12:32895600-32895600
GRCh38: 12:32742666-32742666
6 DNM1L NM_012062.5(DNM1L):c.305C>T (p.Thr102Met) SNV Uncertain significance 214308 rs201929226 GRCh37: 12:32861094-32861094
GRCh38: 12:32708160-32708160

UniProtKB/Swiss-Prot genetic disease variations for Optic Atrophy 5:

72
# Symbol AA change Variation ID SNP ID
1 DNM1L p.Glu2Ala VAR_080869 rs155522994
2 DNM1L p.Ala192Glu VAR_080871 rs155511921

Expression for Optic Atrophy 5

Search GEO for disease gene expression data for Optic Atrophy 5.

Pathways for Optic Atrophy 5

Pathways related to Optic Atrophy 5 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.41 WFS1 OPA1 OMA1 MFN2
2 11.29 OPA1 OMA1 AFG3L2

GO Terms for Optic Atrophy 5

Cellular components related to Optic Atrophy 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.56 YME1L1 TMEM126A SPG7 OPA1 OMA1 MT-ND6
2 mitochondrial membrane GO:0031966 9.55 OPA1 OMA1 MT-ND6 MT-ND4 DNM1L
3 mitochondrial outer membrane GO:0005741 9.5 OPA1 MFN2 DNM1L
4 mitochondrion GO:0005739 9.4 YME1L1 YARS2 TMEM126A SPG7 OPA3 OPA1
5 m-AAA complex GO:0005745 9.26 SPG7 AFG3L2

Biological processes related to Optic Atrophy 5 according to GeneCards Suite gene sharing:

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 protein-containing complex assembly GO:0065003 9.71 SPG7 DNM1L AFG3L2
2 response to nicotine GO:0035094 9.59 MT-ND6 MT-ND4
3 cristae formation GO:0042407 9.58 SPG7 AFG3L2
4 protein autoprocessing GO:0016540 9.58 OMA1 AFG3L2
5 mitochondrion morphogenesis GO:0070584 9.57 OPA1 DNM1L
6 positive regulation of dendritic spine morphogenesis GO:0061003 9.56 OPA1 DNM1L
7 protein complex oligomerization GO:0051259 9.55 OPA1 DNM1L
8 mitochondrion organization GO:0007005 9.55 YME1L1 SPG7 OPA1 DNM1L AFG3L2
9 mitochondrial respiratory chain complex I assembly GO:0032981 9.54 TMEM126A MT-ND6 MT-ND4
10 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.52 WFS1 OPA1
11 mitochondrial fission GO:0000266 9.51 OPA1 DNM1L
12 protein quality control for misfolded or incompletely synthesized proteins GO:0006515 9.49 YME1L1 OMA1
13 calcium import into the mitochondrion GO:0036444 9.48 OPA1 AFG3L2
14 intracellular distribution of mitochondria GO:0048312 9.46 OPA1 DNM1L
15 negative regulation of mitochondrial fusion GO:0010637 9.43 OMA1 DNM1L
16 mitochondrial calcium ion transmembrane transport GO:0006851 9.43 YME1L1 SPG7 AFG3L2
17 dynamin family protein polymerization involved in mitochondrial fission GO:0003374 9.4 OPA1 DNM1L
18 organelle fission GO:0048285 9.32 OPA1 DNM1L
19 mitochondrial fusion GO:0008053 9.26 SPG7 OPA1 MFN2 AFG3L2
20 mitochondrial protein processing GO:0034982 8.92 YME1L1 SPG7 OMA1 AFG3L2

Molecular functions related to Optic Atrophy 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.87 YME1L1 YARS2 SPG7 OPA1 MFN2 DNM1L
2 hydrolase activity GO:0016787 9.76 YME1L1 SPG7 OPA1 OMA1 MFN2 DNM1L
3 metallopeptidase activity GO:0008237 9.56 YME1L1 SPG7 OMA1 AFG3L2
4 metalloendopeptidase activity GO:0004222 9.26 YME1L1 SPG7 OMA1 AFG3L2
5 ATP-dependent peptidase activity GO:0004176 8.8 YME1L1 SPG7 AFG3L2

Sources for Optic Atrophy 5

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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