Brown-Vialetto-van Laere syndrome 1

Summary

Brown-Vialetto-van Laere syndrome 1 (MONDO:0024537) is a disease caused by SLC52A3 (GenCC Definitive), with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC52A3 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 426

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

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

Identifiers

Disease identifiers

Field	Value
Canonical name	Brown-Vialetto-van Laere syndrome 1
Mondo ID	MONDO:0024537
OMIM	211530
Orphanet	572543
DOID	DOID:0080785
NCIT	C133724
UMLS	C0796274
MedGen	163239
GARD	0018010
Is cancer (heuristic)	no

Also known as: Brown-Vialetto-Van Laere syndrome 1 · Brown-Vialetto-van Laere syndrome 1 · Brown-Vialetto-van Laere syndrome caused by mutation in SLC52A3 · BVVLS1 · rfvt2-related riboflavin transporter deficiency · Riboflavin transporter deficiency 2 · RTD2 · SLC52A3 Brown-Vialetto-van Laere syndrome

Data availability: 426 ClinVar variants · 5 GenCC gene-disease records · 3 cell lines.

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 › hereditary motor neuron disease › riboflavin transporter deficiency › Brown-Vialetto-van Laere syndrome 1

Related subtypes (2): progressive bulbar palsy, Brown-Vialetto-van Laere syndrome 2

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

426 retrieved; paginated sample, class counts are floors:

186 uncertain significance, 161 likely benign, 21 pathogenic, 18 benign, 16 conflicting classifications of pathogenicity, 11 benign/likely benign, 6 likely pathogenic, 5 not provided, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1373812	NC_000020.10:g.(?389402)(746418_?)del	SCRT2	Pathogenic	criteria provided, single submitter
188051	NM_001363118.2(SLC52A2):c.808C>T (p.Gln270Ter)	SLC52A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1070902	NM_033409.4(SLC52A3):c.550G>T (p.Glu184Ter)	SLC52A3	Pathogenic	criteria provided, multiple submitters, no conflicts
1074049	NM_033409.4(SLC52A3):c.85del (p.Leu29fs)	SLC52A3	Pathogenic	criteria provided, single submitter
140	NM_033409.4(SLC52A3):c.211G>T (p.Glu71Ter)	SLC52A3	Pathogenic	no assertion criteria provided
142	NM_033409.4(SLC52A3):c.670T>C (p.Phe224Leu)	SLC52A3	Pathogenic	no assertion criteria provided
1425010	NM_033409.4(SLC52A3):c.481_484dup (p.Gly162fs)	SLC52A3	Pathogenic	criteria provided, single submitter
145	NM_033409.4(SLC52A3):c.82C>A (p.Pro28Thr)	SLC52A3	Pathogenic	no assertion criteria provided
1760485	NM_033409.4(SLC52A3):c.775C>T (p.Gln259Ter)	SLC52A3	Pathogenic	criteria provided, multiple submitters, no conflicts
210011	NM_033409.4(SLC52A3):c.49T>C (p.Trp17Arg)	SLC52A3	Pathogenic	no assertion criteria provided
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
2154127	NM_033409.4(SLC52A3):c.408C>G (p.Tyr136Ter)	SLC52A3	Pathogenic	criteria provided, single submitter
2785607	NM_033409.4(SLC52A3):c.293G>A (p.Trp98Ter)	SLC52A3	Pathogenic	criteria provided, single submitter
2815117	NM_033409.4(SLC52A3):c.51G>A (p.Trp17Ter)	SLC52A3	Pathogenic	criteria provided, single submitter
2815140	NM_033409.4(SLC52A3):c.790_791del (p.Ser264fs)	SLC52A3	Pathogenic	criteria provided, single submitter
2920552	NM_033409.4(SLC52A3):c.853C>T (p.Gln285Ter)	SLC52A3	Pathogenic	criteria provided, single submitter
3248316	NC_000020.10:g.(?745957)(749607_?)del	SLC52A3	Pathogenic	criteria provided, single submitter
4710522	NM_033409.4(SLC52A3):c.745G>T (p.Glu249Ter)	SLC52A3	Pathogenic	criteria provided, single submitter
4712184	NM_033409.4(SLC52A3):c.317dup (p.Ala107fs)	SLC52A3	Pathogenic	criteria provided, single submitter
623230	NM_033409.4(SLC52A3):c.753del (p.Val252fs)	SLC52A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
640455	NC_000020.11:g.(?761006)(765794_?)del	SLC52A3	Pathogenic	criteria provided, single submitter
139	NM_033409.4(SLC52A3):c.1325_1326del (p.Leu442fs)	SLC52A3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1709238	NM_033409.4(SLC52A3):c.742del (p.Trp248fs)	SLC52A3	Likely pathogenic	criteria provided, single submitter
2427133	NC_000020.10:g.(?744142)(745909_?)del	SLC52A3	Likely pathogenic	criteria provided, single submitter
2583157	NM_033409.4(SLC52A3):c.374C>T (p.Thr125Ile)	SLC52A3	Likely pathogenic	criteria provided, single submitter
3383371	NM_033409.4(SLC52A3):c.662del (p.Leu221fs)	SLC52A3	Likely pathogenic	criteria provided, single submitter
488380	NM_033409.4(SLC52A3):c.1316G>A (p.Gly439Asp)	SLC52A3	Likely pathogenic	criteria provided, single submitter
1315573	NM_033409.4(SLC52A3):c.710C>T (p.Ala237Val)	SLC52A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
SLC52A3	Definitive	Autosomal recessive	Brown-Vialetto-van Laere syndrome 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC52A3	Orphanet:572550	RFVT3-related riboflavin transporter deficiency
SLC52A2	Orphanet:572543	RFVT2-related riboflavin transporter deficiency

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC52A3	HGNC:16187	ENSG00000101276	Q9NQ40	Solute carrier family 52, riboflavin transporter, member 3	gencc,clinvar
SCRT2	HGNC:15952	ENSG00000215397	Q9NQ03	Transcriptional repressor scratch 2	clinvar
SLC52A2	HGNC:30224	ENSG00000185803	Q9HAB3	Solute carrier family 52, riboflavin transporter, member 2	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.
SCRT2	Transcriptional repressor scratch 2	May be involved in transcriptional regulation.
SLC52A2	Solute carrier family 52, riboflavin transporter, member 2	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: 1 · Unknown: 3 · 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
Transcription factor	1	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC52A3	Other/Unknown	no		Riboflavin_transptr
SCRT2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf,
SLC52A2	Other/Unknown	no		Riboflavin_transptr
LINC01409	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of transverse colon	2
left testis	1
right testis	1
cortical plate	1
ganglionic eminence	1
primary visual cortex	1
right hemisphere of cerebellum	1
stromal cell of endometrium	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
SCRT2	33	tissue_specific	yes	ganglionic eminence, cortical plate, primary visual cortex
SLC52A2	134	ubiquitous	marker	mucosa of transverse colon, stromal cell of endometrium, right hemisphere of cerebellum
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
SLC52A2	877
SLC52A3	864
SCRT2	653
LINC01409	0

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC52A3	Q9NQ40	1
SLC52A2	Q9HAB3	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SCRT2	Q9NQ03	57.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 4 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
Vitamin B2 (riboflavin) metabolism	2	1631.4×	1e-06	SLC52A3, SLC52A2
Metabolism of water-soluble vitamins and cofactors	2	181.3×	6e-05	SLC52A3, SLC52A2
Metabolism of vitamins and cofactors	2	116.5×	1e-04	SLC52A3, SLC52A2
Metabolism	2	11.6×	0.007	SLC52A3, SLC52A2

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
riboflavin transport	2	2808.7×	1e-06	SLC52A3, SLC52A2
riboflavin metabolic process	2	2246.9×	1e-06	SLC52A3, SLC52A2
flavin adenine dinucleotide biosynthetic process	1	2808.7×	0.001	SLC52A3
regulation of neuron migration	1	208.1×	0.009	SCRT2
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	193.7×	0.009	SCRT2
cellular response to heat	1	114.6×	0.013	SLC52A3
sensory perception of sound	1	33.6×	0.038	SLC52A3
regulation of DNA-templated transcription	1	10.5×	0.104	SCRT2
negative regulation of transcription by RNA polymerase II	1	5.9×	0.160	SCRT2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
SCRT2	0	0
SLC52A2	0	0
LINC01409	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	4	SLC52A3, SCRT2, SLC52A2, LINC01409

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC52A3	0	—
SCRT2	0	—
SLC52A2	0	—
LINC01409	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.