Optic atrophy 2

Summary

Optic atrophy 2 (MONDO:0010698) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000529	Progressive visual loss	Frequent (30-79%)
HP:0000543	Optic disc pallor	Frequent (30-79%)
HP:0000551	Color vision defect	Frequent (30-79%)
HP:0000603	Central scotoma	Frequent (30-79%)
HP:0000648	Optic atrophy	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000712	Emotional lability	Occasional (5-29%)
HP:0000762	Decreased nerve conduction velocity	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001266	Choreoathetosis	Occasional (5-29%)
HP:0002066	Gait ataxia	Occasional (5-29%)
HP:0002075	Dysdiadochokinesis	Occasional (5-29%)
HP:0002080	Intention tremor	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0012164	Asterixis	Occasional (5-29%)
HP:0012638	Abnormality of nervous system physiology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	optic atrophy 2
Mondo ID	MONDO:0010698
MeSH	C537125
OMIM	311050
Orphanet	98890
DOID	DOID:0111443
SNOMED CT	721200000
UMLS	C1839576
MedGen	326915
GARD	0010199
Is cancer (heuristic)	no

Also known as: non-Leber type optic atrophy with early-onset · OPA2 · optic atrophy 2 · optic atrophy 2, X-linked · optic atrophy type 2

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › optic nerve disorder › optic atrophy › primary optic atrophy › hereditary optic atrophy › optic atrophy 2

Related subtypes (14): optic atrophy 13 with retinal and foveal abnormalities, optic atrophy 6, Leber hereditary optic neuropathy, optic atrophy 4, autosomal recessive optic atrophy, OPA7 type, optic atrophy 11, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, autosomal dominant optic atrophy, optic atrophy 10 with or without ataxia, intellectual disability, and seizures, optic atrophy 12, optic atrophy 14, optic atrophy 15, optic atrophy 16, ACO2-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:

2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1704205	NM_001029896.2(WDR45):c.107C>A (p.Pro36His)	LOC126863256	Likely pathogenic	no assertion criteria provided
1704204	NM_001029896.2(WDR45):c.236-1G>T	WDR45	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR45	Orphanet:329284	Beta-propeller protein-associated neurodegeneration
WDR45	Orphanet:697160	Infantile epileptic spasms syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR45	HGNC:28912	ENSG00000196998	Q9Y484	WD repeat domain phosphoinositide-interacting protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR45	WD repeat domain phosphoinositide-interacting protein 4	Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR45	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
granulocyte	1
mucosa of stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR45	293	ubiquitous	marker	apex of heart, mucosa of stomach, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDR45	1,233

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDR45	Q9Y484	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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
Macroautophagy	1	115.3×	0.009	WDR45

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
nucleophagy	1	3370.4×	0.002	WDR45
glycophagy	1	1404.3×	0.002	WDR45
pexophagy	1	1053.2×	0.002	WDR45
protein localization to phagophore assembly site	1	991.3×	0.002	WDR45
positive regulation of autophagosome assembly	1	802.5×	0.002	WDR45
autophagy of mitochondrion	1	732.7×	0.002	WDR45
autophagosome assembly	1	224.7×	0.006	WDR45
cellular response to starvation	1	193.7×	0.006	WDR45
autophagy	1	110.1×	0.009	WDR45

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
WDR45	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	WDR45

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
WDR45	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.