Brown-Vialetto-van Laere syndrome 2

Summary

Brown-Vialetto-van Laere syndrome 2 (MONDO:0013867) is a disease caused by SLC52A2 (GenCC Definitive), with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC52A2 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 476

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 2
Mondo ID	MONDO:0013867
OMIM	614707
Orphanet	572550
DOID	DOID:0080786
NCIT	C183529
UMLS	C3553538
MedGen	766452
GARD	0012861
Is cancer (heuristic)	no

Also known as: Brown-Vialetto-van Laere syndrome 2 · Brown-Vialetto-van Laere syndrome caused by mutation in SLC52A2 · Brown-Vialetto-Van Laere syndrome type 2 · BVVLS2 · SLC52A2 Brown-Vialetto-van Laere syndrome

Data availability: 476 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

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 2

Related subtypes (2): progressive bulbar palsy, Brown-Vialetto-van Laere syndrome 1

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

476 retrieved; paginated sample, class counts are floors:

210 uncertain significance, 192 likely benign, 26 pathogenic, 20 conflicting classifications of pathogenicity, 8 benign/likely benign, 6 benign, 6 likely pathogenic, 6 pathogenic/likely pathogenic, 2 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1454990	NC_000008.10:g.(?144295143)(145701139_?)del	ADCK5	Pathogenic	criteria provided, single submitter
1070775	NM_001363118.2(SLC52A2):c.593G>A (p.Trp198Ter)	SLC52A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1458358	NM_001363118.2(SLC52A2):c.279_283del (p.Leu94fs)	SLC52A2	Pathogenic	criteria provided, single submitter
188051	NM_001363118.2(SLC52A2):c.808C>T (p.Gln270Ter)	SLC52A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1975679	NM_001363118.2(SLC52A2):c.327dup (p.His110fs)	SLC52A2	Pathogenic	criteria provided, single submitter
210038	NM_001363118.2(SLC52A2):c.383C>T (p.Ser128Leu)	SLC52A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210041	NM_001363118.2(SLC52A2):c.935T>C (p.Leu312Pro)	SLC52A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210042	NM_001363118.2(SLC52A2):c.1088C>T (p.Pro363Leu)	SLC52A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210043	NM_001363118.2(SLC52A2):c.1258G>A (p.Ala420Thr)	SLC52A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
246543	NM_001363118.2(SLC52A2):c.1140del (p.Leu381fs)	SLC52A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2730872	NM_001363118.2(SLC52A2):c.595del (p.Ala199fs)	SLC52A2	Pathogenic	criteria provided, single submitter
2735232	NM_001363118.2(SLC52A2):c.292_293del (p.Leu98fs)	SLC52A2	Pathogenic	criteria provided, single submitter
2840454	NM_001363118.2(SLC52A2):c.54_55del (p.Phe19fs)	SLC52A2	Pathogenic	criteria provided, single submitter
2847488	NM_001363118.2(SLC52A2):c.543del (p.Gly182fs)	SLC52A2	Pathogenic	criteria provided, single submitter
35470	NM_001363118.2(SLC52A2):c.916G>A (p.Gly306Arg)	SLC52A2	Pathogenic	criteria provided, multiple submitters, no conflicts
3710640	NM_001363118.2(SLC52A2):c.545del (p.Gly182fs)	SLC52A2	Pathogenic	criteria provided, single submitter
39576	NM_001363118.2(SLC52A2):c.368T>C (p.Leu123Pro)	SLC52A2	Pathogenic	criteria provided, single submitter
39577	NM_001363118.2(SLC52A2):c.1016T>C (p.Leu339Pro)	SLC52A2	Pathogenic	criteria provided, multiple submitters, no conflicts
40231	NM_001363118.2(SLC52A2):c.155C>T (p.Ser52Phe)	SLC52A2	Pathogenic	criteria provided, single submitter
419108	NM_001363118.2(SLC52A2):c.149dup (p.Tyr50Ter)	SLC52A2	Pathogenic	criteria provided, multiple submitters, no conflicts
473205	NM_001363118.2(SLC52A2):c.551del (p.Pro184fs)	SLC52A2	Pathogenic	criteria provided, single submitter
4733142	NM_001363118.2(SLC52A2):c.551dup (p.Leu185fs)	SLC52A2	Pathogenic	criteria provided, single submitter
4752930	NM_001363118.2(SLC52A2):c.916G>C (p.Gly306Arg)	SLC52A2	Pathogenic	criteria provided, single submitter
572260	NM_001363118.2(SLC52A2):c.1094del (p.Leu365fs)	SLC52A2	Pathogenic	criteria provided, single submitter
659550	NM_001363118.2(SLC52A2):c.1076_1079del (p.Leu359fs)	SLC52A2	Pathogenic	criteria provided, single submitter
660959	NM_001363118.2(SLC52A2):c.751C>T (p.Gln251Ter)	SLC52A2	Pathogenic	criteria provided, single submitter
830619	NC_000008.11:g.(?144358571)(144361296_?)del	SLC52A2	Pathogenic	criteria provided, single submitter
854483	NM_001363118.2(SLC52A2):c.1030_1031del (p.Leu344fs)	SLC52A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929820	NM_001363118.2(SLC52A2):c.402CTT[1] (p.Phe135del)	SLC52A2	Pathogenic	no assertion criteria provided
949075	NM_001363118.2(SLC52A2):c.1137G>A (p.Trp379Ter)	SLC52A2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SLC52A2	Definitive	Autosomal recessive	Brown-Vialetto-van Laere syndrome 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC52A2	Orphanet:572543	RFVT2-related riboflavin transporter deficiency
DGAT1	Orphanet:329242	Congenital chronic diarrhea with protein-losing enteropathy

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
SLC52A2	HGNC:30224	ENSG00000185803	Q9HAB3	Solute carrier family 52, riboflavin transporter, member 2	gencc,clinvar
ADCK5	HGNC:21738	ENSG00000173137	Q3MIX3	Uncharacterized aarF domain-containing protein kinase 5	clinvar
DGAT1	HGNC:2843	ENSG00000185000	O75907	Diacylglycerol O-acyltransferase 1	clinvar
MIR661	HGNC:32917	ENSG00000207574		microRNA 661	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
ADCK5	Uncharacterized aarF domain-containing protein kinase 5	The function of this protein is not yet clear.
DGAT1	Diacylglycerol O-acyltransferase 1	Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.5

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
Kinase	1	6.9×	0.410
Enzyme (other)	1	3.0×	0.441
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC52A2	Other/Unknown	no		Riboflavin_transptr
ADCK5	Kinase	yes		ABC1_dom, Kinase-like_dom_sf, ADCK1_dom
DGAT1	Enzyme (other)	yes	2.3.1.20	MBOAT_fam, Oat_ACAT_DAG_ARE, Diacylglycerol_acylTrfase1
MIR661	Other/Unknown	no

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of transverse colon	3
right hemisphere of cerebellum	2
duodenum	2
stromal cell of endometrium	1
right adrenal gland cortex	1
adrenal tissue	1
blood	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC52A2	134	ubiquitous	marker	mucosa of transverse colon, stromal cell of endometrium, right hemisphere of cerebellum
ADCK5	136	ubiquitous	marker	mucosa of transverse colon, duodenum, right hemisphere of cerebellum
DGAT1	134	ubiquitous	marker	duodenum, mucosa of transverse colon, right adrenal gland cortex
MIR661	89		yes	adrenal tissue, vermiform appendix, blood

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DGAT1	2,407
ADCK5	978
SLC52A2	877
MIR661	0

Intra-cohort edges

A	B	Sources
ADCK5	SLC52A2	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DGAT1	O75907	5
SLC52A2	Q9HAB3	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADCK5	Q3MIX3	82.08

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Acyl chain remodeling of DAG and TAG	1	815.7×	0.004	DGAT1
Vitamin B2 (riboflavin) metabolism	1	815.7×	0.004	SLC52A2
Triglyceride biosynthesis	1	335.9×	0.007	DGAT1
Metabolism of water-soluble vitamins and cofactors	1	90.6×	0.019	SLC52A2
Metabolism of vitamins and cofactors	1	58.3×	0.024	SLC52A2
Neutrophil degranulation	1	11.5×	0.099	DGAT1
Metabolism	1	5.8×	0.165	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 2 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	1	2106.5×	0.003	SLC52A2
riboflavin metabolic process	1	1685.2×	0.003	SLC52A2
long-chain fatty-acyl-CoA metabolic process	1	1203.7×	0.003	DGAT1
monoacylglycerol biosynthetic process	1	766.0×	0.003	DGAT1
very-low-density lipoprotein particle assembly	1	601.9×	0.003	DGAT1
diacylglycerol metabolic process	1	601.9×	0.003	DGAT1
fatty acid homeostasis	1	468.1×	0.003	DGAT1
triglyceride biosynthetic process	1	366.4×	0.003	DGAT1
lipid storage	1	271.8×	0.004	DGAT1
triglyceride metabolic process	1	221.7×	0.005	DGAT1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ADCK5	NERATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DGAT1	3	3
ADCK5	2	4
SLC52A2	0	0
MIR661	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NERATINIB	4	ADCK5
LINSITINIB	3	ADCK5
PRADIGASTAT	3	DGAT1
PF-04620110	1	DGAT1
AZD-7687	1	DGAT1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DGAT1	130	Binding:130
ADCK5	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DGAT1	2.3.1.20	diacylglycerol O-acyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
DGAT1	130

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

5 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)
NERATINIB	4	ADCK5
LINSITINIB	3	ADCK5
PRADIGASTAT	3	DGAT1
PF-04620110	1	DGAT1
AZD-7687	1	DGAT1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ADCK5
B	Phased (≥1) drug, not yet approved	1	DGAT1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SLC52A2, MIR661

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)
SLC52A2	0	—
MIR661	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.