Motor peripheral neuropathy

Summary

Motor peripheral neuropathy (MONDO:0002316) is a disease (an umbrella term covering 9 Mondo subtypes) with 3 cohort genes and 3 clinical trials. Top therapeutic interventions include ascorbic acid.

At a glance

• Umbrella term: 9 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 3
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	motor peripheral neuropathy
Mondo ID	MONDO:0002316
DOID	DOID:2477
NCIT	C3500
SNOMED CT	95663000
UMLS	C0271683
MedGen	82885
Is cancer (heuristic)	no

Also known as: hereditary motor and sensory neuropathy · HSMN · HSMN - hereditary sensory and motor neuropathy · peripheral motor neuropathy

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › motor peripheral neuropathy

Related subtypes (29): autoimmune neuropathy, autonomic neuropathy, mononeuropathy, ischemic neuropathy, polyneuropathy, neuritis, sensory peripheral neuropathy, uremic neuropathy, nerve compression syndrome, axonal neuropathy, diabetic neuropathy, acquired peripheral neuropathy, hereditary peripheral neuropathy, neuralgia, peripheral nerve lesion, nerve plexus disorder, traumatic neuropathy, radiation-induced neuropathy, vasculitic neuropathy, chronic idiopathic neuropathy, chemotherapy-induced neuropathy, infectious neuropathy, vitamin deficiency related neuropathy, paraproteinemia-associated neuropathy, neuropathy in cryoglobulinemia, neuropathy in endocrine disorder, sarcoid neuropathy, neuropathy, small fiber, idiopathic small fibers neuropathy

Subtypes (9): motor nerve neuritis, glossopharyngeal motor neuropathy, Charcot-Marie-Tooth disease type 5, neuropathy, hereditary motor and sensory, type 6A, hereditary motor and sensory neuropathy, Okinawa type, Charcot-Marie-Tooth disease type 4G, Charcot-Marie-Tooth disease axonal type 2C, neuropathy, hereditary motor and sensory, type 6B, peripheral motor neuropathy, childhood-onset, biotin-responsive

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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
599379	NM_001330701.2(AGTPBP1):c.2186+2T>G	AGTPBP1	Likely pathogenic	no assertion criteria provided
523532	NM_022489.4(INF2):c.3247A>G (p.Ser1083Gly)	INF2	Uncertain significance	criteria provided, single submitter
374064	NM_001145809.2(MYH14):c.1945+6G>A	MYH14	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AGTPBP1	Orphanet:2254	Pontocerebellar hypoplasia type 1
MYH14	Orphanet:397744	MYH14-related peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
MYH14	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
INF2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
INF2	Orphanet:93114	Autosomal dominant intermediate Charcot-Marie-Tooth disease type E

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AGTPBP1	HGNC:17258	ENSG00000135049	Q9UPW5	Cytosolic carboxypeptidase 1	clinvar
MYH14	HGNC:23212	ENSG00000105357	Q7Z406	Myosin-14	clinvar
INF2	HGNC:23791	ENSG00000203485	Q27J81	Inverted formin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AGTPBP1	Cytosolic carboxypeptidase 1	Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins.
MYH14	Myosin-14	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
INF2	Inverted formin-2	Severs actin filaments and accelerates their polymerization and depolymerization.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Protease	1	12.2×	0.239
Scaffold/PPI	1	5.8×	0.246
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AGTPBP1	Protease	yes	3.4.17.24	Peptidase_M14, ARM-like, ARM-type_fold
MYH14	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
INF2	Other/Unknown	no		WH2_dom, FH3_dom, GTPase-bd

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	1
cortical plate	1
monocyte	1
gastrocnemius	1
ileal mucosa	1
mucosa of transverse colon	1
nerve	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AGTPBP1	280	ubiquitous	marker	cortical plate, corpus callosum, monocyte
MYH14	227	broad	marker	mucosa of transverse colon, ileal mucosa, gastrocnemius
INF2	260	ubiquitous	marker	sural nerve, nerve, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INF2	2,070
MYH14	1,569
AGTPBP1	815

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INF2	Q27J81	10
MYH14	Q7Z406	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGTPBP1	Q9UPW5	75.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 3 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
Sema4D in semaphorin signaling	1	335.9×	0.014	MYH14
RHO GTPases activate CIT	1	300.5×	0.014	MYH14
RHO GTPases Activate ROCKs	1	300.5×	0.014	MYH14
Sema4D induced cell migration and growth-cone collapse	1	285.5×	0.014	MYH14
RHO GTPases activate PAKs	1	271.9×	0.014	MYH14
Semaphorin interactions	1	196.9×	0.014	MYH14
EPHA-mediated growth cone collapse	1	190.3×	0.014	MYH14
RHO GTPases activate PKNs	1	158.6×	0.015	MYH14
Carboxyterminal post-translational modifications of tubulin	1	119.0×	0.018	AGTPBP1
EPH-Ephrin signaling	1	82.8×	0.023	MYH14
RHO GTPase Effectors	1	34.0×	0.050	MYH14
Axon guidance	1	22.6×	0.067	MYH14
Nervous system development	1	21.5×	0.067	MYH14
Signaling by Rho GTPases	1	17.1×	0.075	MYH14
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.075	MYH14
Post-translational protein modification	1	9.6×	0.121	AGTPBP1
Developmental Biology	1	7.2×	0.149	MYH14
Metabolism of proteins	1	6.2×	0.164	AGTPBP1
Signal Transduction	1	5.1×	0.187	MYH14

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
anterograde axonal transport of mitochondrion	1	2808.7×	0.003	AGTPBP1
protein deglutamylation	1	1872.4×	0.003	AGTPBP1
retrograde axonal transport of mitochondrion	1	1872.4×	0.003	AGTPBP1
eye photoreceptor cell differentiation	1	1404.3×	0.003	AGTPBP1
C-terminal protein deglutamylation	1	1404.3×	0.003	AGTPBP1
mitochondrion organization	2	101.2×	0.003	AGTPBP1, MYH14
protein side chain deglutamylation	1	936.2×	0.004	AGTPBP1
regulation of mitochondrial fission	1	702.2×	0.005	INF2
cerebellar Purkinje cell differentiation	1	351.1×	0.008	AGTPBP1
vocalization behavior	1	295.6×	0.008	MYH14
central nervous system neuron development	1	267.5×	0.008	AGTPBP1
actin filament-based movement	1	267.5×	0.008	MYH14
olfactory bulb development	1	255.3×	0.008	AGTPBP1
actomyosin structure organization	1	187.2×	0.008	MYH14
positive regulation of ubiquitin-dependent protein catabolic process	1	187.2×	0.008	AGTPBP1
neuromuscular process	1	175.5×	0.008	AGTPBP1
skeletal muscle contraction	1	170.2×	0.008	MYH14
adult walking behavior	1	165.2×	0.008	AGTPBP1
neuronal action potential	1	160.5×	0.008	MYH14
actin filament polymerization	1	160.5×	0.008	INF2
skeletal muscle tissue development	1	96.8×	0.013	MYH14
mitotic cytokinesis	1	86.4×	0.014	MYH14
retina development in camera-type eye	1	85.1×	0.014	AGTPBP1
regulation of cell shape	1	41.0×	0.027	MYH14
sensory perception of sound	1	33.6×	0.032	MYH14
negative regulation of cell population proliferation	1	14.0×	0.072	AGTPBP1
proteolysis	1	11.4×	0.085	AGTPBP1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 3 of 3 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
MYH14	TUCATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYH14	1	4
AGTPBP1	0	0
INF2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TUCATINIB	4	MYH14

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
AGTPBP1	1	Binding:1
MYH14	1	Binding:1
INF2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AGTPBP1	3.4.17.24	tubulin-glutamate carboxypeptidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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)
TUCATINIB	4	MYH14

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MYH14
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	AGTPBP1
E	Difficult family or no structure, no drug	1	INF2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AGTPBP1	1	—
INF2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00271635	PHASE2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT07072676	Not specified	ENROLLING_BY_INVITATION	The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASCORBIC ACID	4	1