Distal hereditary motor neuropathy type 7

Summary

Distal hereditary motor neuropathy type 7 (MONDO:0015355) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	distal hereditary motor neuropathy type 7
Mondo ID	MONDO:0015355
Orphanet	139589
DOID	DOID:0111199
ICD-11	80361835
UMLS	C4749653
MedGen	1662655
GARD	0016960
Is cancer (heuristic)	no

Also known as: dHMN7 · distal spinal muscular atrophy with vocal cord paralysis

Data availability: 2 GenCC gene-disease records · 5 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

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, neuronopathy, distal hereditary motor, type 9, neuronopathy, distal hereditary motor, type 5, neuronopathy, distal hereditary motor, autosomal dominant 10, neuronopathy, distal hereditary motor, autosomal dominant 11, myopathy, myofibrillar, 13, with rimmed vacuoles, neuronopathy, distal hereditary motor, autosomal dominant 15

Subtypes (2): neuronopathy, distal hereditary motor, type 7A, neuronopathy, distal hereditary motor, type 7B

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 5 · 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
SLC5A7	Strong	Autosomal dominant	neuronopathy, distal hereditary motor, type 7A	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC5A7	Orphanet:139589	Distal hereditary motor neuropathy type 7
SLC5A7	Orphanet:98914	Presynaptic congenital myasthenic syndromes
DCTN1	Orphanet:139589	Distal hereditary motor neuropathy type 7
DCTN1	Orphanet:178509	Perry syndrome
DCTN1	Orphanet:803	Amyotrophic lateral sclerosis

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
SLC5A7	HGNC:14025	ENSG00000115665	Q9GZV3	High affinity choline transporter 1	gencc
DCTN1	HGNC:2711	ENSG00000204843	Q14203	Dynactin subunit 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC5A7	High affinity choline transporter 1	High-affinity Na(+)-coupled choline transmembrane symporter.
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: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC5A7	Transporter	yes		Na/solute_symporter, Na/Glc_symporter_sf, Choline_transporter
DCTN1	Other/Unknown	no		CAP-Gly_domain, Dynactin, CAP-Gly_dom_sf

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
male germ line stem cell (sensu Vertebrata) in testis	1
pancreatic ductal cell	1
primordial germ cell in gonad	1
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
SLC5A7	101	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, primordial germ cell in gonad
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
SLC5A7	1,536

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCTN1	Q14203	13
SLC5A7	Q9GZV3	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC5A7 in the neurotransmitter release cycle causes distal hereditary motor neuronopathy 7A (HMN7A)	1	5710.0×	0.002	SLC5A7
Defective transport by SLC5A7 causes distal hereditary motor neuronopathy 7A (HMN7A)	1	5710.0×	0.002	SLC5A7
SLC-mediated bile acid transport	1	815.7×	0.011	SLC5A7
Acetylcholine Neurotransmitter Release Cycle	1	335.9×	0.019	SLC5A7
Neurotransmitter release cycle	1	219.6×	0.024	SLC5A7
XBP1(S) activates chaperone genes	1	107.7×	0.024	DCTN1
COPI-independent Golgi-to-ER retrograde traffic	1	103.8×	0.024	DCTN1
SLC transporter disorders	1	102.0×	0.024	SLC5A7
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	96.8×	0.024	DCTN1
R-HSA-425366	1	90.6×	0.024	SLC5A7
Loss of Nlp from mitotic centrosomes	1	79.3×	0.024	DCTN1
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.024	DCTN1
AURKA Activation by TPX2	1	76.1×	0.024	DCTN1
Signaling by ALK fusions and activated point mutants	1	75.1×	0.024	DCTN1
Disorders of transmembrane transporters	1	69.6×	0.024	SLC5A7
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.024	DCTN1
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.024	DCTN1
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.024	DCTN1
Anchoring of the basal body to the plasma membrane	1	56.5×	0.024	DCTN1
COPI-mediated anterograde transport	1	54.9×	0.024	DCTN1
MHC class II antigen presentation	1	44.6×	0.028	DCTN1
Transmission across Chemical Synapses	1	38.1×	0.031	SLC5A7
SLC-mediated transmembrane transport	1	29.6×	0.038	SLC5A7
Neuronal System	1	22.1×	0.048	SLC5A7
Transport of small molecules	1	12.6×	0.081	SLC5A7
Disease	1	6.5×	0.147	SLC5A7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	4213.0×	0.005	DCTN1
acetylcholine biosynthetic process	1	2808.7×	0.005	SLC5A7
positive regulation of microtubule nucleation	1	1053.2×	0.005	DCTN1
mitotic nuclear membrane disassembly	1	936.2×	0.005	DCTN1
ventral spinal cord development	1	936.2×	0.005	DCTN1
choline transport	1	766.0×	0.005	SLC5A7
maintenance of synapse structure	1	766.0×	0.005	DCTN1
microtubule anchoring at centrosome	1	702.2×	0.005	DCTN1
centriole-centriole cohesion	1	648.1×	0.005	DCTN1
neuron projection maintenance	1	561.7×	0.005	DCTN1
regulation of mitotic spindle organization	1	421.3×	0.006	DCTN1
synaptic transmission, cholinergic	1	401.2×	0.006	SLC5A7
melanosome transport	1	383.0×	0.006	DCTN1
nuclear migration	1	366.4×	0.006	DCTN1
positive regulation of microtubule polymerization	1	337.0×	0.006	DCTN1
neuromuscular synaptic transmission	1	300.9×	0.006	SLC5A7
motor behavior	1	280.9×	0.006	DCTN1
neuromuscular junction development	1	263.3×	0.006	DCTN1
neuromuscular process	1	263.3×	0.006	DCTN1
establishment of mitotic spindle orientation	1	240.7×	0.006	DCTN1
neuron cellular homeostasis	1	227.7×	0.006	DCTN1
neurotransmitter transport	1	210.7×	0.006	SLC5A7
non-motile cilium assembly	1	145.3×	0.009	DCTN1
retrograde transport, endosome to Golgi	1	102.8×	0.012	DCTN1
transmembrane transport	1	84.3×	0.014	SLC5A7
mitotic cell cycle	1	66.9×	0.017	DCTN1
in utero embryonic development	1	36.0×	0.030	SLC5A7
cell division	1	23.1×	0.043	DCTN1
nervous system development	1	23.0×	0.043	DCTN1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
SLC5A7	1	3
DCTN1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CHOLINE CHLORIDE	3	SLC5A7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC5A7	34	Binding:24, Functional:10
DCTN1	1	Binding:1

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

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)
CHOLINE CHLORIDE	3	SLC5A7

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	SLC5A7
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.