SLC52A3

Chr 20AR

solute carrier family 52 member 3

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

NCBI Gene: 113278 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.802 OMIM phenotypes

Clinical Summary— SLC52A3

🧬

Gene-Disease Validity (ClinGen)

Brown-Vialetto-van Laere syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

34 unique Pathogenic / Likely Pathogenic· 225 VUS of 500 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — SLC52A3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC52A3-related Brown-Vialetto-Van Laere syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7326th %ile

GOF

0.6735th %ile

LOF

0.2289th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic13

VUS225

Likely Benign187

Benign29

Conflicting18

Pathogenic

Likely Pathogenic

225

VUS

187

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	3	2	0	21
Likely Pathogenic	6	6	1	0	13
VUS	6	212	7	0	225
Likely Benign	0	6	37	144	187
Benign	0	3	18	8	29
Conflicting	—				18
Total	28	230	65	152	493

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

View in ClinVar →

49 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap SLC52A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →