neuropathy, hereditary motor and sensory, type VIc, with optic atrophy
diseaseOn this page
Also known as Charcot-Marie-Tooth Disease, Type 6CCMT 6CCMT6CHMSN 6CHMSN6C
Summary
neuropathy, hereditary motor and sensory, type VIc, with optic atrophy (MONDO:0032792) is a disease caused by PDXK (GenCC Strong), with 1 cohort gene and 1 clinical trial.
At a glance
- Causal gene: PDXK (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 9
- Clinical trials: 1
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | neuropathy, hereditary motor and sensory, type VIc, with optic atrophy |
| Mondo ID | MONDO:0032792 |
| OMIM | 618511 |
| UMLS | C5193137 |
| MedGen | 1680245 |
| GARD | 0025745 |
| Is cancer (heuristic) | no |
Also known as: Charcot-Marie-Tooth Disease, Type 6C · CMT 6C · CMT6C · HMSN 6C · HMSN6C · neuropathy, hereditary motor and sensory, type VIc, with optic atrophy
Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.
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 › hereditary motor and sensory neuropathy › hereditary motor and sensory neuropathy type 6 › neuropathy, hereditary motor and sensory, type VIc, with optic atrophy
Related subtypes (2): neuropathy, hereditary motor and sensory, type 6A, neuropathy, hereditary motor and sensory, type 6B
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
9 retrieved; paginated sample, class counts are floors:
3 benign, 2 uncertain significance, 2 pathogenic, 1 likely benign, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 636264 | NM_003681.5(PDXK):c.682G>A (p.Ala228Thr) | PDXK | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 636265 | NM_003681.5(PDXK):c.659G>A (p.Arg220Gln) | PDXK | Pathogenic | no assertion criteria provided |
| 812519 | NM_003681.5(PDXK):c.225T>A (p.Asn75Lys) | PDXK | Likely pathogenic | criteria provided, single submitter |
| 2348515 | NM_003681.5(PDXK):c.842G>A (p.Gly281Glu) | PDXK | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2434643 | NM_003681.5(PDXK):c.509G>A (p.Arg170Gln) | PDXK | Uncertain significance | criteria provided, single submitter |
| 1013193 | NM_003681.5(PDXK):c.374C>T (p.Ser125Leu) | PDXK | Likely benign | criteria provided, multiple submitters, no conflicts |
| 1267789 | NM_003681.5(PDXK):c.*14T>C | PDXK | Benign | criteria provided, multiple submitters, no conflicts |
| 1268466 | NM_003681.5(PDXK):c.387G>A (p.Pro129=) | PDXK | Benign | criteria provided, multiple submitters, no conflicts |
| 1327004 | NM_003681.5(PDXK):c.331+26T>G | PDXK | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 2 · Orphanet: 0 · 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 |
|---|---|---|---|---|
| PDXK | Strong | Autosomal recessive | neuropathy, hereditary motor and sensory, type VIc, with optic atrophy | 2 |
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 |
|---|---|---|---|---|---|
| PDXK | HGNC:8819 | ENSG00000160209 | O00764 | Pyridoxal kinase | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PDXK | Pyridoxal kinase | Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5’-phosphate (PLP), pyridoxine 5’-phosphate (PNP) and pyridoxamine 5’-phosphate (PMP), respectively. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
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 |
|---|---|---|---|
| Kinase | 1 | 27.7× | 0.036 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PDXK | Kinase | yes | 2.7.1.35 | PyrdxlKinase, PM/HMP-P_kinase-1, Ribokinase-like |
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 |
|---|---|
| adult organism | 1 |
| left testis | 1 |
| right testis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PDXK | 295 | ubiquitous | marker | left testis, right testis, adult organism |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PDXK | 1,899 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PDXK | O00764 | 10 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. 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 |
|---|---|---|---|---|
| Vitamin B6 activation to pyridoxal phosphate | 1 | 3806.7× | 5e-04 | PDXK |
| Neutrophil degranulation | 1 | 23.1× | 0.043 | PDXK |
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 |
|---|---|---|---|---|
| pyridoxal 5’-phosphate salvage | 1 | 16852.0× | 9e-05 | PDXK |
| pyridoxal metabolic process | 1 | 16852.0× | 9e-05 | PDXK |
| pyridoxamine metabolic process | 1 | 8426.0× | 1e-04 | PDXK |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · 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).
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 |
|---|---|
| PDXK | SUNITINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PDXK | 6 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| SUNITINIB | 4 | PDXK |
| VOLASERTIB | 3 | PDXK |
| LUCITANIB | 2 | PDXK |
| TG100-115 | 2 | PDXK |
| FGFR INHIBITOR DEBIO 1347 | 2 | PDXK |
| BI-2536 | 2 | PDXK |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PDXK | 21 | Binding:20, ADMET:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PDXK | 2.7.1.35 | pyridoxal kinase |
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
6 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) |
|---|---|---|
| SUNITINIB | 4 | PDXK |
| VOLASERTIB | 3 | PDXK |
| LUCITANIB | 2 | PDXK |
| TG100-115 | 2 | PDXK |
| FGFR INHIBITOR DEBIO 1347 | 2 | PDXK |
| BI-2536 | 2 | PDXK |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | PDXK |
| 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 | 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: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05687474 | Not specified | COMPLETED | Baby Detect : Genomic Newborn Screening |
Related Atlas pages
- Cohort genes: PDXK