MME-related autosomal dominant Charcot Marie Tooth disease type 2

Summary

MME-related autosomal dominant Charcot Marie Tooth disease type 2 (MONDO:0044657) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		19	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	MME-related autosomal dominant Charcot Marie Tooth disease type 2
Mondo ID	MONDO:0044657
Orphanet	497757
UMLS	C5567450
MedGen	1798873
GARD	0017916
Is cancer (heuristic)	no

Also known as: MME-related autosomal dominant CMT2 · MME-related autosomal dominant hereditary motor and sensory neuropathy type 2

Data availability: 3 ClinVar variants · 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 › MME-related autosomal dominant Charcot Marie Tooth disease type 2

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 KIF5A mutation, 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, 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

3 retrieved; paginated sample, class counts are floors:

3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1486041	NM_007289.4(MME):c.1520A>G (p.Tyr507Cys)	MME	Uncertain significance	criteria provided, multiple submitters, no conflicts
1676248	NM_007289.4(MME):c.193T>C (p.Ser65Pro)	MME	Uncertain significance	criteria provided, multiple submitters, no conflicts
931880	NM_007289.4(MME):c.1735G>A (p.Gly579Ser)	MME	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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
MME	Definitive	Semidominant	Charcot-Marie-Tooth disease axonal type 2T	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MME	Orphanet:495274	Charcot-Marie-Tooth disease type 2T
MME	Orphanet:497757	MME-related autosomal dominant Charcot Marie Tooth disease type 2
MME	Orphanet:497764	Spinocerebellar ataxia type 43
MME	Orphanet:69063	Congenital membranous nephropathy due to fetomaternal anti-neutral endopeptidase alloimmunization

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
MME	HGNC:7154	ENSG00000196549	P08473	Neprilysin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MME	Neprilysin	Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MME	Protease	yes	3.4.24.11	Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C

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
jejunal mucosa	1
metanephric glomerulus	1
renal glomerulus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MME	212	ubiquitous	marker	jejunal mucosa, renal glomerulus, metanephric glomerulus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MME	2,648

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MME	P08473	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Physiological factors	1	671.8×	0.006	MME
Metabolism of Angiotensinogen to Angiotensins	1	634.4×	0.006	MME
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	543.8×	0.006	MME
Peptide hormone metabolism	1	271.9×	0.009	MME
Cardiac conduction	1	108.8×	0.018	MME
Muscle contraction	1	77.2×	0.022	MME
Innate Immune System	1	25.5×	0.054	MME
Neutrophil degranulation	1	23.1×	0.054	MME
Immune System	1	13.0×	0.081	MME
Metabolism of proteins	1	12.4×	0.081	MME

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
neuropeptide processing	1	16852.0×	0.002	MME
creatinine metabolic process	1	8426.0×	0.002	MME
substance P catabolic process	1	5617.3×	0.002	MME
amygdala development	1	2808.7×	0.002	MME
hormone catabolic process	1	2808.7×	0.002	MME
bradykinin catabolic process	1	2407.4×	0.002	MME
amyloid-beta clearance by cellular catabolic process	1	2106.5×	0.002	MME
amyloid-beta metabolic process	1	1532.0×	0.002	MME
cellular response to UV-A	1	1404.3×	0.002	MME
cellular response to UV-B	1	1404.3×	0.002	MME
angiotensin maturation	1	1296.3×	0.002	MME
peptide metabolic process	1	1203.7×	0.002	MME
replicative senescence	1	991.3×	0.002	MME
amyloid-beta clearance	1	936.2×	0.002	MME
positive regulation of long-term synaptic potentiation	1	674.1×	0.003	MME
positive regulation of neurogenesis	1	581.1×	0.003	MME
cellular response to cytokine stimulus	1	543.6×	0.003	MME
placenta development	1	443.5×	0.004	MME
sensory perception of pain	1	374.5×	0.004	MME
response to estrogen	1	343.9×	0.004	MME
learning or memory	1	240.7×	0.005	MME
protein catabolic process	1	237.3×	0.005	MME
hippocampus development	1	230.8×	0.005	MME
lung development	1	198.3×	0.006	MME
memory	1	183.2×	0.006	MME
protein processing	1	170.2×	0.007	MME
kidney development	1	140.4×	0.008	MME
multicellular organism growth	1	137.0×	0.008	MME
proteolysis	1	34.2×	0.029	MME

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MME	4	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CYCLOVALONE	2	MME
OMAPATRILAT	2	MME
SAMPATRILAT	2	MME
CANDOXATRILAT	2	MME

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MME	125	Binding:110, ADMET:15

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MME	3.4.24.11	neprilysin

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MME	125

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

4 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)
CYCLOVALONE	2	MME
OMAPATRILAT	2	MME
SAMPATRILAT	2	MME
CANDOXATRILAT	2	MME

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	MME
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: 0.