Charcot-Marie-Tooth disease type 1C

Summary

Charcot-Marie-Tooth disease type 1C (MONDO:0010995) is a disease caused by LITAF (GenCC Strong), with 3 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: LITAF (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 224
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 1C
Mondo ID	MONDO:0010995
MeSH	C537984
OMIM	601098
Orphanet	101083
DOID	DOID:0110151
ICD-11	1224517226
UMLS	C0270913
MedGen	75728
GARD	0001247
Is cancer (heuristic)	no

Also known as: Charcot Marie Tooth disease type 1C · Charcot-Marie-Tooth disease type 1 caused by mutation in LITAF · Charcot-Marie-Tooth disease, demyelinating, type 1C · Charcot-Marie-Tooth disease, type 1C · CMT 1C · CMT1C · HMSN1C · LITAF Charcot-Marie-Tooth disease type 1

Data availability: 224 ClinVar variants · 3 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 › Charcot-Marie-Tooth disease › Charcot-Marie-Tooth disease type 1 › Charcot-Marie-Tooth disease type 1C

Related subtypes (5): Charcot-Marie-Tooth disease type 1B, Charcot-Marie-Tooth disease type 1A, Charcot-Marie-Tooth disease type 1E, Charcot-Marie-Tooth disease type 1D, Charcot-Marie-Tooth disease type 1F

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

224 retrieved; paginated sample, class counts are floors:

125 uncertain significance, 46 likely benign, 19 benign, 18 conflicting classifications of pathogenicity, 8 benign/likely benign, 5 pathogenic, 2 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
41229	NM_001136472.2(LITAF):c.332C>G (p.Ala111Gly)	LITAF	Pathogenic	criteria provided, multiple submitters, no conflicts
41230	NM_001136472.2(LITAF):c.403C>A (p.Pro135Thr)	LITAF	Pathogenic	criteria provided, single submitter
6057	NM_001136472.2(LITAF):c.334G>A (p.Gly112Ser)	LITAF	Pathogenic	criteria provided, multiple submitters, no conflicts
6058	NM_001136472.2(LITAF):c.344C>A (p.Thr115Asn)	LITAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6059	NM_001136472.2(LITAF):c.346T>G (p.Trp116Gly)	LITAF	Pathogenic	criteria provided, single submitter
6060	NM_001136472.2(LITAF):c.364C>G (p.Leu122Val)	LITAF	Pathogenic	no assertion criteria provided
14029	NM_006158.5(NEFL):c.64C>T (p.Pro22Ser)	NEFL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2502274	NM_001136472.2(LITAF):c.403C>G (p.Pro135Ala)	LITAF	Likely pathogenic	criteria provided, single submitter
1745340	NM_001136472.2(LITAF):c.50C>T (p.Pro17Leu)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215840	NM_001136472.2(LITAF):c.146C>T (p.Thr49Met)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
245638	NM_001136472.2(LITAF):c.478C>T (p.Arg160Cys)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
317784	NM_001136472.2(LITAF):c.159G>A (p.Gly53=)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
317789	NM_001136472.2(LITAF):c.44C>T (p.Ser15Leu)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
404113	NM_001136472.2(LITAF):c.151C>T (p.Pro51Ser)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
404114	NM_001136472.2(LITAF):c.302A>G (p.Lys101Arg)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464048	NM_001136472.2(LITAF):c.226G>A (p.Val76Met)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
572892	NM_001136472.2(LITAF):c.25G>A (p.Ala9Thr)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
637892	NM_001136472.2(LITAF):c.477G>A (p.Lys159=)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
639258	NM_001136472.2(LITAF):c.331G>A (p.Ala111Thr)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
640744	NM_001136472.2(LITAF):c.412G>A (p.Val138Met)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
641266	NM_001136472.2(LITAF):c.268C>T (p.Arg90Cys)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
648776	NM_001136472.2(LITAF):c.310G>A (p.Val104Met)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
872382	NM_001136472.2(LITAF):c.378-7C>T	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
944155	NM_001136472.2(LITAF):c.55G>A (p.Ala19Thr)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
944854	NM_001136472.2(LITAF):c.157G>A (p.Gly53Arg)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
945669	NM_001136472.2(LITAF):c.26C>T (p.Ala9Val)	LITAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1480512	NC_000016.9:g.(?8829597)(11650586_?)dup	ABAT	Uncertain significance	criteria provided, single submitter
1024595	NC_000016.9:g.(?11650347)(11650606_?)del	LITAF	Uncertain significance	criteria provided, single submitter
1025234	NM_001136472.2(LITAF):c.283T>C (p.Cys95Arg)	LITAF	Uncertain significance	criteria provided, single submitter
1034788	NM_001136472.2(LITAF):c.168del (p.Met56fs)	LITAF	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
LITAF	Strong	Autosomal dominant	Charcot-Marie-Tooth disease type 1C	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LITAF	Orphanet:101083	Charcot-Marie-Tooth disease type 1C
ABAT	Orphanet:2066	Gamma-aminobutyric acid transaminase deficiency
NEFL	Orphanet:101085	Charcot-Marie-Tooth disease type 1F
NEFL	Orphanet:228374	Charcot-Marie-Tooth disease type 2B5
NEFL	Orphanet:99939	Autosomal dominant Charcot-Marie-Tooth disease type 2E

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
LITAF	HGNC:16841	ENSG00000189067	Q99732	Lipopolysaccharide-induced tumor necrosis factor-alpha factor	gencc,clinvar
ABAT	HGNC:23	ENSG00000183044	P80404	4-aminobutyrate aminotransferase, mitochondrial	clinvar
NEFL	HGNC:7739	ENSG00000277586	P07196	Neurofilament light polypeptide	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LITAF	Lipopolysaccharide-induced tumor necrosis factor-alpha factor	Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation.
ABAT	4-aminobutyrate aminotransferase, mitochondrial	Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively.
NEFL	Neurofilament light polypeptide	Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · 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
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LITAF	Other/Unknown	no		LITAF, LITAF_fam
ABAT	Enzyme (other)	yes	2.6.1.19	4NH2But_aminotransferase_euk, Aminotrans_3, PyrdxlP-dep_Trfase_major
NEFL	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom

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
blood	1
palpebral conjunctiva	1
periodontal ligament	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1
dorsal root ganglion	1
lateral nuclear group of thalamus	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LITAF	294	ubiquitous	marker	blood, palpebral conjunctiva, periodontal ligament
ABAT	289	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus
NEFL	214	broad	marker	dorsal root ganglion, pons, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEFL	4,644
LITAF	1,814
ABAT	1,711

Structural data

PDB: 0 · AlphaFold-only: 3 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABAT	P80404	93.91
NEFL	P07196	73.66
LITAF	Q99732	70.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Degradation of GABA	1	2855.0×	0.002	ABAT
Ras activation upon Ca2+ influx through NMDA receptor	1	285.5×	0.006	NEFL
Unblocking of NMDA receptors, glutamate binding and activation	1	271.9×	0.006	NEFL
Negative regulation of NMDA receptor-mediated neuronal transmission	1	271.9×	0.006	NEFL
Long-term potentiation	1	237.9×	0.006	NEFL
Assembly and cell surface presentation of NMDA receptors	1	126.9×	0.009	NEFL
RAF/MAP kinase cascade	1	30.5×	0.032	NEFL

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
intermediate filament polymerization or depolymerization	1	5617.3×	0.002	NEFL
copulation	1	2808.7×	0.002	ABAT
obsolete GABA metabolic process	1	2808.7×	0.002	ABAT
GABA catabolic process	1	2808.7×	0.002	ABAT
regulation of macrophage cytokine production	1	2808.7×	0.002	LITAF
negative regulation of gamma-aminobutyric acid secretion	1	2808.7×	0.002	ABAT
positive regulation of prolactin secretion	1	2808.7×	0.002	ABAT
response to sodium arsenite	1	2808.7×	0.002	NEFL
response to acrylamide	1	2808.7×	0.002	NEFL
positive regulation of aspartate secretion	1	2808.7×	0.002	ABAT
neurofilament bundle assembly	1	1872.4×	0.003	NEFL
negative regulation of dopamine secretion	1	1404.3×	0.003	ABAT
positive regulation of dopamine metabolic process	1	1404.3×	0.003	ABAT
regulation of axon diameter	1	1123.5×	0.003	NEFL
positive regulation of heat generation	1	1123.5×	0.003	ABAT
positive regulation of inhibitory postsynaptic potential	1	936.2×	0.004	ABAT
GABA biosynthetic process	1	702.2×	0.004	ABAT
peripheral nervous system axon regeneration	1	702.2×	0.004	NEFL
positive regulation of uterine smooth muscle contraction	1	702.2×	0.004	ABAT
neurofilament cytoskeleton organization	1	561.7×	0.005	NEFL
retrograde axonal transport	1	510.7×	0.005	NEFL
locomotion	1	510.7×	0.005	NEFL
negative regulation of motor neuron apoptotic process	1	510.7×	0.005	NEFL
axonal transport of mitochondrion	1	468.1×	0.005	NEFL
nervous system process	1	401.2×	0.006	ABAT
response to corticosterone	1	374.5×	0.006	NEFL
motor neuron apoptotic process	1	374.5×	0.006	NEFL
protein polymerization	1	330.4×	0.006	NEFL
response to iron ion	1	312.1×	0.006	ABAT
regulation of synapse maturation	1	312.1×	0.006	NEFL

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LITAF	0	0
ABAT	0	0
NEFL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ABAT	41	Binding:41
LITAF	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABAT	2.6.1.19	4-aminobutyrate-2-oxoglutarate transaminase

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

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	1	ABAT
E	Difficult family or no structure, no drug	2	LITAF, NEFL

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LITAF	1	—
ABAT	41	—
NEFL	0	—

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
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease