Hereditary optic neuropathy
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Summary
Hereditary optic neuropathy (MONDO:0020249) is a disease (an umbrella term covering 8 Mondo subtypes) with 2 cohort genes and 1 clinical trial.
At a glance
- Umbrella term: 8 Mondo subtypes
- Cohort genes: 2
- ClinVar variants: 2
- Clinical trials: 1
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hereditary optic neuropathy |
| Mondo ID | MONDO:0020249 |
| Orphanet | 98671 |
| ICD-11 | 2452831 |
| GARD | 0019540 |
| MedDRA | 10061323 |
| Is cancer (heuristic) | no |
Data availability: 2 ClinVar variants · 5 cell lines.
Disease family
An umbrella term covering 8 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › hereditary optic neuropathy
Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia
Subtypes (8): isolated optic nerve hypoplasia, Leber hereditary optic neuropathy, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome, morning glory syndrome, autosomal recessive osteopetrosis, autosomal dominant optic atrophy, OPA1-related optic atrophy with or without extraocular features
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
2 retrieved; paginated sample, class counts are floors:
1 conflicting classifications of pathogenicity, 1 uncertain significance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 4072164 | NM_014208.3(DSPP):c.3267_3401del (p.Asn1092_Ser1136del) | DMP1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 4075101 | NC_012920.1(MT-ND3):m.10290G>A | MT-ND3 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MT-ND3 | Orphanet:255210 | Mitochondrial DNA-associated Leigh syndrome |
| MT-ND3 | Orphanet:2609 | Isolated complex I deficiency |
| MT-ND3 | Orphanet:99718 | Leber plus disease |
Cohort genes → proteins
2 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| DMP1-AS1 | HGNC:58144 | ENSG00000249001 | DMP1 and DSPP antisense RNA 1 | clinvar | |
| MT-ND3 | HGNC:7458 | ENSG00000198840 | P03897 | NADH-ubiquinone oxidoreductase chain 3 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MT-ND3 | NADH-ubiquinone oxidoreductase chain 3 | Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 2 | 1.8× | 0.312 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| DMP1-AS1 | Other/Unknown | no | ||
| MT-ND3 | Other/Unknown | no | NADH_UbQ/plastoQ_OxRdtase_su3, NDAH_ubi_oxred_su3_sf |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| ganglionic eminence | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| sperm | 1 |
| adipose tissue | 1 |
| granulocyte | 1 |
| left lobe of thyroid gland | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| DMP1-AS1 | 108 | yes | male germ line stem cell (sensu Vertebrata) in testis, sperm, ganglionic eminence | |
| MT-ND3 | 134 | ubiquitous | marker | granulocyte, adipose tissue, left lobe of thyroid gland |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MT-ND3 | 2,923 |
| DMP1-AS1 | 0 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| MT-ND3 | P03897 | 5 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Complex I biogenesis | 1 | 165.5× | 0.011 | MT-ND3 |
| Mitochondrial translation termination | 1 | 109.8× | 0.011 | MT-ND3 |
| Respiratory electron transport | 1 | 95.2× | 0.011 | MT-ND3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| response to light intensity | 1 | 2106.5× | 0.003 | MT-ND3 |
| cellular response to glucocorticoid stimulus | 1 | 624.1× | 0.005 | MT-ND3 |
| mitochondrial electron transport, NADH to ubiquinone | 1 | 358.6× | 0.005 | MT-ND3 |
| proton motive force-driven mitochondrial ATP synthesis | 1 | 263.3× | 0.005 | MT-ND3 |
| aerobic respiration | 1 | 247.8× | 0.005 | MT-ND3 |
| response to oxidative stress | 1 | 130.6× | 0.008 | MT-ND3 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| DMP1-AS1 | 0 | 0 |
| MT-ND3 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| MT-ND3 | 4 | Binding:4 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | DMP1-AS1, MT-ND3 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| DMP1-AS1 | 0 | — |
| MT-ND3 | 4 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05353413 | Not specified | UNKNOWN | Diffusion Weighted Magnetic Resonance Imaging and the Optic Nerve Neuropathy. |