Amyotrophic neuralgia

Summary

Amyotrophic neuralgia (MONDO:0008076) is a disease caused by SEPTIN9 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: SEPTIN9 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 136
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic neuralgia
Mondo ID	MONDO:0008076
OMIM	162100
DOID	DOID:10383
SNOMED CT	26609002
UMLS	C1834304
MedGen	320318
GARD	0003955
Is cancer (heuristic)	no

Also known as: amyotrophy, hereditary neuralgic · amyotrophy, hereditary neuralgic, with predilection for brachial plexus · brachial plexus neuropathy, hereditary · hereditary brachial plexus neuropathy · hereditary neuralgic amyotrophy · HNA · neuralgic amyotrophy · neuritis with brachial predilection

Data availability: 136 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › nerve plexus disorder › brachial plexus neuropathy › amyotrophic neuralgia

Related subtypes (6): radial neuropathy, median nerve neuropathy, brachial plexus neoplasm, brachial plexus neuropathy from injury, brachial plexus neuritis, ulnar neuropathy

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

136 retrieved; paginated sample, class counts are floors:

51 benign, 42 uncertain significance, 19 benign/likely benign, 17 conflicting classifications of pathogenicity, 4 pathogenic, 3 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
5866	NG_011683.2:g.92552_130155dup	LOC130061758	Pathogenic	no assertion criteria provided
5863	NM_001113491.2(SEPTIN9):c.316C>T (p.Arg106Trp)	SEPTIN9	Pathogenic	criteria provided, multiple submitters, no conflicts
5864	NM_001113491.2(SEPTIN9):c.332C>T (p.Ser111Phe)	SEPTIN9	Pathogenic	no assertion criteria provided
5865	NM_001113491.2(SEPTIN9):c.76+12996G>C	SEPTIN9	Pathogenic	no assertion criteria provided
325531	NM_001113491.2(SEPTIN9):c.76+12764G>A	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325544	NM_001113491.2(SEPTIN9):c.442C>T (p.Arg148Trp)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325545	NM_001113491.2(SEPTIN9):c.519C>T (p.Pro173=)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325546	NM_001113491.2(SEPTIN9):c.538G>A (p.Ala180Thr)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325548	NM_001113491.2(SEPTIN9):c.710G>A (p.Arg237Gln)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325554	NM_001113491.2(SEPTIN9):c.1042G>A (p.Asp348Asn)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325560	NM_001113491.2(SEPTIN9):c.1320C>G (p.Val440=)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325602	NM_001113491.2(SEPTIN9):c.*903C>T	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325613	NM_001113491.2(SEPTIN9):c.*1639C>G	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
446761	NM_001113491.2(SEPTIN9):c.353_354delinsCC (p.Gln118Pro)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
734847	NM_001113491.2(SEPTIN9):c.619A>G (p.Thr207Ala)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
756206	NM_001113491.2(SEPTIN9):c.1063C>T (p.Arg355Trp)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
812141	NM_001113491.2(SEPTIN9):c.1460T>C (p.Val487Ala)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889089	NM_001113491.2(SEPTIN9):c.907G>A (p.Val303Met)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889785	NM_001113491.2(SEPTIN9):c.1124+8C>T	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
891278	NM_001113491.2(SEPTIN9):c.146C>A (p.Thr49Asn)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
892527	NM_001113491.2(SEPTIN9):c.1699G>A (p.Glu567Lys)	SEPTIN9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2435813	NM_001113491.2(SEPTIN9):c.1381-4C>G	SEPTIN9	Uncertain significance	criteria provided, single submitter
2689940	NM_001113491.2(SEPTIN9):c.1166A>G (p.Lys389Arg)	SEPTIN9	Uncertain significance	criteria provided, single submitter
2689941	NM_001113491.2(SEPTIN9):c.362A>G (p.Asn121Ser)	SEPTIN9	Uncertain significance	criteria provided, single submitter
325527	NM_001113491.2(SEPTIN9):c.76+12350G>C	SEPTIN9	Uncertain significance	criteria provided, single submitter
325529	NM_001113491.2(SEPTIN9):c.76+12407G>A	SEPTIN9	Uncertain significance	criteria provided, single submitter
325532	NM_001113491.2(SEPTIN9):c.76+12793G>A	SEPTIN9	Uncertain significance	criteria provided, single submitter
325537	NM_001113491.2(SEPTIN9):c.134G>A (p.Arg45Gln)	SEPTIN9	Uncertain significance	criteria provided, multiple submitters, no conflicts
325538	NM_001113491.2(SEPTIN9):c.158G>A (p.Arg53Gln)	SEPTIN9	Uncertain significance	criteria provided, single submitter
325540	NM_001113491.2(SEPTIN9):c.202G>A (p.Val68Met)	SEPTIN9	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
SEPTIN9	Strong	Autosomal dominant	amyotrophic neuralgia	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEPTIN9	Orphanet:2901	Neuralgic amyotrophy

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
SEPTIN9	HGNC:7323	ENSG00000184640	Q9UHD8	Septin-9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEPTIN9	Septin-9	Filament-forming cytoskeletal GTPase.

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)
SEPTIN9	Other/Unknown	no		Septin, P-loop_NTPase, G_SEPTIN_dom

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
granulocyte	1
ileal mucosa	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEPTIN9	293	ubiquitous	marker	ileal mucosa, granulocyte, thymus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SEPTIN9	2,119

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SEPTIN9	Q9UHD8	3

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
septin cytoskeleton organization	1	4213.0×	0.001	SEPTIN9
positive regulation of non-motile cilium assembly	1	1872.4×	0.001	SEPTIN9
cytoskeleton-dependent cytokinesis	1	802.5×	0.002	SEPTIN9
intracellular protein localization	1	104.7×	0.012	SEPTIN9
actin cytoskeleton organization	1	79.1×	0.013	SEPTIN9

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SEPTIN9	BARICITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SEPTIN9	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BARICITINIB	4	SEPTIN9
TANDUTINIB	2	SEPTIN9
UCN-01	2	SEPTIN9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SEPTIN9	2	Binding:2

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
BARICITINIB	4	SEPTIN9
TANDUTINIB	2	SEPTIN9
UCN-01	2	SEPTIN9

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SEPTIN9
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03441347	Not specified	COMPLETED	Neuralgic Amyotrophy: Central Reorganization and Rehabilitation After Peripheral Dysfunction