Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy

Summary

Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy (MONDO:0018576) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• Phenotypes (HPO): 38

Clinical features

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0006980	Progressive leukoencephalopathy	Very frequent (80-99%)
HP:0007133	Progressive peripheral neuropathy	Very frequent (80-99%)
HP:0000093	Proteinuria	Frequent (30-79%)
HP:0000124	Renal tubular dysfunction	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000580	Pigmentary retinopathy	Frequent (30-79%)
HP:0000648	Optic atrophy	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001262	Excessive daytime somnolence	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001410	Decreased liver function	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001639	Hypertrophic cardiomyopathy	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001994	Renal Fanconi syndrome	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0002490	Increased CSF lactate	Frequent (30-79%)
HP:0002747	Respiratory insufficiency due to muscle weakness	Frequent (30-79%)
HP:0002875	Exertional dyspnea	Frequent (30-79%)
HP:0003076	Glycosuria	Frequent (30-79%)
HP:0003109	Hyperphosphaturia	Frequent (30-79%)
HP:0003128	Lactic acidosis	Frequent (30-79%)
HP:0003324	Generalized muscle weakness	Frequent (30-79%)
HP:0003355	Aminoaciduria	Frequent (30-79%)
HP:0006555	Diffuse hepatic steatosis	Frequent (30-79%)
HP:0007256	Abnormal pyramidal sign	Frequent (30-79%)
HP:0008619	Bilateral sensorineural hearing impairment	Frequent (30-79%)
HP:0030195	Fatigable weakness of swallowing muscles	Frequent (30-79%)
HP:0040291	Skeletal muscle steatosis	Frequent (30-79%)
HP:0001285	Spastic tetraparesis	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy
Mondo ID	MONDO:0018576
Orphanet	436271
UMLS	C5688227
MedGen	1806079
GARD	0021819
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy

Related subtypes (47): mitochondrial respiratory chain complex deficiency, combined oxidative phosphorylation deficiency, myopathy, lactic acidosis, and sideroblastic anemia, optic atrophy 3, autosomal dominant optic atrophy, classic form, Leigh syndrome, mitochondrial non-syndromic sensorineural hearing loss, maternally-inherited diabetes and deafness, chronic diarrhea with villous atrophy, Kearns-Sayre syndrome, Leber hereditary optic neuropathy, NARP syndrome, deafness, aminoglycoside-induced, hereditary spastic paraplegia 7, spinocerebellar ataxia type 28, leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome, spastic ataxia 3, pontocerebellar hypoplasia type 6, autosomal recessive optic atrophy, OPA7 type, acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins, congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome, spastic ataxia 4, hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome, hereditary spastic paraplegia 55, cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, Charcot-Marie-Tooth disease recessive intermediate D, autosomal dominant mitochondrial myopathy with exercise intolerance, Charcot-Marie-Tooth disease type 4K, hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome, hereditary spastic paraplegia 77, fatal infantile encephalocardiomyopathy, FASTKD2-related infantile mitochondrial encephalomyopathy, autosomal dominant optic atrophy and peripheral neuropathy, ataxia neuropathy spectrum, maternally-inherited mitochondrial dystonia, Perrault syndrome, hypertrophic cardiomyopathy and renal tubular disease due to mitochondrial DNA mutation, adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy, mitochondrial DNA maintenance syndrome, coenzyme Q10 deficiency, mitochondrial DNA depletion syndrome, periodic paralysis with later-onset distal motor neuropathy, Zellweger-like syndrome without peroxisomal anomalies, maternally-inherited progressive external ophthalmoplegia, Leber plus disease, encephalopathy due to mitochondrial and peroxisomal fission defect, severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
COA8	Supportive	Autosomal recessive	non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COA8	Orphanet:436271	Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy

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
COA8	HGNC:20492	ENSG00000256053	Q96IL0	Cytochrome c oxidase assembly factor 8	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COA8	Cytochrome c oxidase assembly factor 8	Required for cytochrome c complex (COX) IV assembly and function Protects COX assembly from oxidation-induced degradation, COX being the terminal component of the mitochondrial respiratory chain.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COA8	Other/Unknown	no		COA8

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
hindlimb stylopod muscle	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COA8	248	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COA8	227

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COA8	Q96IL0	81.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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 reactive oxygen species	1	1053.2×	0.003	COA8
mitochondrial respiratory chain complex IV assembly	1	624.1×	0.003	COA8
intrinsic apoptotic signaling pathway	1	358.6×	0.004	COA8
protein stabilization	1	66.9×	0.015	COA8

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
COA8	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	COA8

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)
COA8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.