Neuronopathy, distal hereditary motor, autosomal dominant 11

Summary

Neuronopathy, distal hereditary motor, autosomal dominant 11 (MONDO:0957875) is a disease caused by SPTAN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SPTAN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 24

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronopathy, distal hereditary motor, autosomal dominant 11
Mondo ID	MONDO:0957875
OMIM	620528
DOID	DOID:0081400
UMLS	C5882697
MedGen	1849676
GARD	0026889
Is cancer (heuristic)	no

Data availability: 24 ClinVar variants · 1 GenCC gene-disease record.

Disease family

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

Related subtypes (10): neuronopathy, distal hereditary motor, autosomal dominant 1, hereditary spastic paraplegia 17, neuronopathy, distal hereditary motor, autosomal dominant 8, distal hereditary motor neuropathy type 2, distal hereditary motor neuropathy type 7, neuronopathy, distal hereditary motor, type 9, neuronopathy, distal hereditary motor, type 5, neuronopathy, distal hereditary motor, autosomal dominant 10, myopathy, myofibrillar, 13, with rimmed vacuoles, neuronopathy, distal hereditary motor, autosomal dominant 15

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

24 retrieved; paginated sample, class counts are floors:

7 conflicting classifications of pathogenicity, 7 uncertain significance, 4 likely pathogenic, 4 pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2581094	NM_001130438.3(SPTAN1):c.4615C>T (p.Gln1539Ter)	SPTAN1	Pathogenic	no assertion criteria provided
2581095	NM_001130438.3(SPTAN1):c.6367del (p.Val2123fs)	SPTAN1	Pathogenic	no assertion criteria provided
2628105	NM_001130438.3(SPTAN1):c.466C>T (p.Arg156Ter)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664159	NM_001130438.3(SPTAN1):c.3388C>T (p.Gln1130Ter)	SPTAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3385399	NM_001130438.3(SPTAN1):c.3706C>T (p.Gln1236Ter)	SPTAN1	Pathogenic	criteria provided, single submitter
3778735	NM_001130438.3(SPTAN1):c.2848C>T (p.Arg950Ter)	SPTAN1	Pathogenic	criteria provided, single submitter
1065462	NM_001130438.3(SPTAN1):c.415C>T (p.Arg139Ter)	SPTAN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4280639	NM_001130438.3(SPTAN1):c.3290del (p.Phe1097fs)	SPTAN1	Likely pathogenic	criteria provided, single submitter
4759243	NM_001130438.3(SPTAN1):c.6080del (p.Asp2027fs)	SPTAN1	Likely pathogenic	criteria provided, single submitter
4819340	NM_001130438.3(SPTAN1):c.4737dup (p.Lys1580fs)	SPTAN1	Likely pathogenic	criteria provided, single submitter
1275817	NM_001130438.3(SPTAN1):c.6781C>T (p.Arg2261Ter)	SPTAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1419975	NM_001130438.3(SPTAN1):c.6155A>G (p.Lys2052Arg)	SPTAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195806	NM_001130438.3(SPTAN1):c.3414+4T>C	SPTAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1962315	NM_001130438.3(SPTAN1):c.6199A>G (p.Met2067Val)	SPTAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2141001	NM_001130438.3(SPTAN1):c.3781T>C (p.Tyr1261His)	SPTAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
427111	NM_001130438.3(SPTAN1):c.55C>T (p.Arg19Trp)	SPTAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
644023	NM_001130438.3(SPTAN1):c.6494T>C (p.Phe2165Ser)	SPTAN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1433412	NM_001130438.3(SPTAN1):c.2720G>T (p.Arg907Leu)	SPTAN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
198767	NM_001130438.3(SPTAN1):c.958C>T (p.Arg320Cys)	SPTAN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582657	NM_001130438.3(SPTAN1):c.1972A>C (p.Ser658Arg)	SPTAN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3596475	NM_001130438.3(SPTAN1):c.2158C>G (p.His720Asp)	SPTAN1	Uncertain significance	criteria provided, single submitter
3892549	NM_001130438.3(SPTAN1):c.1093C>T (p.Arg365Cys)	SPTAN1	Uncertain significance	criteria provided, single submitter
4082087	NM_001130438.3(SPTAN1):c.4996C>T (p.Gln1666Ter)	SPTAN1	Uncertain significance	criteria provided, single submitter
4849201	NM_001130438.3(SPTAN1):c.1414T>G (p.Phe472Val)	SPTAN1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
SPTAN1	Strong	Autosomal dominant	neuronopathy, distal hereditary motor, autosomal dominant 11	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPTAN1	Orphanet:697160	Infantile epileptic spasms syndrome

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
SPTAN1	HGNC:11273	ENSG00000197694	Q13813	Spectrin alpha chain, non-erythrocytic 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPTAN1	Spectrin alpha chain, non-erythrocytic 1	Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPTAN1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPTAN1	293	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPTAN1	3,083

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPTAN1	Q13813	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. 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
Caspase-mediated cleavage of cytoskeletal proteins	1	951.7×	0.015	SPTAN1
Apoptotic cleavage of cellular proteins	1	475.8×	0.015	SPTAN1
Nephrin family interactions	1	475.8×	0.015	SPTAN1
Apoptotic execution phase	1	475.8×	0.015	SPTAN1
Interaction between L1 and Ankyrins	1	368.4×	0.015	SPTAN1
Sensory processing of sound	1	308.6×	0.015	SPTAN1
RHOV GTPase cycle	1	285.5×	0.015	SPTAN1
RHOU GTPase cycle	1	278.5×	0.015	SPTAN1
NCAM signaling for neurite out-growth	1	271.9×	0.015	SPTAN1
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.018	SPTAN1
Apoptosis	1	167.9×	0.018	SPTAN1
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.018	SPTAN1
Programmed Cell Death	1	146.4×	0.018	SPTAN1
Cell-Cell communication	1	137.6×	0.018	SPTAN1
ER to Golgi Anterograde Transport	1	132.8×	0.018	SPTAN1
MAPK1/MAPK3 signaling	1	131.3×	0.018	SPTAN1
L1CAM interactions	1	120.2×	0.018	SPTAN1
COPI-mediated anterograde transport	1	109.8×	0.018	SPTAN1
MAPK family signaling cascades	1	102.9×	0.018	SPTAN1
Transport to the Golgi and subsequent modification	1	102.9×	0.018	SPTAN1
Sensory Perception	1	95.2×	0.019	SPTAN1
RAF/MAP kinase cascade	1	61.1×	0.026	SPTAN1
Asparagine N-linked glycosylation	1	60.1×	0.026	SPTAN1
RHO GTPase cycle	1	60.1×	0.026	SPTAN1
Axon guidance	1	45.1×	0.033	SPTAN1
Nervous system development	1	42.9×	0.033	SPTAN1
Membrane Trafficking	1	37.1×	0.037	SPTAN1
Vesicle-mediated transport	1	34.8×	0.037	SPTAN1
Signaling by Rho GTPases	1	34.2×	0.037	SPTAN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.037	SPTAN1

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
actin filament capping	1	1532.0×	0.001	SPTAN1
actin cytoskeleton organization	1	79.1×	0.013	SPTAN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SPTAN1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SPTAN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SPTAN1	7	Binding:7

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

1 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)
MOLIBRESIB	2	SPTAN1

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	1	SPTAN1
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: 0.