Leukoencephalopathy without lacunae, adult-onset

Summary

Leukoencephalopathy without lacunae, adult-onset (MONDO:0980752) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	leukoencephalopathy without lacunae, adult-onset
Mondo ID	MONDO:0980752
OMIM	621424
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › leukodystrophy › leukoencephalopathy without lacunae, adult-onset

Related subtypes (64): Alexander disease, cerebrotendinous xanthomatosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, dermatoleukodystrophy, Krabbe disease, Sjogren-Larsson syndrome, Canavan disease, Pelizaeus-Merzbacher spectrum disorder, hereditary spastic paraplegia 2, megalencephalic leukoencephalopathy with subcortical cysts, ribose-5-P isomerase deficiency, hypomyelinating leukodystrophy 5, leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome, hypomyelinating leukodystrophy 6, cystic leukoencephalopathy without megalencephaly, sterol carrier protein 2 deficiency, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome, hypomyelination with brain stem and spinal cord involvement and leg spasticity, leukoencephalopathy with mild cerebellar ataxia and white matter edema, progressive encephalopathy with leukodystrophy due to DECR deficiency, hypomyelinating leukodystrophy 9, multiple mitochondrial dysfunctions syndrome 4, hypomyelinating leukodystrophy 10, hypomyelinating leukodystrophy 12, hypomyelinating leukodystrophy 13, leukoencephalopathy with bilateral anterior temporal lobe cysts, progressive cavitating leukoencephalopathy, Pelizaeus-Merzbacher-like disease, CADDS, adrenoleukodystrophy, non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy, Aicardi-Goutieres syndrome, metachromatic leukodystrophy, peroxisome biogenesis disorder, unknown leukodystrophy, ravine syndrome, leukodystrophy, hypomyelinating, 22, leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, leukodystrophy, hypomyelinating, 18, leukodystrophy, hypomyelinating, 19, transient infantile, spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 14, leukodystrophy, hypomyelinating, 20, early-onset calcifying leukoencephalopathy-skeletal dysplasia, c11orf73-related autosomal recessive hypomyelinating leukodystrophy, alkaline ceramidase 3 deficiency, leukodystrophy, hypomyelinating, 15, leukodystrophy, hypomyelinating, 16, leukodystrophy, hypomyelinating, 17, POLR-related leukodystrophy, leukoencephalopathy, diffuse hereditary, with spheroids 1, leukoencephalopathy with vanishing white matter, leukodystrophy, hypomyelinating, 24, leukodystrophy, childhood-onset, remitting, leukodystrophy, hypomyelinating, 25, leukodystrophy, hypomyelinating, 26, with chondrodysplasia, adult-onset progressive leukoencephalopathy-early-onset deafness, leukoencephalopathy, porphyria-related, episodic memory defect leukoencephalopathy, leukodystrophy, hypomyelinating, 28, leukodystrophy, demyelinating, adult-onset, leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy, AARS1-related leukoencephalopathy

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
4531161	NM_002291.3(LAMB1):c.5250_5253del (p.Asn1750fs)	LAMB1	Pathogenic	no assertion criteria provided
4531163	NM_002291.3(LAMB1):c.5123_5124delinsT (p.Lys1708fs)	LAMB1	Pathogenic	no assertion criteria provided
4531164	NM_002291.3(LAMB1):c.5161dup (p.Met1721fs)	LAMB1	Pathogenic	no assertion criteria provided
1366041	NM_002291.3(LAMB1):c.5188_5189del (p.Leu1730fs)	LAMB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMB1	Orphanet:352682	Cobblestone lissencephaly without muscular or ocular involvement

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
LAMB1	HGNC:6486	ENSG00000091136	P07942	Laminin subunit beta-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LAMB1	Laminin subunit beta-1	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

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)
LAMB1	Other/Unknown	no		EGF, LE_dom, Laminin_N

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
nerve	1
omental fat pad	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMB1	284	ubiquitous	marker	nerve, tibial nerve, omental fat pad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMB1	1,970

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LAMB1	P07942	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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
MET promotes cell motility	1	601.0×	0.010	LAMB1
Attachment of bacteria to epithelial cells	1	496.5×	0.010	LAMB1
Laminin interactions	1	380.7×	0.010	LAMB1
MET activates PTK2 signaling	1	380.7×	0.010	LAMB1
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.010	LAMB1
Signaling by MET	1	317.2×	0.010	LAMB1
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.010	LAMB1
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.012	LAMB1
Non-integrin membrane-ECM interactions	1	154.3×	0.015	LAMB1
ECM proteoglycans	1	150.3×	0.015	LAMB1
L1CAM interactions	1	120.2×	0.016	LAMB1
Degradation of the extracellular matrix	1	117.7×	0.016	LAMB1
Post-translational protein phosphorylation	1	100.2×	0.017	LAMB1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.018	LAMB1
Extracellular matrix organization	1	63.1×	0.023	LAMB1
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.027	LAMB1
Axon guidance	1	45.1×	0.028	LAMB1
Nervous system development	1	42.9×	0.028	LAMB1
Post-translational protein modification	1	19.2×	0.060	LAMB1
Developmental Biology	1	14.5×	0.076	LAMB1
Metabolism of proteins	1	12.4×	0.085	LAMB1
Signal Transduction	1	10.2×	0.098	LAMB1

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
neuronal-glial interaction involved in cerebral cortex radial glia guided migration	1	16852.0×	0.001	LAMB1
regulation of basement membrane organization	1	2808.7×	0.003	LAMB1
positive regulation of integrin-mediated signaling pathway	1	1296.3×	0.004	LAMB1
positive regulation of muscle cell differentiation	1	1123.5×	0.004	LAMB1
odontogenesis	1	526.6×	0.005	LAMB1
endodermal cell differentiation	1	495.6×	0.005	LAMB1
negative regulation of cell adhesion	1	383.0×	0.005	LAMB1
embryo implantation	1	351.1×	0.005	LAMB1
substrate adhesion-dependent cell spreading	1	343.9×	0.005	LAMB1
regulation of embryonic development	1	330.4×	0.005	LAMB1
regulation of cell adhesion	1	306.4×	0.005	LAMB1
positive regulation of cell adhesion	1	271.8×	0.006	LAMB1
positive regulation of epithelial cell proliferation	1	244.2×	0.006	LAMB1
regulation of cell migration	1	157.5×	0.008	LAMB1
neuron projection development	1	122.1×	0.010	LAMB1
positive regulation of cell migration	1	61.7×	0.018	LAMB1
cell adhesion	1	37.5×	0.028	LAMB1
signal transduction	1	16.1×	0.062	LAMB1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LAMB1	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
LAMB1	1	Binding:1

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	LAMB1

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)
LAMB1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.