SLC52A1

Chr 17AD

solute carrier family 52 member 1

Also known as: GPCR42, GPR172B, PAR2, RBFVD, RFT1, RFVT1, hRFT1, huPAR-2

NCBI Gene: 55065 ENSG00000132517 UniProt: Q9NWF4 OMIM: 607883

This protein is a plasma membrane transporter that mediates cellular uptake of vitamin B2 (riboflavin), which is essential for biochemical oxidation-reduction reactions in carbohydrate, lipid, and amino acid metabolism. Mutations cause autosomal dominant riboflavin deficiency, which can manifest as maternal riboflavin deficiency during pregnancy. The gene shows low constraint to loss-of-function variation (pLI near zero), consistent with the dominant inheritance pattern where single functional copies may be insufficient for normal vitamin B2 transport.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

MultiplemechanismADLOEUF 1.511 OMIM phenotype

Clinical Summary— SLC52A1

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Gene-Disease Validity (ClinGen)

maternal riboflavin deficiency · ADModerate

Moderate evidence — consider for supplementary testing

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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

26 unique Pathogenic / Likely Pathogenic· 185 VUS of 323 total submissions

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GeneReview available — SLC52A1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.51LOEUF

pLI 0.000

Z-score 0.39

OE 0.87 (0.52–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

0.05Z-score

OE missense 0.99 (0.89–1.10)

251 obs / 253.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.87 (0.52–1.51)

0≤0.351.4

Missense OE0.99 (0.89–1.10)

0≤0.61.4

Synonymous OE0.99

0≤1.21.6

LoF obs/exp: 9 / 10.3Missense obs/exp: 251 / 253.4Syn Z: 0.07

0.6938th %ile

GOF

0.72top 25%

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

LOF1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

LOFWe postulate that haploinsufficiency of this riboflavin transporter causes mild riboflavin deficiency, and when coupled with nutritional riboflavin deficiency in pregnancy, resulted in the transient riboflavin-responsive disease seen in her newborn infant.PMID:21089064

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