autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation

Summary

autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation (MONDO:0017940) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation
Mondo ID	MONDO:0017940
Orphanet	324611
SNOMED CT	764730007
UMLS	C4707173
MedGen	1633598
GARD	0021447
Is cancer (heuristic)	no

Also known as: CMT2 due to KIF5A mutation

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

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › hereditary peripheral neuropathy › Charcot-Marie-Tooth disease › Charcot-Marie-Tooth disease type 2 › autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation

Related subtypes (37): Charcot-Marie-Tooth disease type 2A1, Charcot-Marie-Tooth disease type 2B, Charcot-Marie-Tooth disease type 2D, Charcot-Marie-Tooth disease type 2B1, Charcot-Marie-Tooth disease type 2B2, Charcot-Marie-Tooth disease axonal type 2C, Charcot-Marie-Tooth disease axonal type 2F, Charcot-Marie-Tooth disease type 2I, Charcot-Marie-Tooth disease type 2E, Charcot-Marie-Tooth disease axonal type 2H, Charcot-Marie-Tooth disease type 2J, Charcot-Marie-Tooth disease axonal type 2K, Charcot-Marie-Tooth disease axonal type 2L, Charcot-Marie-Tooth disease type 2A2, giant axonal neuropathy 2, Charcot-Marie-Tooth disease axonal type 2N, Charcot-Marie-Tooth disease axonal type 2O, Charcot-Marie-Tooth disease axonal type 2P, Charcot-Marie-Tooth disease axonal type 2Q, Charcot-Marie-Tooth disease type 2R, Charcot-Marie-Tooth disease axonal type 2S, Charcot-Marie-Tooth disease axonal type 2U, Charcot-Marie-Tooth disease axonal type 2V, autosomal dominant Charcot-Marie-Tooth disease type 2W, Charcot-Marie-Tooth disease axonal type 2X, Charcot-Marie-Tooth disease type 2Y, Charcot-Marie-Tooth disease axonal type 2Z, Charcot-Marie-Tooth disease axonal type 2CC, autosomal dominant Charcot-Marie-Tooth disease type 2M, Charcot-Marie-Tooth disease type 2B5, autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation, autosomal dominant Charcot-Marie-Tooth disease type 2K, Charcot-Marie-Tooth disease, axonal, type 2EE, autosomal dominant charcot-marie-tooth disease type 2 due to DGAT2 mutation, Charcot-Marie-Tooth disease type 2T, MME-related autosomal dominant Charcot Marie Tooth disease type 2, Charcot-Marie-tooth disease, axonal, type 2DD

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

1 retrieved; paginated sample, class counts are floors:

1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1501315	NM_004984.4(KIF5A):c.996A>G (p.Ser332=)	KIF5A	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 2 · 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
KIF5A	Supportive	Autosomal dominant	autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIF5A	Orphanet:100991	Autosomal dominant spastic paraplegia type 10
KIF5A	Orphanet:324611	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation

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
KIF5A	HGNC:6323	ENSG00000155980	Q12840	Kinesin heavy chain isoform 5A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF5A	Kinesin heavy chain isoform 5A	Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL).

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)
KIF5A	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase

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 hemisphere	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF5A	198	broad	marker	right frontal lobe, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF5A	3,241

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF5A	Q12840	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
RHO GTPases activate KTN1	1	1038.2×	0.018	KIF5A
Insulin processing	1	456.8×	0.021	KIF5A
Peptide hormone metabolism	1	271.9×	0.023	KIF5A
Kinesins	1	178.4×	0.026	KIF5A
Golgi-to-ER retrograde transport	1	132.8×	0.026	KIF5A
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.026	KIF5A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.026	KIF5A
MHC class II antigen presentation	1	89.2×	0.027	KIF5A
RHO GTPase Effectors	1	68.0×	0.029	KIF5A
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.029	KIF5A
Membrane Trafficking	1	37.1×	0.038	KIF5A
Hemostasis	1	36.0×	0.038	KIF5A
Vesicle-mediated transport	1	34.8×	0.038	KIF5A
Signaling by Rho GTPases	1	34.2×	0.038	KIF5A
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.038	KIF5A
Adaptive Immune System	1	29.8×	0.040	KIF5A
Immune System	1	13.0×	0.085	KIF5A
Metabolism of proteins	1	12.4×	0.085	KIF5A
Signal Transduction	1	10.2×	0.098	KIF5A

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
retrograde neuronal dense core vesicle transport	1	3370.4×	0.001	KIF5A
anterograde dendritic transport of neurotransmitter receptor complex	1	2407.4×	0.001	KIF5A
anterograde axonal protein transport	1	2106.5×	0.001	KIF5A
synaptic vesicle transport	1	842.6×	0.002	KIF5A
microtubule-based movement	1	295.6×	0.005	KIF5A
vesicle-mediated transport	1	96.3×	0.013	KIF5A
axon guidance	1	90.6×	0.013	KIF5A
chemical synaptic transmission	1	77.3×	0.013	KIF5A

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
KIF5A	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
KIF5A	8	Binding:8

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	KIF5A

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)
KIF5A	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.