neuronopathy, distal hereditary motor, type 7B

Summary

neuronopathy, distal hereditary motor, type 7B (MONDO:0011879) is a disease caused by DCTN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DCTN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1,358

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronopathy, distal hereditary motor, type 7B
Mondo ID	MONDO:0011879
MeSH	C564362
OMIM	607641
DOID	DOID:0111202
UMLS	C1843315
MedGen	375157
GARD	0018270
Is cancer (heuristic)	no

Also known as: DCTN1 neuronopathy, distal hereditary motor · HMN7B · neuronopathy, distal hereditary motor caused by mutation in DCTN1 · neuronopathy, distal hereditary motor, type VIIB

Data availability: 1,358 ClinVar variants · 4 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 dominant disease › neuronopathy, distal hereditary motor, autosomal dominant › distal hereditary motor neuropathy type 7 › neuronopathy, distal hereditary motor, type 7B

Related subtypes (1): neuronopathy, distal hereditary motor, type 7A

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

600 retrieved; paginated sample, class counts are floors:

276 likely benign, 274 uncertain significance, 22 conflicting classifications of pathogenicity, 12 benign, 10 benign/likely benign, 4 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1458171	NM_004082.5(DCTN1):c.175G>C (p.Gly59Arg)	DCTN1	Pathogenic	criteria provided, single submitter
1929273	NM_004082.5(DCTN1):c.626dup (p.Leu210fs)	DCTN1	Pathogenic	criteria provided, single submitter
21390	NM_004082.5(DCTN1):c.212G>A (p.Gly71Glu)	DCTN1	Pathogenic	criteria provided, multiple submitters, no conflicts
2499593	NM_004082.5(DCTN1):c.279+2T>C	DCTN1	Pathogenic	criteria provided, single submitter
2575870	NM_004082.5(DCTN1):c.279G>C (p.Gln93His)	DCTN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1474510	NM_004082.5(DCTN1):c.3823C>T (p.Arg1275Cys)	DCTN1	Likely pathogenic	criteria provided, single submitter
1004603	NM_004082.5(DCTN1):c.2015+3A>G	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1063146	NM_004082.5(DCTN1):c.200G>T (p.Gly67Val)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1113107	NM_004082.5(DCTN1):c.2761-5C>T	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1140099	NM_004082.5(DCTN1):c.280-5C>T	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1350995	NM_004082.5(DCTN1):c.3334A>G (p.Ser1112Gly)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1381056	NM_004082.5(DCTN1):c.432+1G>T	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1387060	NM_004082.5(DCTN1):c.3796C>A (p.Gln1266Lys)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1393318	NM_004082.5(DCTN1):c.2426A>T (p.Asp809Val)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1400346	NM_004082.5(DCTN1):c.2681A>G (p.Asn894Ser)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1423635	NM_004082.5(DCTN1):c.3529+3A>G	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1430404	NM_004082.5(DCTN1):c.1490G>A (p.Arg497His)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1480845	NM_004082.5(DCTN1):c.613G>C (p.Gly205Arg)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1482795	NM_004082.5(DCTN1):c.73C>T (p.Arg25Trp)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1508966	NM_004082.5(DCTN1):c.1082A>G (p.Lys361Arg)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1729506	NM_004082.5(DCTN1):c.325C>A (p.Pro109Thr)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1733017	NM_004082.5(DCTN1):c.359-6C>T	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1790531	NM_004082.5(DCTN1):c.2389T>C (p.Phe797Leu)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1793978	NM_004082.5(DCTN1):c.2623G>A (p.Glu875Lys)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2080849	NM_004082.5(DCTN1):c.3700-6C>A	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
259232	NM_004082.5(DCTN1):c.1484G>A (p.Arg495Gln)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282607	NM_004082.5(DCTN1):c.414+1G>A	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287304	NM_004082.5(DCTN1):c.1692C>T (p.Ala564=)	DCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001699	NM_004082.5(DCTN1):c.1179G>C (p.Lys393Asn)	DCTN1	Uncertain significance	criteria provided, single submitter
1002106	NM_004082.5(DCTN1):c.2089C>T (p.Arg697Cys)	DCTN1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 3 · 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
DCTN1	Strong	Autosomal dominant	neuronopathy, distal hereditary motor, type 7B	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCTN1	Orphanet:139589	Distal hereditary motor neuropathy type 7
DCTN1	Orphanet:178509	Perry syndrome
DCTN1	Orphanet:803	Amyotrophic lateral sclerosis

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
DCTN1	HGNC:2711	ENSG00000204843	Q14203	Dynactin subunit 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCTN1	Dynactin subunit 1	Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.

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)
DCTN1	Other/Unknown	no		CAP-Gly_domain, Dynactin, CAP-Gly_dom_sf

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
prefrontal cortex	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCTN1	275	ubiquitous	marker	right frontal lobe, prefrontal cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DCTN1	3,654

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCTN1	Q14203	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
XBP1(S) activates chaperone genes	1	215.5×	0.010	DCTN1
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.010	DCTN1
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	193.6×	0.010	DCTN1
Loss of Nlp from mitotic centrosomes	1	158.6×	0.010	DCTN1
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.010	DCTN1
AURKA Activation by TPX2	1	152.3×	0.010	DCTN1
Signaling by ALK fusions and activated point mutants	1	150.3×	0.010	DCTN1
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.010	DCTN1
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.010	DCTN1
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.010	DCTN1
Anchoring of the basal body to the plasma membrane	1	113.1×	0.010	DCTN1
COPI-mediated anterograde transport	1	109.8×	0.010	DCTN1
MHC class II antigen presentation	1	89.2×	0.011	DCTN1

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
positive regulation of neuromuscular junction development	1	8426.0×	0.002	DCTN1
positive regulation of microtubule nucleation	1	2106.5×	0.002	DCTN1
mitotic nuclear membrane disassembly	1	1872.4×	0.002	DCTN1
ventral spinal cord development	1	1872.4×	0.002	DCTN1
maintenance of synapse structure	1	1532.0×	0.002	DCTN1
microtubule anchoring at centrosome	1	1404.3×	0.002	DCTN1
centriole-centriole cohesion	1	1296.3×	0.002	DCTN1
neuron projection maintenance	1	1123.5×	0.002	DCTN1
regulation of mitotic spindle organization	1	842.6×	0.003	DCTN1
melanosome transport	1	766.0×	0.003	DCTN1
nuclear migration	1	732.7×	0.003	DCTN1
positive regulation of microtubule polymerization	1	674.1×	0.003	DCTN1
motor behavior	1	561.7×	0.003	DCTN1
neuromuscular junction development	1	526.6×	0.003	DCTN1
neuromuscular process	1	526.6×	0.003	DCTN1
establishment of mitotic spindle orientation	1	481.5×	0.003	DCTN1
neuron cellular homeostasis	1	455.5×	0.003	DCTN1
non-motile cilium assembly	1	290.6×	0.004	DCTN1
retrograde transport, endosome to Golgi	1	205.5×	0.006	DCTN1
mitotic cell cycle	1	133.8×	0.008	DCTN1
cell division	1	46.2×	0.022	DCTN1
nervous system development	1	45.9×	0.022	DCTN1

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
DCTN1	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
DCTN1	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	DCTN1

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)
DCTN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.