OPA3

outer mitochondrial membrane lipid metabolism regulator OPA3

Basic information

Region (hg38): 19:45527767-45602212

Links

ENSG00000125741 ∙ NCBI:80207 ∙ OMIM:606580 ∙ HGNC:8142 ∙ Uniprot:Q9H6K4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-methylglutaconic aciduria type 3 (Definitive), mode of inheritance: AR
• optic atrophy 3 (Supportive), mode of inheritance: AD
• 3-methylglutaconic aciduria type 3 (Supportive), mode of inheritance: AR
• 3-methylglutaconic aciduria type 3 (Strong), mode of inheritance: AR
• optic atrophy 3 (Strong), mode of inheritance: AD
• 3-methylglutaconic aciduria type 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3-methylglutaconic aciduria, type III; Optic atrophy 3, autosomal dominant	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	2494568; 7510656; 11668429; 12126933; 15342707; 22776096; 23700088; 24749080; 26190011

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OPA3 gene.

• 3-Methylglutaconic aciduria type 3;Optic atrophy 3 (4 variants)
• 3-Methylglutaconic aciduria type 3 (2 variants)
• not provided (2 variants)
• Optic atrophy 3;3-Methylglutaconic aciduria type 3 (1 variants)
• Optic atrophy 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OPA3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				119	1	120
missense	1	2	112	2		117
nonsense	1	6	13			20
start loss		1				1
frameshift		7	13			20
inframe indel			8			8
splice donor/acceptor (+/-2bp)	3	1				4
splice region			4	6	1	11
non coding			122	45	34	201
Total	5	17	268	166	35

Variants in OPA3

This is a list of pathogenic ClinVar variants found in the OPA3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-45528866-T-C			Benign (Jun 16, 2018)
19-45529054-T-A			Likely benign (Mar 16, 2021)
19-45529055-CCT-C		3-Methylglutaconic aciduria type 3	Uncertain significance (Oct 25, 2017)
19-45529057-T-C		3-Methylglutaconic aciduria type 3	Uncertain significance (Mar 13, 2018)
19-45529058-A-G		3-Methylglutaconic aciduria type 3	Uncertain significance (Aug 15, 2017)
19-45529064-C-TT		3-Methylglutaconic aciduria type 3 • 3-Methylglutaconic aciduria type 3;Optic atrophy 3	Uncertain significance (Jan 31, 2022)
19-45529065-G-A		3-Methylglutaconic aciduria type 3;Optic atrophy 3	Likely benign (Aug 21, 2018)
19-45529085-G-A		Inborn genetic diseases	Uncertain significance (Jul 01, 2024)
19-45529113-G-A		3-Methylglutaconic aciduria type 3;Optic atrophy 3	Benign/Likely benign (Feb 05, 2022)
19-45529118-C-T		3-Methylglutaconic aciduria type 3;Optic atrophy 3	not provided (-)
19-45529131-C-CAGCT		3-Methylglutaconic aciduria type 3;Optic atrophy 3	Uncertain significance (Feb 17, 2022)
19-45529141-C-T		Inborn genetic diseases	Uncertain significance (May 10, 2022)
19-45529145-G-A			Conflicting classifications of pathogenicity (Mar 06, 2024)
19-45529150-TCCAGG-T		3-Methylglutaconic aciduria type 3	Uncertain significance (Mar 13, 2018)
19-45529151-C-A		3-Methylglutaconic aciduria type 3	Uncertain significance (Jan 10, 2017)
19-45529153-AG-A		3-Methylglutaconic aciduria type 3 • 3-Methylglutaconic aciduria type 3;Optic atrophy 3 • Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
19-45529163-G-A		3-Methylglutaconic aciduria type 3	Uncertain significance (Mar 29, 2018)
19-45529178-G-A		3-Methylglutaconic aciduria type 3	Uncertain significance (Nov 22, 2017)
19-45529183-T-A		3-Methylglutaconic aciduria type 3;Optic atrophy 3	Likely benign (Nov 10, 2018)
19-45529184-G-A		3-Methylglutaconic aciduria type 3	Uncertain significance (Aug 11, 2017)
19-45529185-C-T		3-Methylglutaconic aciduria type 3;Optic atrophy 3	Likely benign (Aug 12, 2021)
19-45529193-A-G		3-Methylglutaconic aciduria type 3;Optic atrophy 3	Likely benign (Sep 07, 2018)
19-45529214-A-G		OPA3-related disorder	Likely benign (Jan 10, 2020)
19-45529216-T-A		Inborn genetic diseases	Uncertain significance (Nov 02, 2021)
19-45529218-GC-G		3-Methylglutaconic aciduria type 3	Uncertain significance (Jul 24, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OPA3	protein_coding	protein_coding	ENST00000323060	2	74786

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.566	0.391	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0520	109	111	0.986	0.00000570	1144
Missense in Polyphen		43	35.898	1.1978		399
Synonymous	0.122	51	52.1	0.978	0.00000285	393
Loss of Function	1.48	0	2.54	0.00	1.21e-7	26

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play some role in mitochondrial processes.
• Disease: DISEASE: Optic atrophy 3 (OPA3) [MIM:165300]: 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. OPA3 is associated with cataract and a neurologic disorder characterized by extrapyramidal signs and ataxia. {ECO:0000269|PubMed:15342707}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.318
• rvis_EVS: 0.37
• rvis_percentile_EVS: 75.12

Haploinsufficiency Scores

• pHI: 0.139
• hipred: N
• hipred_score: 0.323
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.343

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Opa3
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: visual perception;regulation of lipid metabolic process;regulation of growth;response to stimulus;neuromuscular process;mitochondrion morphogenesis
• Cellular component: mitochondrion