Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity

Summary

Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity (MONDO:0971150) is a disease caused by RTN2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RTN2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity
Mondo ID	MONDO:0971150
OMIM	620854
UMLS	C5935630
MedGen	1856205
GARD	0027204
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › neuronopathy, distal hereditary motor, autosomal recessive › neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity

Related subtypes (11): autosomal recessive distal spinal muscular atrophy 1, autosomal recessive distal spinal muscular atrophy 2, neuronopathy, distal hereditary motor, autosomal recessive 3, neuronopathy, distal hereditary motor, autosomal recessive 4, neuronopathy, distal hereditary motor, autosomal recessive 5, neuronopathy, distal hereditary motor, autosomal recessive 8, neuronopathy, distal hereditary motor, autosomal recessive 7, early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome, spinal muscular atrophy, distal, autosomal recessive, 6, neuronopathy, distal hereditary motor, autosomal recessive 9, neuronopathy, distal hereditary motor, autosomal recessive 10

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

5 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
30324	NM_005619.5(RTN2):c.178dup (p.Arg60fs)	RTN2	Pathogenic	no assertion criteria provided
3248641	NM_005619.5(RTN2):c.287del (p.Pro96fs)	RTN2	Pathogenic	no assertion criteria provided
3248642	NM_005619.5(RTN2):c.701_702dup (p.Leu235fs)	RTN2	Pathogenic	no assertion criteria provided
3248643	NM_005619.5(RTN2):c.79G>T (p.Gly27Ter)	RTN2	Pathogenic	no assertion criteria provided
548603	NM_005619.5(RTN2):c.938dup (p.Thr314fs)	RTN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
RTN2	Strong	Autosomal recessive	neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RTN2	Orphanet:100993	Autosomal dominant spastic paraplegia type 12

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
RTN2	HGNC:10468	ENSG00000125744	O75298	Reticulon-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RTN2	Reticulon-2	Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.

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)
RTN2	Other/Unknown	no		Reticulon, RTN1-4

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
gastrocnemius	1
hindlimb stylopod muscle	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RTN2	271	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, hindlimb stylopod muscle, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RTN2	1,343

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RTN2	O75298	50.99

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
intracellular protein transmembrane transport	1	5617.3×	9e-04	RTN2
endoplasmic reticulum tubular network formation	1	2808.7×	9e-04	RTN2
regulation of D-glucose import across plasma membrane	1	2106.5×	9e-04	RTN2
endoplasmic reticulum tubular network membrane organization	1	2106.5×	9e-04	RTN2
negative regulation of amyloid-beta formation	1	887.0×	0.002	RTN2
neuron differentiation	1	100.3×	0.013	RTN2
gene expression	1	79.9×	0.013	RTN2
brain development	1	79.5×	0.013	RTN2

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
RTN2	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	RTN2

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)
RTN2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.