SLC52A3

Chr 20AR

solute carrier family 52 member 3

ENSG00000101276 UniProt: Q9NQ40 OMIM: 613350

This gene encodes a riboflavin transporter protein that facilitates intestinal absorption of riboflavin and localizes to the apical cell membrane with eleven transmembrane domains. Autosomal recessive mutations cause Brown-Vialetto-Van Laere syndrome 1 and Fazio-Londe disease through a dominant-negative mechanism. The protein's disrupted function leads to riboflavin deficiency affecting neuronal metabolism and survival.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 (PubMed:20463145, PubMed:22273710, PubMed:24264046, PubMed:27702554). Humans are unable to synthesize vitamin B2/riboflavin and must obtain it via intestinal absorption (PubMed:20463145)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Fazio-Londe diseaseMIM #211500

Brown-Vialetto-Van Laere syndrome 1MIM #211530

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Brown-Vialetto-van Laere syndrome 1 · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.019

Z-score 2.08

OE 0.38 (0.20–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.25Z-score

OE missense 0.79 (0.70–0.88)

214 obs / 271.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.20–0.80)

0≤0.351.4

Missense OE?0.79 (0.70–0.88)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 5 / 13.1Missense obs/exp: 214 / 271.9Syn Z: -0.52

Background carrier burden — how many people carry a rare variant somewhere in SLC52A3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

747 rare PASS variants

Rare truncating (LoF)

1 in 970

69 rare PASS variants

Rare synonymous (reference)

1 in 190

265 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC52A3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 72	1 in 860
South Asian	~43k	1 in 80	1 in 7,000
Remaining (unassigned)	~30k	1 in 71	1 in 1,400
European (Finnish)	~27k	1 in 200	1 in 2,100
Admixed American	~22k	1 in 95	1 in 950
African / African American	~21k	1 in 74	1 in 3,700
East Asian	~20k	1 in 170	none seen
Ashkenazi Jewish	~13k	1 in 450	1 in 510
Middle Eastern	~2,884	1 in 81	≈ 1 in 2,200

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓