Madras motor neuron disease

Summary

Madras motor neuron disease (MONDO:0015307) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		200	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0001283	Bulbar palsy	Very frequent (80-99%)
HP:0001621	Weak voice	Frequent (30-79%)
HP:0002460	Distal muscle weakness	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0003693	Distal amyotrophy	Frequent (30-79%)
HP:0006801	Hyperactive deep tendon reflexes	Frequent (30-79%)
HP:0007289	Limb fasciculations	Frequent (30-79%)
HP:0000360	Tinnitus	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0001315	Reduced tendon reflexes	Occasional (5-29%)
HP:0001317	Abnormal cerebellum morphology	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0100753	Schizophrenia	Occasional (5-29%)
HP:0007663	Reduced visual acuity	Very rare (<1-4%)
HP:0010628	Facial palsy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Madras motor neuron disease
Mondo ID	MONDO:0015307
Orphanet	137867
ICD-11	1764644031
UMLS	C0393551
MedGen	581442
GARD	0019887
Is cancer (heuristic)	no

Also known as: MMND

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › motor neuron disorder › Madras motor neuron disease

Related subtypes (3): amyotrophic lateral sclerosis, acquired motor neuron disease, hereditary motor neuron disease

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 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
873320	NM_033409.4(SLC52A3):c.802C>T (p.Arg268Trp)	SLC52A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC52A3	Orphanet:572550	RFVT3-related riboflavin transporter deficiency

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
SLC52A3	HGNC:16187	ENSG00000101276	Q9NQ40	Solute carrier family 52, riboflavin transporter, member 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC52A3	Solute carrier family 52, riboflavin transporter, member 3	Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism.

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)
SLC52A3	Other/Unknown	no		Riboflavin_transptr

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
left testis	1
mucosa of transverse colon	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC52A3	169	broad	marker	right testis, mucosa of transverse colon, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC52A3	864

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC52A3	Q9NQ40	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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 B2 (riboflavin) metabolism	1	1631.4×	0.002	SLC52A3
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.011	SLC52A3
Metabolism of vitamins and cofactors	1	116.5×	0.011	SLC52A3
Metabolism	1	11.6×	0.086	SLC52A3

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
flavin adenine dinucleotide biosynthetic process	1	8426.0×	5e-04	SLC52A3
riboflavin transport	1	4213.0×	5e-04	SLC52A3
riboflavin metabolic process	1	3370.4×	5e-04	SLC52A3
cellular response to heat	1	343.9×	0.004	SLC52A3
sensory perception of sound	1	100.9×	0.010	SLC52A3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC52A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SLC52A3

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)
SLC52A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.