OPA1
MCID: OPT053
MIFTS: 63

Optic Atrophy 1 (OPA1)

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

Aliases & Classifications for Optic Atrophy 1

MalaCards integrated aliases for Optic Atrophy 1:

Name: Optic Atrophy 1 56 12 52 73 13 15
Optic Atrophy Type 1 24 52 25 58
Opa1 56 12 52 73
Optic Atrophy, Kjer Type 56 52 25
Optic Atrophy, Juvenile 56 52 25
Kjer-Type Optic Atrophy 56 52 73
Oak 56 52 73
Autosomal Dominant Optic Atrophy, Classic Form 52 58
Optic Atrophy, Autosomal Dominant 25 71
Optic Atrophy, Hereditary, Autosomal Dominant 25
Autosomal Dominant Optic Atrophy, Kjer Type 58
Autosomal Dominant Optic Atrophy Kjer Type 25
Autosomal Dominant Optic Atrophy 25
Optic Atrophy, Kjer Type; Oak 56
Kjer Type Optic Atrophy 25
Optic Atrophy Kjer Type 73
Dominant Optic Atrophy 25
Optic Atrophy Juvenile 73
Atrophy, Optic, Type 1 39
Kjer's Optic Atrophy 25
Kjer Optic Atrophy 58
Adoa 25
Doa 25

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant optic atrophy, classic form
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

56
Miscellaneous:
incomplete penetrance
insidious onset
phenotypic variability
bimodal onset in early childhood (median 5 years) and young adulthood (21 to 30 years)
prevalence ranges from 1 in 12,000 to 1 in 50,000
see also optic atrophy with deafness , an allelic disorder

Inheritance:
autosomal dominant


HPO:

31
optic atrophy 1:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance insidious onset


GeneReviews:

24
Penetrance The estimated penetrance of 98% in opa1 has been revised in the light of molecular genetic studies. penetrance varies from family to family and pathogenic variant to pathogenic variant. it has been reported as high as 100% (variant c.1065+1g>t, resulting in exon 12 skipping) [thiselton et al 2002] and as low as 43% (variant c.2708_2711delttag in exon 27) [toomes et al 2001]. in these two studies the clinical diagnosis was made on the basis of reduced visual acuity, abnormal color discrimination, fundus examination showing temporal pallor of the optic disc, and electrophysiology studies [toomes et al 2001, thiselton et al 2002].

Classifications:

Orphanet: 58  
Rare eye diseases
Inborn errors of metabolism


Summaries for Optic Atrophy 1

NIH Rare Diseases : 52 Optic atrophy 1 , also known as optic atrophy type 1 is a disease that affects the optic nerve . The optic nerve carries signals from the eye to the brain about what is seen. People with optic atrophy type 1 have an optic nerve that has lost some tissue (atrophy ). This atrophy causes the optic nerve not to work as well as it should, which affects the vision. Signs and symptoms of optic atrophy type 1 include vision loss , difficulty distinguishing colors, and an abnormally pale appearance (pallor) of the optic nerve. The vision loss typically begins at age 4-6 years-old. The disease can occur in people of any ethnicity but seems to be more common in people of Danish descent. Other symptoms of optic atrophy type 1 may include sensorineural hearing loss , difficulty coordinating movements (ataxia ) and muscle disease (myopathy ). When people have optic atrophy type 1 and signs and symptoms other than vision loss, it is known as autosomal dominant optic atrophy plus syndrome . Optic atrophy type 1 is caused by a genetic change (pathogenic variant or mutation ) in the OPA1 gene . The disease is inherited in an autosomal dominant manner. Optic atrophy type 1 may be suspected when a person has signs and symptoms of the disease on an exam done by an ophthalmologist . Genetic testing may be used to confirm the diagnosis. Treatment for optic atrophy type 1 may include vision and hearing aids when necessary.

MalaCards based summary : Optic Atrophy 1, also known as optic atrophy type 1, is related to optic atrophy 5 and optic atrophy 4. An important gene associated with Optic Atrophy 1 is OPA1 (OPA1 Mitochondrial Dynamin Like GTPase), and among its related pathways/superpathways are Parkinson disease and Glucose / Energy Metabolism. The drugs Insulin, Globin Zinc and insulin have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and retina, and related phenotypes are optic atrophy and sensorineural hearing impairment

Disease Ontology : 12 An optic atrophy characterized by early childhood onset of visual impairment, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density that has material basis in heterozygous mutation in OPA1 on chromosome 3q29.

Genetics Home Reference : 25 Optic atrophy type 1 is a condition that often causes slowly worsening vision, usually beginning in childhood. People with optic atrophy type 1 typically experience a narrowing of their field of vision (tunnel vision). Affected individuals gradually lose their sight as their field of vision becomes smaller. Both eyes are usually affected equally, but the severity of the vision loss varies widely, even among affected members of the same family, ranging from nearly normal vision to complete blindness. In addition to vision loss, people with optic atrophy type 1 frequently have problems with color vision (color vision deficiency) that make it difficult or impossible to distinguish between shades of blue and green. In the early stages of the condition, individuals with optic atrophy type 1 experience a progressive loss of certain cells within the retina, which is a specialized light-sensitive tissue that lines the back of the eye. The loss of these cells (known as retinal ganglion cells) is followed by the degeneration (atrophy) of the nerves that relay visual information from the eye to the brain (optic nerves), which results in further vision loss. Atrophy causes these nerves to have an abnormally pale appearance (pallor), which can be seen during an eye examination.

OMIM : 56 Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (Votruba et al., 1998). Some patients with mutations in the OPA1 gene may also develop extraocular neurologic features, such as deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia; see 125250. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010). Yu-Wai-Man et al. (2009) provided a detailed review of autosomal dominant optic atrophy and Leber hereditary optic neuropathy (LHON; 535000), with emphasis on the selective vulnerability of retinal ganglion cells to mitochondrial dysfunction in both disorders. (165500)

UniProtKB/Swiss-Prot : 73 Optic atrophy 1: A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates 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. OPA1 is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disk pallor, color vision deficits, and centrocecal scotoma of variable density.

Wikipedia : 74 Dynamin-like 120 kDa protein, mitochondrial is a protein that in humans is encoded by the OPA1 gene.... more...

GeneReviews: NBK1248

Related Diseases for Optic Atrophy 1

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

Diseases related to Optic Atrophy 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 188)
# Related Disease Score Top Affiliating Genes
1 optic atrophy 5 33.5 OPA1 DNM1L
2 optic atrophy 4 32.9 OPA1 OMA1
3 mitochondrial encephalomyopathy 32.8 TFAM OPA1 MFF CYCS
4 spastic paraplegia 7, autosomal recessive 32.8 YME1L1 PARL OPA1
5 mitochondrial myopathy 32.5 TFAM PPARGC1A MFN2 DNM1L CYCS BLOC1S1
6 skin amelanotic melanoma 32.4 OPA1 FIS1
7 optic atrophy 11 32.3 YME1L1 TOMM20
8 mitochondrial metabolism disease 32.3 TOMM20 TFAM PPARGC1A PINK1 OPA1 MFN2
9 mitochondrial dna maintenance defects 32.2 TFAM OPA1
10 autosomal dominant progressive external ophthalmoplegia 32.2 TFAM OPA1
11 peripheral nervous system disease 32.0 PPARGC1A PINK1 OPA1 MIEF2 MFN2 MFN1
12 charcot-marie-tooth disease 32.0 YME1L1 PINK1 OPA1 MIEF2 MIEF1 MFN2
13 optic atrophy 3, autosomal dominant 31.2 MFN2 MFN1
14 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 30.7 OPA1 MFN2 DNM1L CYCS
15 cranial nerve disease 30.4 YME1L1 TFAM PPARGC1A PINK1 PARL OPA1
16 behr syndrome 30.2 OPA1 MFN2
17 spinocerebellar ataxia 28 30.2 YME1L1 OMA1
18 parkinson disease, late-onset 29.8 TOMM20 TFAM PINK1 PARL MFN2 MFN1
19 leber optic atrophy 29.7 TFAM PPARGC1A PINK1 PARL OPA1 MFN2
20 3-methylglutaconic aciduria, type iii 29.5 YME1L1 PINK1 PARL OPA6 OPA1 OMA1
21 optic nerve disease 28.4 YME1L1 TOMM20 TFAM PPARGC1A PINK1 PARL
22 autosomal dominant optic atrophy and peripheral neuropathy 12.4
23 mitochondrial dna depletion syndrome 14 12.2
24 glaucoma, normal tension 11.7
25 open-angle glaucoma 11.6
26 sensorineural hearing loss 11.6
27 hypertrophic cardiomyopathy 11.6
28 scotoma 11.6
29 ptosis 11.5
30 mitochondrial disorders 11.5
31 optic atrophy 8 11.5
32 auditory neuropathy spectrum disorder 11.4
33 bosch-boonstra-schaaf optic atrophy syndrome 11.3
34 mitochondrial dna depletion syndrome 11.3
35 fundus dystrophy 11.3
36 inherited retinal disorder 11.3
37 cerebellar ataxia, early-onset, with retained tendon reflexes 11.2
38 wolfram-like syndrome, autosomal dominant 11.2
39 retinitis pigmentosa 11.0
40 cone-rod dystrophy 1 11.0
41 usher syndrome, type iic 11.0
42 usher syndrome type 2 11.0
43 muscular dystrophy, congenital, megaconial type 10.4 TOMM20 PINK1
44 spastic ataxia 5 10.4 YME1L1 PARL OMA1
45 kearns-sayre syndrome 10.4
46 branchiootic syndrome 1 10.4
47 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.3 MFN2 MFN1 DNM1L BLOC1S1
48 encephalopathy due to defective mitochondrial and peroxisomal fission 1 10.3 MIEF2 MIEF1 MFF FIS1 DNM1L
49 glaucoma, primary open angle 10.3
50 yemenite deaf-blind hypopigmentation syndrome 10.3

Graphical network of the top 20 diseases related to Optic Atrophy 1:



Diseases related to Optic Atrophy 1

Symptoms & Phenotypes for Optic Atrophy 1

Human phenotypes related to Optic Atrophy 1:

58 31 (show top 50) (show all 55)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 optic atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000648
2 sensorineural hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000407
3 ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000602
4 color vision defect 58 31 frequent (33%) Frequent (79-30%) HP:0000551
5 sensorimotor neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007141
6 temporal optic disc pallor 58 31 frequent (33%) Frequent (79-30%) HP:0012511
7 morning glory anomaly 58 31 frequent (33%) Frequent (79-30%) HP:0025514
8 moderately reduced visual acuity 58 31 frequent (33%) Frequent (79-30%) HP:0030515
9 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
10 gait disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0001288
11 ataxia 58 31 very rare (1%) Occasional (29-5%) HP:0001251
12 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
13 central scotoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0000603
14 cataract 58 31 very rare (1%) Very rare (<4-1%) HP:0000518
15 global developmental delay 58 31 very rare (1%) Very rare (<4-1%) HP:0001263
16 hallucinations 58 31 very rare (1%) Very rare (<4-1%) HP:0000738
17 hypothyroidism 58 31 very rare (1%) Very rare (<4-1%) HP:0000821
18 fatigue 58 31 very rare (1%) Very rare (<4-1%) HP:0012378
19 dysphagia 58 31 very rare (1%) Very rare (<4-1%) HP:0002015
20 feeding difficulties 58 31 very rare (1%) Very rare (<4-1%) HP:0011968
21 skeletal muscle atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0003202
22 nystagmus 58 31 very rare (1%) Very rare (<4-1%) HP:0000639
23 myalgia 58 31 very rare (1%) Very rare (<4-1%) HP:0003326
24 scapular winging 58 31 very rare (1%) Very rare (<4-1%) HP:0003691
25 diabetes mellitus 58 31 very rare (1%) Very rare (<4-1%) HP:0000819
26 areflexia 58 31 very rare (1%) Very rare (<4-1%) HP:0001284
27 pes cavus 58 31 very rare (1%) Very rare (<4-1%) HP:0001761
28 migraine 58 31 very rare (1%) Very rare (<4-1%) HP:0002076
29 spastic paraplegia 58 31 very rare (1%) Very rare (<4-1%) HP:0001258
30 cerebellar atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0001272
31 hypogonadism 58 31 very rare (1%) Very rare (<4-1%) HP:0000135
32 hemiparesis 58 31 very rare (1%) Very rare (<4-1%) HP:0001269
33 dementia 58 31 very rare (1%) Very rare (<4-1%) HP:0000726
34 abnormality of the periventricular white matter 58 31 very rare (1%) Very rare (<4-1%) HP:0002518
35 macrocytic anemia 58 31 very rare (1%) Very rare (<4-1%) HP:0001972
36 atrophy/degeneration affecting the brainstem 58 31 very rare (1%) Very rare (<4-1%) HP:0007366
37 duane anomaly 58 31 very rare (1%) Very rare (<4-1%) HP:0009921
38 corpus callosum atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0007371
39 basal ganglia calcification 58 31 very rare (1%) Very rare (<4-1%) HP:0002135
40 weakness of facial musculature 58 31 very rare (1%) Very rare (<4-1%) HP:0030319
41 strabismus 31 very rare (1%) HP:0000486
42 progressive external ophthalmoplegia 31 very rare (1%) HP:0000590
43 proximal muscle weakness 31 very rare (1%) HP:0003701
44 horizontal nystagmus 31 very rare (1%) HP:0000666
45 seizure 31 very rare (1%) HP:0001250
46 seizures 58 Very rare (<4-1%)
47 visual impairment 58 Very frequent (99-80%)
48 cognitive impairment 58 Very rare (<4-1%)
49 spasticity 58 Very rare (<4-1%)
50 pallor 31 HP:0000980

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
optic atrophy
central scotoma
centrocecal scotoma
red-green dyschromatopsia
decreased visual acuity
more

Clinical features from OMIM:

165500

MGI Mouse Phenotypes related to Optic Atrophy 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.18 CYCS DNM1L MARCHF5 MFN1 MFN2 OMA1
2 cellular MP:0005384 10.13 BLOC1S1 CYCS DNM1L MARCHF5 MFN1 MFN2
3 cardiovascular system MP:0005385 10.07 CYCS DNM1L MFN2 OMA1 OPA1 PARL
4 growth/size/body region MP:0005378 10.03 CYCS DNM1L MARCHF5 MFN1 MFN2 OMA1
5 homeostasis/metabolism MP:0005376 9.93 BLOC1S1 DENR DNM1L FIS1 MARCHF5 MFN2
6 mortality/aging MP:0010768 9.83 BLOC1S1 CYCS DENR DNM1L FIS1 MARCHF5
7 muscle MP:0005369 9.17 DNM1L MFN2 OPA1 PARL PPARGC1A TFAM

Drugs & Therapeutics for Optic Atrophy 1

Drugs for Optic Atrophy 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Insulin, Globin Zinc
2 insulin

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Cross Sectional Study of Autosomal Dominant Opticus Atrophy Unknown status NCT01522638
2 Expression of Optic Atrophy Type 1 (OPA1) Protein in Lung Adenocarcinoma Unknown status NCT01249053
3 Transcorneal Electrical Stimulation Therapy for Retinal Disease - A Randomized, Single-blind Pilot Study Completed NCT00804102
4 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
5 Bone Marrow Derived Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541
6 Metabolic and Molecular Abnormalities in Response to Insulin and Exercise in Obesity and Type 2 Diabetes Active, not recruiting NCT03500016
7 Study of Neurological Pathological Mechanisms of and Neurodegenerative Diseases in Neurons and Glia Derived From Induced Stem Cells (iPS) in Patients and Healthy Family Controls. Not yet recruiting NCT03682458

Search NIH Clinical Center for Optic Atrophy 1

Genetic Tests for Optic Atrophy 1

Anatomical Context for Optic Atrophy 1

MalaCards organs/tissues related to Optic Atrophy 1:

40
Brain, Eye, Retina, Skeletal Muscle, Testes, Heart, Liver

Publications for Optic Atrophy 1

Articles related to Optic Atrophy 1:

(show top 50) (show all 1234)
# Title Authors PMID Year
1
Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. 61 56 6
11017079 2000
2
OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. 6 56 61
11017080 2000
3
Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method: a study of 38 British Isles pedigrees. 6 56 61
9490303 1998
4
OPA1 R445H mutation in optic atrophy associated with sensorineural deafness. 24 56 61
16240368 2005
5
Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1. 24 61 56
15531309 2004
6
Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy. 61 24 56
15505825 2004
7
Spectrum, frequency and penetrance of OPA1 mutations in dominant optic atrophy. 61 6 24
11440989 2001
8
Dominant optic atrophy. Refining the clinical diagnostic criteria in light of genetic linkage studies. 56 6
9917792 1999
9
A third locus for dominant optic atrophy on chromosome 22q. 24 6
15635063 2005
10
Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission. 61 6
28969390 2017
11
Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. 6 61
25012220 2014
12
Retinal nerve fiber layer thickness in dominant optic atrophy measurements by optical coherence tomography and correlation with age. 56 61
21621262 2011
13
Early-onset severe neuromuscular phenotype associated with compound heterozygosity for OPA1 mutations. 6 61
21636302 2011
14
Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations. 61 56
20837821 2011
15
OPA1 mutations associated with dominant optic atrophy influence optic nerve head size. 61 56
20417568 2010
16
The prevalence and natural history of dominant optic atrophy due to OPA1 mutations. 61 56
20417570 2010
17
OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules. 56 61
20484224 2010
18
OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. 61 56
20185555 2010
19
Multi-system neurological disease is common in patients with OPA1 mutations. 61 56
20157015 2010
20
Inherited mitochondrial optic neuropathies. 61 56
19001017 2009
21
Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy. 56 61
19181907 2009
22
Hereditary optic neuropathies share a common mitochondrial coupling defect. 61 56
18496845 2008
23
Comprehensive cDNA study and quantitative transcript analysis of mutant OPA1 transcripts containing premature termination codons. 6 61
17722006 2008
24
Optic Atrophy Type 1 61 6
20301426 2007
25
Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. 61 56
17428816 2007
26
Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. 61 56
17306754 2007
27
A novel OPA1 mutation responsible for autosomal dominant optic atrophy with high frequency hearing loss in a Chinese family. 61 6
17188070 2007
28
Mitochondrial DNA content is decreased in autosomal dominant optic atrophy. 61 56
15781809 2005
29
A frameshift mutation in exon 28 of the OPA1 gene explains the high prevalence of dominant optic atrophy in the Danish population: evidence for a founder effect. 6 61
11735024 2001
30
Dominant optic atrophy: exclusion and fine genetic mapping of the candidate gene, HRY. 61 56
9745030 1998
31
Linkage studies in dominant optic atrophy, Kjer type: possible evidence for heterogeneity. 56 61
9429135 1997
32
Genetic refinement of dominant optic atrophy (OPA1) locus to within a 2 cM interval of chromosome 3q. 61 56
9039986 1997
33
Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1) 56 61
9006432 1997
34
Dominant optic atrophy, Kjer type. Linkage analysis and clinical features in a large British pedigree. 61 56
9006433 1997
35
No evidence of genetic heterogeneity in dominant optic atrophy. 61 56
8825922 1995
36
Refinement of the OPA1 gene locus on chromosome 3q28-q29 to a region of 2-8 cM, in one Cuban pedigree with autosomal dominant optic atrophy type Kjer. 61 56
7573062 1995
37
Dominant optic atrophy (OPA1) mapped to chromosome 3q region. I. Linkage analysis. 61 56
7951248 1994
38
Sensorineural hearing loss in OPA1-linked disorders. 24 61
23384603 2013
39
Idebenone treatment in patients with OPA1-mutant dominant optic atrophy. 61 52
23388408 2013
40
Alu-element insertion in an OPA1 intron sequence associated with autosomal dominant optic atrophy. 24 61
20157369 2010
41
Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations. 61 24
19319978 2009
42
Reversible optic neuropathy with OPA1 exon 5b mutation. 61 24
18360822 2008
43
OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes. 24 61
18158317 2008
44
Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. 24 61
18065439 2008
45
Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1. 24 61
18195150 2008
46
Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. 24 61
16648378 2006
47
Novel mutations in the OPA1 gene and associated clinical features in Japanese patients with optic atrophy. 61 24
16513463 2006
48
Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. 24 61
16437557 2006
49
Expression of the Opa1 mitochondrial protein in retinal ganglion cells: its downregulation causes aggregation of the mitochondrial network. 24 61
16249510 2005
50
Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation. 61 24
16158427 2005

Variations for Optic Atrophy 1

ClinVar genetic disease variations for Optic Atrophy 1:

6 (show top 50) (show all 137) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 OPA1 NM_015560.2(OPA1):c.1346C>G (p.Thr449Arg)SNV Pathogenic 802041 3:193361797-193361797 3:193644008-193644008
2 OPA1 NM_015560.2(OPA1):c.2150_2151del (p.Phe717fs)deletion Pathogenic 802042 3:193375004-193375005 3:193657215-193657216
3 OPA1 NM_015560.2(OPA1):c.899G>A (p.Gly300Glu)SNV Pathogenic 5080 rs28939082 3:193355769-193355769 3:193637980-193637980
4 OPA1 NM_015560.2(OPA1):c.985-1G>ASNV Pathogenic 5081 rs879255510 3:193360553-193360553 3:193642764-193642764
5 OPA1 NM_015560.2(OPA1):c.2708_2711delTTAGdeletion Pathogenic 5082 rs80356530 3:193384957-193384960 3:193667168-193667171
6 OPA1 NM_130831.3(OPA1):c.2717_2720del (p.Val906fs)deletion Pathogenic 5083 rs879255560 3:193409856-193409859 3:193692067-193692070
7 OPA1 NM_015560.2(OPA1):c.869G>A (p.Arg290Gln)SNV Pathogenic 5084 rs121908375 3:193355069-193355069 3:193637280-193637280
8 OPA1 NM_015560.2(OPA1):c.1096C>T (p.Arg366Ter)SNV Pathogenic 5085 rs104893753 3:193360794-193360794 3:193643005-193643005
9 OPA1 NM_130831.3(OPA1):c.1185_1187CAT[1] (p.Ile397del)short repeat Pathogenic 5086 rs879255511 3:193361397-193361399 3:193643608-193643610
10 OPA1 NM_015560.2(OPA1):c.1354del (p.Val452fs)deletion Pathogenic 5087 rs879255512 3:193361804-193361804 3:193644015-193644015
11 OPA1 NM_015560.2(OPA1):c.2826del (p.Arg943fs)deletion Pathogenic 5088 rs80356531 3:193409858-193409858 3:193692069-193692069
12 OPA1 NM_015560.2(OPA1):c.2848_2849del (p.Asp950fs)deletion Pathogenic 5092 rs879255513 3:193409881-193409882 3:193692092-193692093
13 OPA1 NM_015560.2(OPA1):c.1065+1G>TSNV Pathogenic 21527 rs80356528 3:193360635-193360635 3:193642846-193642846
14 OPA1 NM_015560.2(OPA1):c.983A>G (p.Lys328Arg)SNV Pathogenic 95733 rs398124303 3:193355853-193355853 3:193638064-193638064
15 OPA1 NM_015560.2(OPA1):c.728T>A (p.Leu243Ter)SNV Pathogenic 217840 rs863225274 3:193353256-193353256 3:193635467-193635467
16 OPA1 NM_015560.2(OPA1):c.1067_1068dup (p.Ala357fs)duplication Pathogenic 217841 rs863225275 3:193360764-193360765 3:193642975-193642976
17 OPA1 NM_015560.2(OPA1):c.1202G>A (p.Gly401Asp)SNV Pathogenic 217842 rs863225276 3:193361223-193361223 3:193643434-193643434
18 OPA1 NM_015560.2(OPA1):c.1310A>G (p.Gln437Arg)SNV Pathogenic 217843 rs863225277 3:193361414-193361414 3:193643625-193643625
19 OPA1 NM_015560.2(OPA1):c.2131C>T (p.Arg711Ter)SNV Pathogenic/Likely pathogenic 216979 rs863224906 3:193374986-193374986 3:193657197-193657197
20 OPA1 NM_015560.2(OPA1):c.870+5G>ASNV Pathogenic/Likely pathogenic 431939 rs754576717 3:193355075-193355075 3:193637286-193637286
21 OPA1 NM_015560.2(OPA1):c.871G>C (p.Val291Leu)SNV Likely pathogenic 451258 rs1553876590 3:193355741-193355741 3:193637952-193637952
22 OPA1 NM_015560.2(OPA1):c.2818+6T>ASNV Likely pathogenic 802043 3:193385075-193385075 3:193667286-193667286
23 OPA1 NM_015560.2(OPA1):c.886G>C (p.Asp296His)SNV Likely pathogenic 802038 3:193355756-193355756 3:193637967-193637967
24 OPA1 NM_015560.2(OPA1):c.1289A>T (p.Asn430Ile)SNV Likely pathogenic 802040 3:193361393-193361393 3:193643604-193643604
25 OPA1 NM_015560.2(OPA1):c.2341C>T (p.Arg781Trp)SNV Conflicting interpretations of pathogenicity 214911 rs190235251 3:193377336-193377336 3:193659547-193659547
26 OPA1 NM_015560.2(OPA1):c.599C>T (p.Ser200Phe)SNV Conflicting interpretations of pathogenicity 344482 rs200243596 3:193336700-193336700 3:193618911-193618911
27 OPA1 NM_015560.2(OPA1):c.-10C>TSNV Conflicting interpretations of pathogenicity 378310 rs775614028 3:193311157-193311157 3:193593368-193593368
28 OPA1 NM_015560.2(OPA1):c.2808G>C (p.Ala936=)SNV Conflicting interpretations of pathogenicity 388730 rs117475774 3:193385059-193385059 3:193667270-193667270
29 OPA1 NM_015560.2(OPA1):c.2427T>C (p.Leu809=)SNV Conflicting interpretations of pathogenicity 382460 rs145999595 3:193380682-193380682 3:193662893-193662893
30 OPA1 NM_015560.2(OPA1):c.2797G>A (p.Val933Ile)SNV Conflicting interpretations of pathogenicity 427152 rs375733283 3:193385048-193385048 3:193667259-193667259
31 OPA1 NM_015560.2(OPA1):c.239A>G (p.Tyr80Cys)SNV Conflicting interpretations of pathogenicity 596133 rs151103940 3:193332718-193332718 3:193614929-193614929
32 OPA1 NM_015560.2(OPA1):c.1923G>A (p.Ala641=)SNV Conflicting interpretations of pathogenicity 195515 rs138114609 3:193372726-193372726 3:193654937-193654937
33 OPA1 NM_015560.2(OPA1):c.70A>G (p.Ile24Val)SNV Conflicting interpretations of pathogenicity 214887 rs201520438 3:193332549-193332549 3:193614760-193614760
34 OPA1 NM_015560.2(OPA1):c.88C>T (p.Leu30=)SNV Conflicting interpretations of pathogenicity 214888 rs185976555 3:193332567-193332567 3:193614778-193614778
35 OPA1 NM_015560.2(OPA1):c.530G>T (p.Ser177Ile)SNV Conflicting interpretations of pathogenicity 214897 rs150279202 3:193335048-193335048 3:193617259-193617259
36 OPA1 NM_015560.2(OPA1):c.1146A>G (p.Ile382Met)SNV Conflicting interpretations of pathogenicity 50866 rs143319805 3:193361167-193361167 3:193643378-193643378
37 OPA1 NM_015560.2(OPA1):c.625-5459G>ASNV Uncertain significance 65755 rs138350727 3:193343942-193343942 3:193626153-193626153
38 OPA1 NM_130831.3(OPA1):c.578A>G (p.Tyr193Cys)SNV Uncertain significance 902455 3:193353214-193353214 3:193635425-193635425
39 OPA1 NM_130831.3(OPA1):c.712G>A (p.Val238Ile)SNV Uncertain significance 902456 3:193355020-193355020 3:193637231-193637231
40 OPA1 NC_000003.12:g.193593196C>ASNV Uncertain significance 903246 3:193310985-193310985 3:193593196-193593196
41 OPA1 NM_015560.2(OPA1):c.1123T>G (p.Cys375Gly)SNV Uncertain significance 802039 3:193360821-193360821 3:193643032-193643032
42 OPA1 NM_130831.3(OPA1):c.-144T>CSNV Uncertain significance 903248 3:193311023-193311023 3:193593234-193593234
43 OPA1 NM_130831.3(OPA1):c.-3G>ASNV Uncertain significance 903249 3:193311164-193311164 3:193593375-193593375
44 OPA1 NM_130831.3(OPA1):c.1318G>A (p.Val440Ile)SNV Uncertain significance 903317 3:193361877-193361877 3:193644088-193644088
45 OPA1 NM_130831.3(OPA1):c.1566G>A (p.Glu522=)SNV Uncertain significance 899711 3:193364938-193364938 3:193647149-193647149
46 OPA1 NM_130831.3(OPA1):c.2258A>G (p.Asn753Ser)SNV Uncertain significance 899712 3:193380621-193380621 3:193662832-193662832
47 OPA1 NM_130831.3(OPA1):c.2743G>A (p.Ala915Thr)SNV Uncertain significance 902537 3:193409884-193409884 3:193692095-193692095
48 OPA1 NM_130831.3(OPA1):c.*341G>TSNV Uncertain significance 903387 3:193412730-193412730 3:193694941-193694941
49 OPA1 NM_130831.3(OPA1):c.*403T>CSNV Uncertain significance 903388 3:193412792-193412792 3:193695003-193695003
50 OPA1 NM_130831.3(OPA1):c.*427A>TSNV Uncertain significance 903389 3:193412816-193412816 3:193695027-193695027

UniProtKB/Swiss-Prot genetic disease variations for Optic Atrophy 1:

73 (show all 48)
# Symbol AA change Variation ID SNP ID
1 OPA1 p.Arg290Gln VAR_011483 rs121908375
2 OPA1 p.Gly300Glu VAR_011484 rs28939082
3 OPA1 p.Arg445His VAR_015741 rs80356529
4 OPA1 p.Leu396Arg VAR_022927 rs727504060
5 OPA1 p.Thr503Lys VAR_022928
6 OPA1 p.Arg571His VAR_022929 rs140606054
7 OPA1 p.Ser545Arg VAR_026533 rs398124298
8 OPA1 p.Leu939Pro VAR_028370
9 OPA1 p.Tyr80Cys VAR_060826 rs151103940
10 OPA1 p.Thr95Met VAR_060827 rs201214736
11 OPA1 p.Tyr102Cys VAR_060828 rs530896300
12 OPA1 p.Glu270Lys VAR_060829
13 OPA1 p.Leu272Pro VAR_060830
14 OPA1 p.Asp273Ala VAR_060831
15 OPA1 p.Arg290Trp VAR_060832 rs780333963
16 OPA1 p.Gln310Arg VAR_060834 rs770966290
17 OPA1 p.Ala357Thr VAR_060836 rs190223702
18 OPA1 p.Ile382Met VAR_060837 rs143319805
19 OPA1 p.Leu384Phe VAR_060838
20 OPA1 p.Leu396Pro VAR_060839 rs727504060
21 OPA1 p.Asn430Asp VAR_060841
22 OPA1 p.Asp438Val VAR_060842
23 OPA1 p.Thr449Arg VAR_060843
24 OPA1 p.Lys468Glu VAR_060845
25 OPA1 p.Asp470Gly VAR_060846
26 OPA1 p.Glu487Lys VAR_060847
27 OPA1 p.Lys505Asn VAR_060848
28 OPA1 p.Cys551Tyr VAR_060851 rs879255592
29 OPA1 p.Leu574Pro VAR_060852
30 OPA1 p.Arg590Gln VAR_060854 rs147077380
31 OPA1 p.Arg590Trp VAR_060855 rs778998909
32 OPA1 p.Leu593Pro VAR_060856
33 OPA1 p.Ser646Leu VAR_060857
34 OPA1 p.Asn728Lys VAR_060859 rs129285246
35 OPA1 p.Gly768Asp VAR_060860
36 OPA1 p.Arg781Trp VAR_060861 rs190235251
37 OPA1 p.Gln785Arg VAR_060862 rs106479730
38 OPA1 p.Ser823Tyr VAR_060863
39 OPA1 p.Tyr841Cys VAR_060864
40 OPA1 p.Arg882Leu VAR_060865
41 OPA1 p.Leu887Pro VAR_060866
42 OPA1 p.Arg932Cys VAR_060868 rs145710079
43 OPA1 p.Leu949Pro VAR_060869
44 OPA1 p.Pro400Ala VAR_067355
45 OPA1 p.Thr330Ser VAR_072125
46 OPA1 p.Val377Ile VAR_072126 rs780922750
47 OPA1 p.Gly439Val VAR_072127 rs387906900
48 OPA1 p.Gly459Glu VAR_072129

Expression for Optic Atrophy 1

Search GEO for disease gene expression data for Optic Atrophy 1.

Pathways for Optic Atrophy 1

GO Terms for Optic Atrophy 1

Cellular components related to Optic Atrophy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.33 YME1L1 TOMM20 PINK1 PARL OPA1 OMA1
2 integral component of membrane GO:0016021 10.25 YME1L1 TOMM20 PINK1 PARL OPA1 OMA1
3 mitochondrial inner membrane GO:0005743 9.85 YME1L1 PINK1 PARL OPA1 OMA1 CYCS
4 mitochondrial outer membrane GO:0005741 9.7 TOMM20 PINK1 OPA1 MIEF2 MIEF1 MFN2
5 peroxisome GO:0005777 9.65 MIEF2 MIEF1 MFF FIS1 DNM1L
6 mitochondrial intermembrane space GO:0005758 9.62 PINK1 OPA1 CYCS BLOC1S1
7 integral component of mitochondrial outer membrane GO:0031307 9.55 TOMM20 PINK1 MFN1 MFF FIS1
8 mitochondrion GO:0005739 9.55 YME1L1 TOMM20 TFAM PINK1 PARL OPA1
9 intrinsic component of mitochondrial outer membrane GO:0031306 9.4 MFN2 MFN1

Biological processes related to Optic Atrophy 1 according to GeneCards Suite gene sharing:

(show all 46)
# Name GO ID Score Top Affiliating Genes
1 cellular response to hypoxia GO:0071456 9.89 PPARGC1A PINK1 OPA1 MIEF1
2 cellular response to oxidative stress GO:0034599 9.85 PPARGC1A PINK1 CYCS
3 positive regulation of cold-induced thermogenesis GO:0120162 9.85 PPARGC1A OMA1 MFN2
4 macroautophagy GO:0016236 9.85 TOMM20 PINK1 MFN2 MFN1
5 response to nutrient levels GO:0031667 9.83 PPARGC1A OPA1 FIS1
6 cellular response to glucose stimulus GO:0071333 9.83 PPARGC1A OPA1 FIS1
7 autophagy of mitochondrion GO:0000422 9.77 PPARGC1A PINK1 FIS1
8 positive regulation of protein targeting to membrane GO:0090314 9.76 MIEF2 MIEF1 MFF FIS1
9 positive regulation of release of cytochrome c from mitochondria GO:0090200 9.75 PINK1 MFF DNM1L
10 protein targeting to mitochondrion GO:0006626 9.73 TOMM20 MFN2 MFF FIS1
11 regulation of mitochondrion organization GO:0010821 9.73 PINK1 PARL MIEF2 MFF FIS1 DNM1L
12 mitochondrial fission GO:0000266 9.72 OPA1 MIEF1 MFF FIS1 DNM1L
13 release of cytochrome c from mitochondria GO:0001836 9.71 MFF FIS1 DNM1L
14 mitochondrion morphogenesis GO:0070584 9.71 OPA1 MFF FIS1 DNM1L
15 regulation of reactive oxygen species metabolic process GO:2000377 9.7 PINK1 PARL
16 positive regulation of dendritic spine morphogenesis GO:0061003 9.7 OPA1 DNM1L
17 regulation of autophagy of mitochondrion GO:1903146 9.7 PINK1 PARL DNM1L
18 positive regulation of mitochondrial fission GO:0090141 9.7 PINK1 MIEF2 MIEF1 MFF MARCHF5 FIS1
19 mitochondrial calcium ion transmembrane transport GO:0006851 9.69 YME1L1 PARL
20 negative regulation of release of cytochrome c from mitochondria GO:0090201 9.69 PARL OPA1
21 respiratory electron transport chain GO:0022904 9.69 PPARGC1A PINK1
22 peroxisome fission GO:0016559 9.69 MFF FIS1 DNM1L
23 protein complex oligomerization GO:0051259 9.68 OPA1 DNM1L
24 cellular respiration GO:0045333 9.68 PPARGC1A CYCS
25 positive regulation of ATP biosynthetic process GO:2001171 9.67 PPARGC1A PINK1
26 GTP metabolic process GO:0046039 9.67 OPA1 MFN1
27 protein quality control for misfolded or incompletely synthesized proteins GO:0006515 9.67 YME1L1 OMA1
28 mitochondrial fragmentation involved in apoptotic process GO:0043653 9.67 MFF FIS1 DNM1L
29 response to muscle activity GO:0014850 9.67 TOMM20 PPARGC1A OPA1 FIS1
30 negative regulation of mitochondrial fusion GO:0010637 9.66 OMA1 DNM1L
31 cellular response to lipid GO:0071396 9.65 FIS1 DNM1L
32 mitochondrion localization GO:0051646 9.65 MFN2 MFN1
33 dynamin family protein polymerization involved in mitochondrial fission GO:0003374 9.65 OPA1 MIEF2 DNM1L
34 intracellular distribution of mitochondria GO:0048312 9.64 OPA1 DNM1L
35 regulation of protein targeting to mitochondrion GO:1903214 9.64 PINK1 PARL
36 cellular response to toxic substance GO:0097237 9.63 PINK1 FIS1
37 protein localization to mitochondrion GO:0070585 9.63 MARCHF5 DNM1L
38 organelle fission GO:0048285 9.62 OPA1 DNM1L
39 mitochondrial protein processing GO:0034982 9.62 YME1L1 OMA1
40 response to hypobaric hypoxia GO:1990910 9.61 FIS1 DNM1L
41 negative regulation of mitochondrial fission GO:0090258 9.61 PPARGC1A PINK1
42 regulation of peroxisome organization GO:1900063 9.58 MFF DNM1L
43 response to flavonoid GO:1905395 9.57 FIS1 DNM1L
44 cellular response to thapsigargin GO:1904579 9.56 FIS1 DNM1L
45 mitochondrial fusion GO:0008053 9.5 OPA1 MIEF2 MIEF1 MFN2 MFN1 MFF
46 mitochondrion organization GO:0007005 9.28 YME1L1 TFAM PPARGC1A PINK1 OPA1 OMA1

Molecular functions related to Optic Atrophy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.8 YME1L1 PARL OPA1 OMA1 MFN2 MFN1
2 GTP binding GO:0005525 9.62 OPA1 MFN2 MFN1 DNM1L
3 protein binding GO:0005515 9.58 YME1L1 TOMM20 TFAM PPARGC1A PINK1 PARL
4 GTPase activity GO:0003924 9.46 OPA1 MFN2 MFN1 DNM1L
5 ubiquitin protein ligase binding GO:0031625 9.26 PPARGC1A PINK1 MFN2 DNM1L

Sources for Optic Atrophy 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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