SLC52A2

Chr 8AR

solute carrier family 52 member 2

Also known as: BVVLS2, D15Ertd747e, GPCR41, GPR172A, HuPAR-1, PAR1, RFT3, RFVT2

NCBI Gene: 79581 ENSG00000185803 UniProt: Q9HAB3 OMIM: 607882

This protein transports riboflavin (vitamin B2) across cell membranes, particularly in brain tissue, where riboflavin is processed into essential coenzymes FMN and FAD for cellular metabolism. Mutations cause Brown-Vialetto-Van Laere syndrome 2, an autosomal recessive progressive neurologic disorder characterized by deafness, bulbar dysfunction, and axial and limb hypotonia. The pathogenic mechanism involves gain-of-function mutations that disrupt normal riboflavin transport.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a membrane protein which belongs to the riboflavin transporter family. In humans, riboflavin must be obtained by intestinal absorption because it cannot be synthesized by the body. The water-soluble vitamin riboflavin is processed to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which then act as intermediaries in many cellular metabolic reactions. Paralogous members of the riboflavin transporter gene family are located on chromosomes 17 and 20. Unlike other members of this family, this gene has higher expression in brain tissue than small intestine. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. Mutations in this gene have been associated with Brown-Vialetto-Van Laere syndrome 2 - an autosomal recessive progressive neurologic disorder characterized by deafness, bulbar dysfunction, and axial and limb hypotonia. [provided by RefSeq, Jul 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.971 OMIM phenotype

Clinical Summary— SLC52A2

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Gene-Disease Validity (ClinGen)

Brown-Vialetto-van Laere syndrome 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

45 unique Pathogenic / Likely Pathogenic· 275 VUS of 581 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC52A2

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?

0.97LOEUF

pLI 0.002

Z-score 1.63

OE 0.49 (0.27–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.85Z-score

OE missense 1.15 (1.04–1.26)

300 obs / 261.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.49 (0.27–0.97)

0≤0.351.4

Missense OE?1.15 (1.04–1.26)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 6 / 12.1Missense obs/exp: 300 / 261.5Syn Z: -3.13

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC52A2-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.

0.7230th %ile

GOF

0.76top 25%

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

581 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26

Likely Pathogenic19

VUS275

Likely Benign215

Benign12

Conflicting21

Pathogenic

Likely Pathogenic

275

VUS

215

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	17	8	1	0	26
Likely Pathogenic	7	12	0	0	19
VUS	3	259	8	5	275
Likely Benign	0	5	42	168	215
Benign	0	0	7	5	12
Conflicting	—				21
Total	27	284	58	178	568

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

View in ClinVar →

56 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap SLC52A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →