Progressive bulbar palsy of childhood

Summary

Progressive bulbar palsy of childhood (MONDO:0100428) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	progressive bulbar palsy of childhood
Mondo ID	MONDO:0100428
OMIM	211500
Orphanet	56965
DOID	DOID:0080632
SNOMED CT	230246005
UMLS	C0393540
MedGen	140728
GARD	0026209
Is cancer (heuristic)	no

Also known as: Fazio-Londe disease

Data availability: 25 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › cranial nerve neuropathy › cranial nerve palsy › progressive bulbar palsy › progressive bulbar palsy of childhood

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

25 retrieved; paginated sample, class counts are floors:

13 benign, 3 conflicting classifications of pathogenicity, 3 pathogenic, 3 uncertain significance, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
210018	NM_033409.4(SLC52A3):c.639C>G (p.Tyr213Ter)	SLC52A3	Pathogenic	criteria provided, multiple submitters, no conflicts
210021	NM_033409.4(SLC52A3):c.935C>T (p.Ala312Val)	SLC52A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210025	NM_033409.4(SLC52A3):c.1198-2A>C	SLC52A3	Pathogenic	no assertion criteria provided
800969	NM_033409.4(SLC52A3):c.71G>A (p.Trp24Ter)	SLC52A3	Pathogenic	criteria provided, single submitter
143	NM_033409.4(SLC52A3):c.106G>A (p.Glu36Lys)	SLC52A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1686212	NM_033409.4(SLC52A3):c.446G>A (p.Gly149Asp)	SLC52A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
579662	NM_033409.4(SLC52A3):c.787C>T (p.His263Tyr)	SLC52A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210029	NM_033409.4(SLC52A3):c.1371C>G (p.Phe457Leu)	SLC52A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
570161	NM_033409.4(SLC52A3):c.890C>T (p.Pro297Leu)	SLC52A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
856021	NM_033409.4(SLC52A3):c.58A>C (p.Ile20Leu)	SLC52A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892489	NC_000001.11:g.809289_809290insATCAGGTCA	LINC01409	Benign	criteria provided, single submitter
1185470	NM_033409.4(SLC52A3):c.1197+108C>T	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
1185471	NM_033409.4(SLC52A3):c.1197+106A>G	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
1185472	NM_033409.4(SLC52A3):c.1073+92T>C	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
1185522	NM_033409.4(SLC52A3):c.568-200T>C	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262228	NM_033409.4(SLC52A3):c.-14_-6del	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262230	NM_033409.4(SLC52A3):c.1233T>C (p.Ser411=)	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262232	NM_033409.4(SLC52A3):c.240C>T (p.Gly80=)	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262233	NM_033409.4(SLC52A3):c.321C>T (p.Ala107=)	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262236	NM_033409.4(SLC52A3):c.600C>T (p.Pro200=)	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262238	NM_033409.4(SLC52A3):c.765C>T (p.Leu255=)	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262240	NM_033409.4(SLC52A3):c.833C>T (p.Thr278Met)	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262241	NM_033409.4(SLC52A3):c.907A>G (p.Ile303Val)	SLC52A3	Benign	criteria provided, multiple submitters, no conflicts
262242	NM_033409.4(SLC52A3):c.9C>T (p.Phe3=)	SLC52A3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
476615	NM_033409.4(SLC52A3):c.834G>A (p.Thr278=)	SLC52A3	Likely benign	criteria provided, multiple submitters, no conflicts

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

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC52A3	HGNC:16187	ENSG00000101276	Q9NQ40	Solute carrier family 52, riboflavin transporter, member 3	clinvar
LINC01409	HGNC:50701	ENSG00000237491		long intergenic non-protein coding RNA 1409	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: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC52A3	Other/Unknown	no		Riboflavin_transptr
LINC01409	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
mucosa of transverse colon	1
right testis	1
calcaneal tendon	1
right coronary artery	1
sural nerve	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
LINC01409	172		yes	sural nerve, calcaneal tendon, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC52A3	864
LINC01409	0

Structural data

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

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 2 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: 2

Druggability breadth: 0 of 2 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
LINC01409	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	2	SLC52A3, LINC01409

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC52A3	0	—
LINC01409	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.