Optic Atrophy

Gene: OPA3

Green List (high evidence)

OPA3 (OPA3, outer mitochondrial membrane lipid metabolism regulator)
EnsemblGeneIds (GRCh38): ENSG00000125741
EnsemblGeneIds (GRCh37): ENSG00000125741
OMIM: 606580, Gene2Phenotype
OPA3 is in 19 panels

1 review

Teresa Zhao (Victorian Clinical Genetics Services)

Green List (high evidence)

Mutations in OPA3 can impart distinct phenotypes carried through dominant or recessive inheritance patterns but with the common universal feature of optic atrophy, underscoring the critical and susceptible role of mitochondrial health in optic nerve function (PMID: 31928268).

Intra- and interfamilial variability in age of onset and presenting symptoms was observed (PMID: 25159689).

Loss of function is a known mechanism of disease in this gene and is associated with 3-methylglutaconic aciduria, type III (MIM#258501) (PMID: 31928268). The precise mechanism for missense is unknown, however it was suggested they could cause dominant Optic atrophy 3 with cataract (MIM#165300) through either dominant negative or gain of function mechanism (PMID: 31119193).

Two transcripts: transcript variant 2 (exon 1 plus exon 2 [NM_025136.3]) and transcript variant 1 (exon 1 plus exon 3 [NM_001017989.2]), where transcript 2 is the predominant one in most tissues.
Created: 27 Jan 2021, 12:21 a.m. | Last Modified: 27 Jan 2021, 12:21 a.m.
Panel Version: 0.117

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD

Publications

Mode of pathogenicity
Other

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR
  • Optic atrophy 3 with cataract (MIM#165300), AD
OMIM
606580
Clinvar variants
Variants in OPA3
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

28 Jan 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: opa3 has been classified as Green List (High Evidence).

28 Jan 2021, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: OPA3 were changed from to 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD

28 Jan 2021, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: OPA3 were set to

28 Jan 2021, Gel status: 3

Set mode of pathogenicity

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of pathogenicity for gene: OPA3 was changed from to Other

28 Jan 2021, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: OPA3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: OPA3 was added gene: OPA3 was added to Optic Atrophy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: OPA3 was set to Unknown