Details of Disease

Disease Name

Autosomal dominant optic atrophy, classic form

Kjer-type optic atrophy; optic atrophy, Kjer type; OAK; optic atrophy, juvenile; OPA1; optic atrophy 1; autosomal dominant optic atrophy, Kjer type; optic atrophy type 1; Kjer optic atrophy

Definition

One of the most common forms of hereditary optic neuropathy characterized by progressive bilateral visual loss during the first decade of life, associated with optic disk pallor, visual field and color vision defects.

Disease Hierarchy

DISOCR1N: Autosomal dominant optic atrophy

DISK7IP8: Mitochondrial oxidative phosphorylation disorder

DISXUAV9: Autosomal dominant optic atrophy, classic form

Disease Identifiers

MONDO ID

MONDO_0008134

MESH ID

D029241

UMLS CUI

C0338508

OMIM ID

165500

MedGen ID

137902

Orphanet ID

98673

SNOMED CT ID

717336005

General Information of Disease (ID: DISXUAV9)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SIRT3	TTVZLIJ	moderate	Biomarker	[1]
ACO2	TTMTF2P	Strong	Genetic Variation	[2]
PLIN1	TTIV27N	Strong	Biomarker	[3]
SLC14A1	TTWVJU1	Strong	Genetic Variation	[4]
SLC5A1	TT2UE56	Strong	Biomarker	[5]
UTRN	TTNO1VA	Strong	Posttranslational Modification	[6]
OPA1	TTTU49Q	Definitive	Autosomal dominant	[7]
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⏷ Show the Full List of 7 DTT(s)

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CRMP1	DE0EUXB	Strong	Posttranslational Modification	[6]
FXN	DEXVHDB	Strong	Genetic Variation	[8]
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This Disease Is Related to 42 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MFN1	OTCBXQZF	Limited	Biomarker	[9]
DNM1L	OTXK1Q1G	Supportive	Autosomal dominant	[10]
IMMT	OTBDSLE7	moderate	Biomarker	[11]
MCU	OTQZAYWQ	moderate	Altered Expression	[12]
ADCK1	OTB7NSK3	Strong	Biomarker	[11]
AKAP1	OTIIB2JB	Strong	Genetic Variation	[13]
ASAP2	OTGEXULW	Strong	Biomarker	[14]
BNIP3L	OTJKOMXE	Strong	Biomarker	[15]
CCDC50	OTSE1YM5	Strong	Genetic Variation	[16]
CTRL	OTB6NA5O	Strong	Biomarker	[14]
CYC1	OT0962IM	Strong	Genetic Variation	[9]
DAPK2	OTWODUQG	Strong	Posttranslational Modification	[6]
DENR	OTXP9HOY	Strong	Posttranslational Modification	[6]
DGKG	OTBL32T3	Strong	Genetic Variation	[17]
FIS1	OT2HL10J	Strong	Genetic Variation	[18]
GABARAPL1	OT4U7SBG	Strong	Biomarker	[15]
KIF1B	OTI1XQTO	Strong	Biomarker	[19]
MED12	OTQZ4D2X	Strong	Biomarker	[20]
MFF	OTEVIXOM	Strong	Biomarker	[21]
MRPS30	OTDXIAGG	Strong	Biomarker	[14]
MTPAP	OT6HQ02S	Strong	Biomarker	[14]
NDUFV2	OTSZF7D6	Strong	Genetic Variation	[9]
NFE2L1	OT1QHOS2	Strong	Altered Expression	[22]
NRF1	OTOXWNV8	Strong	Altered Expression	[22]
OMA1	OT0JRVY7	Strong	Biomarker	[23]
OPA3	OT6NDC1M	Strong	Biomarker	[24]
PACC1	OTKBS8CC	Strong	Genetic Variation	[25]
PAPOLA	OTPHD65D	Strong	Biomarker	[14]
PDAP1	OTJSWMOD	Strong	Biomarker	[14]
PGAM5	OT6Q5M0C	Strong	Altered Expression	[26]
PHLDA2	OTMV9DPP	Strong	Genetic Variation	[27]
SDHA	OTOJ8QFF	Strong	Genetic Variation	[9]
SSBP1	OTH2PZWH	Strong	Genetic Variation	[28]
TFB2M	OTG9DUU1	Strong	Biomarker	[22]
TMED9	OTYGAQS0	Strong	Altered Expression	[29]
TOMM40	OTZDQ29F	Strong	Genetic Variation	[30]
TOMM70	OT8QBYZ0	Strong	Biomarker	[31]
TPPP	OTCFMSUF	Strong	Altered Expression	[29]
TREH	OTJE0NOY	Strong	Altered Expression	[32]
APTX	OTPAS5G8	Definitive	Altered Expression	[33]
MAD2L1BP	OT2O2IUJ	Definitive	Biomarker	[19]
OPA1	OTJGNWPW	Definitive	Autosomal dominant	[7]
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⏷ Show the Full List of 42 DOT(s)

References

1	Sirt3 modulate renal ischemia-reperfusion injury through enhancing mitochondrial fusion and activating the ERK-OPA1 signaling pathway.J Cell Physiol. 2019 Dec;234(12):23495-23506. doi: 10.1002/jcp.28918. Epub 2019 Jun 7.
2	Derivation of a human DOA iPSC line, IISHDOi006-A, with a mutation in the ACO2 gene: c.1999G>A; p.Glu667Lys.Stem Cell Res. 2019 Oct;40:101566. doi: 10.1016/j.scr.2019.101566. Epub 2019 Aug 29.
3	OPA1-anchored PKA phosphorylates perilipin 1 on S522 and S497 in adipocytes differentiated from human adipose stem cells.Mol Biol Cell. 2018 Jun 15;29(12):1487-1501. doi: 10.1091/mbc.E17-09-0538. Epub 2018 Apr 24.
4	Genetic heterogeneity of dominant optic atrophy, Kjer type: Identification of a second locus on chromosome 18q12.2-12.3.Arch Ophthalmol. 1999 Jun;117(6):805-10. doi: 10.1001/archopht.117.6.805.
5	Leptin enhances glycolysis via OPA1-mediated mitochondrial fusion to promote mesenchymal stem cell survival.Int J Mol Med. 2019 Jul;44(1):301-312. doi: 10.3892/ijmm.2019.4189. Epub 2019 May 9.
6	Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins.Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):622-635. doi: 10.1161/ATVBAHA.117.310605. Epub 2018 Feb 1.
7	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
8	Mitochondria.J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1188-99. doi: 10.1136/jnnp.74.9.1188.
9	Fluoride-induced renal dysfunction via respiratory chain complex abnormal expression and fusion elevation in mice.Chemosphere. 2020 Jan;238:124607. doi: 10.1016/j.chemosphere.2019.124607. Epub 2019 Aug 17.
10	Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission. Brain. 2017 Oct 1;140(10):2586-2596. doi: 10.1093/brain/awx219.
11	Drosophila ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle.PLoS Genet. 2019 May 24;15(5):e1008184. doi: 10.1371/journal.pgen.1008184. eCollection 2019 May.
12	MCU Up-regulation contributes to myocardial ischemia-reperfusion Injury through calpain/OPA-1-mediated mitochondrial fusion/mitophagy Inhibition.J Cell Mol Med. 2019 Nov;23(11):7830-7843. doi: 10.1111/jcmm.14662. Epub 2019 Sep 9.
13	Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission.Circ Res. 2018 Jan 5;122(1):58-73. doi: 10.1161/CIRCRESAHA.117.311307. Epub 2017 Nov 1.
14	Facilitating physical activity and reducing symptoms in patients with knee osteoarthritis: study protocol of a randomized controlled trial to test a theory-based PrevOP-psychological adherence program (PrevOP-PAP).BMC Musculoskelet Disord. 2018 Jul 18;19(1):221. doi: 10.1186/s12891-018-2158-8.
15	Intact initiation of autophagy and mitochondrial fission by acute exercise in skeletal muscle of patients with Type2 diabetes.Clin Sci (Lond). 2017 Jan 1;131(1):37-47. doi: 10.1042/CS20160736. Epub 2016 Nov 11.
16	A 9.3 Mb microdeletion of 3q27.3q29 associated with psychomotor and growth delay, tricuspid valve dysplasia and bifid thumb.Eur J Med Genet. 2009 Mar-Jun;52(2-3):131-3. doi: 10.1016/j.ejmg.2009.03.009. Epub 2009 Mar 24.
17	Mapping and genomic characterization of the gene encoding diacylglycerol kinase gamma (DAGK3): assessment of its role in dominant optic atrophy (OPA1).Hum Genet. 1999 Jan;104(1):99-105. doi: 10.1007/s004390050917.
18	Interval and continuous exercise overcome memory deficits related to -Amyloid accumulation through modulating mitochondrial dynamics.Behav Brain Res. 2019 Dec 30;376:112171. doi: 10.1016/j.bbr.2019.112171. Epub 2019 Aug 22.
19	Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. Nat Genet. 2015 Aug;47(8):926-32. doi: 10.1038/ng.3354. Epub 2015 Jul 13.
20	Mitochondrial Morphology, Dynamics, and Function in Human Pressure Overload or Ischemic Heart Disease With Preserved or Reduced Ejection Fraction.Circ Heart Fail. 2019 Feb;12(2):e005131. doi: 10.1161/CIRCHEARTFAILURE.118.005131.
21	Critical role of mitochondrial dysfunction and impaired mitophagy in diabetic nephropathy.J Cell Physiol. 2019 Nov;234(11):19223-19236. doi: 10.1002/jcp.28712. Epub 2019 Apr 29.
22	Testosterone induces up-regulation of mitochondrial gene expression in murine C2C12 skeletal muscle cells accompanied by an increase of nuclear respiratory factor-1 and its downstream effectors.Mol Cell Endocrinol. 2020 Jan 15;500:110631. doi: 10.1016/j.mce.2019.110631. Epub 2019 Oct 30.
23	Protective effect of hyperoside against renal ischemia-reperfusion injury via modulating mitochondrial fission, oxidative stress, and apoptosis.Free Radic Res. 2019 Jul;53(7):727-736. doi: 10.1080/10715762.2019.1623883. Epub 2019 Jun 11.
24	Clinical and molecular genetic findings in autosomal dominant OPA3-related optic neuropathy.Neurogenetics. 2015 Jan;16(1):69-75. doi: 10.1007/s10048-014-0416-y. Epub 2014 Aug 27.
25	Saturating density of STSs (1/6 kb) in a 1.1 Mb region on 3q28-q29: a valuable resource for cloning of disease genes.Eur J Hum Genet. 2001 Apr;9(4):307-10. doi: 10.1038/sj.ejhg.5200630.
26	PGAM5 regulates PINK1/Parkin-mediated mitophagy via DRP1 in CCCP-induced mitochondrial dysfunction.Toxicol Lett. 2018 Mar 1;284:120-128. doi: 10.1016/j.toxlet.2017.12.004. Epub 2017 Dec 11.
27	Genotype-phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal-dominant optic atrophy.Acta Ophthalmol. 2015 Dec;93(8):762-6. doi: 10.1111/aos.12835. Epub 2015 Sep 19.
28	Dominant mutations in mtDNA maintenance gene SSBP1 cause optic atrophy and foveopathy.J Clin Invest. 2020 Jan 2;130(1):143-156. doi: 10.1172/JCI128513.
29	Cyclin-dependent kinase 5 activator p25 is generated during memory formation and is reduced at an early stage in Alzheimer's disease.Biol Psychiatry. 2011 Jul 15;70(2):159-68. doi: 10.1016/j.biopsych.2011.04.011. Epub 2011 May 26.
30	Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage.Hum Mol Genet. 2011 Jul 1;20(13):2495-509. doi: 10.1093/hmg/ddr139. Epub 2011 Mar 31.
31	Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy.Cell Res. 2014 Aug;24(8):977-93. doi: 10.1038/cr.2014.94. Epub 2014 Jul 15.
32	Proteasome dysfunction induces excessive proteome instability and loss of mitostasis that can be mitigated by enhancing mitochondrial fusion or autophagy.Autophagy. 2019 Oct;15(10):1757-1773. doi: 10.1080/15548627.2019.1596477. Epub 2019 Apr 19.
33	Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis in Aprataxin-deficient cells.Nucleic Acids Res. 2019 May 7;47(8):4086-4110. doi: 10.1093/nar/gkz083.