Demyelinating polyneuropathy

Summary

Demyelinating polyneuropathy (MONDO:0003334) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	demyelinating polyneuropathy
Mondo ID	MONDO:0003334
DOID	DOID:5214
NCIT	C27062
SNOMED CT	23414001
UMLS	C0270922
MedGen	82859
GARD	0023456
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › polyneuropathy › demyelinating polyneuropathy

Related subtypes (9): idiopathic progressive polyneuropathy, polyneuropathy in collagen vascular disease, critical illness polyneuropathy, chronic polyneuropathy, paraneoplastic polyneuropathy, polyradiculoneuropathy, polyneuritis, toxic polyneuropathy, organophosphate-induced delayed polyneuropathy

Subtypes (2): chronic inflammatory demyelinating polyradiculoneuropathy, subacute inflammatory demyelinating polyneuropathy

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
37130	NM_004984.4(KIF5A):c.839G>A (p.Arg280His)	KIF5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342852	NM_020871.4(LRCH2):c.772A>G (p.Lys258Glu)	LRCH2	Pathogenic	no assertion criteria provided
816537	NM_004984.4(KIF5A):c.2005G>A (p.Ala669Thr)	KIF5A	Uncertain significance	criteria provided, single submitter

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
KIF5A	Orphanet:100991	Autosomal dominant spastic paraplegia type 10
KIF5A	Orphanet:324611	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRCH2	HGNC:29292	ENSG00000130224	Q5VUJ6	Leucine-rich repeat and calponin homology domain-containing protein 2	clinvar
KIF5A	HGNC:6323	ENSG00000155980	Q12840	Kinesin heavy chain isoform 5A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRCH2	Leucine-rich repeat and calponin homology domain-containing protein 2	May play a role in the organization of the cytoskeleton.
KIF5A	Kinesin heavy chain isoform 5A	Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL).

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)
LRCH2	Other/Unknown	no		Leu-rich_rpt, CH_dom, Leu-rich_rpt_typical-subtyp
KIF5A	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
cortical plate	1
ganglionic eminence	1
ventricular zone	1
cerebellar hemisphere	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRCH2	207	ubiquitous	marker	ganglionic eminence, cortical plate, ventricular zone
KIF5A	198	broad	marker	right frontal lobe, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF5A	3,241
LRCH2	1,298

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF5A	Q12840	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRCH2	Q5VUJ6	62.83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
RHO GTPases activate KTN1	1	1038.2×	0.018	KIF5A
Insulin processing	1	456.8×	0.021	KIF5A
Peptide hormone metabolism	1	271.9×	0.023	KIF5A
Kinesins	1	178.4×	0.026	KIF5A
Golgi-to-ER retrograde transport	1	132.8×	0.026	KIF5A
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.026	KIF5A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.026	KIF5A
MHC class II antigen presentation	1	89.2×	0.027	KIF5A
RHO GTPase Effectors	1	68.0×	0.029	KIF5A
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.029	KIF5A
Membrane Trafficking	1	37.1×	0.038	KIF5A
Hemostasis	1	36.0×	0.038	KIF5A
Vesicle-mediated transport	1	34.8×	0.038	KIF5A
Signaling by Rho GTPases	1	34.2×	0.038	KIF5A
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.038	KIF5A
Adaptive Immune System	1	29.8×	0.040	KIF5A
Immune System	1	13.0×	0.085	KIF5A
Metabolism of proteins	1	12.4×	0.085	KIF5A
Signal Transduction	1	10.2×	0.098	KIF5A

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
retrograde neuronal dense core vesicle transport	1	3370.4×	0.001	KIF5A
anterograde dendritic transport of neurotransmitter receptor complex	1	2407.4×	0.001	KIF5A
anterograde axonal protein transport	1	2106.5×	0.001	KIF5A
synaptic vesicle transport	1	842.6×	0.002	KIF5A
microtubule-based movement	1	295.6×	0.005	KIF5A
vesicle-mediated transport	1	96.3×	0.013	KIF5A
axon guidance	1	90.6×	0.013	KIF5A
chemical synaptic transmission	1	77.3×	0.013	KIF5A

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
LRCH2	0	0
KIF5A	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
KIF5A	8	Binding:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	LRCH2, KIF5A

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)
LRCH2	0	—
KIF5A	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01349270	PHASE3	COMPLETED	Randomized Open-label Trial to Compare Efficacy and Tolerance of Corticosteroids and IVIg

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CHEMBL15720	0	1