SLC52A3

Chr 20AR

solute carrier family 52 member 3

Also known as: BVVLS, BVVLS1, C20orf54, RFT2, RFVT3, bA371L19.1, hRFT2

NCBI Gene: 113278ENSG00000101276UniProt: Q9NQ40

This gene encodes a riboflavin transporter protein that is strongly expressed in the intestine and likely plays a role in intestinal absorption of riboflavin. The protein is predicted to have eleven transmembrane domains and a cell surface localization signal in the C-terminus. Mutations at this locus have been associated with Brown-Vialetto-Van Laere syndrome and Fazio-Londe disease. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

?Fazio-Londe diseaseMIM #211500
AR
Brown-Vialetto-Van Laere syndrome 1MIM #211530
AR
565
ClinVar variants
13
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— SLC52A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 34 VUS of 565 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.019
Z-score 2.08
OE 0.38 (0.20–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.25Z-score
OE missense 0.79 (0.70–0.88)
214 obs / 271.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.20–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.70–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 5 / 13.1Missense obs/exp: 214 / 271.9Syn Z: -0.52

ClinVar Variant Classifications

565 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS34
Likely Benign51
10
Pathogenic
3
Likely Pathogenic
34
VUS
51
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
8
0
10
Likely Pathogenic
1
0
2
0
3
VUS
1
27
6
0
34
Likely Benign
0
1
9
41
51
Benign
0
0
0
0
0
Total428254198

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC52A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC52A3-related Brown-Vialetto-Van Laere syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEar
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Fazio-Londe disease

MIM #211500

Molecular basis of disorder known

Autosomal recessive

Brown-Vialetto-Van Laere syndrome 1

MIM #211530

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.
Ge YJ et al.·Alzheimers Dement
2024Meta-analysis
SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.
Mir A et al.·Hum Genet
2022
Brown-Vialetto-Van Laere and Fazio-Londe syndromes: SLC52A3 mutations with puzzling phenotypes and inheritance.
Gayathri S et al.·Eur J Neurol
2021
Brown-Vialetto-Van Laere syndrome patients with unusual phenotypes from Indian ethnicity: Functional analysis of clinical variants in SLC52A2 and SLC52A3 genes.
Gayathri S et al.·Brain Dev
2025Cohort
Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals.
Xu H et al.·Am J Respir Crit Care Med
2022
Atypical presentations in an RTD patient and report of novel SLC52A3 and SLC52A2 mutations.
Sabeghi D et al.·Acta Neurol Belg
2024Case report
Rare Diseases Linked to Mutations in Vitamin Transporters Expressed in the Human Blood-Brain Barrier.
Yee SW et al.·Clin Pharmacol Ther
2024Review
Mutation screening of SLC52A3, C19orf12, and TARDBP in Iranian ALS patients.
Khani M et al.·Neurobiol Aging
2019Cohort
Functional variation of SLC52A3 rs13042395 predicts survival of Chinese gastric cancer patients.
Qu X et al.·J Cell Mol Med
2020Cohort
Riboflavin in Neurological Diseases: A Narrative Review.
Plantone D et al.·Clin Drug Investig
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools