SLC52A1

Chr 17AD

solute carrier family 52 member 1

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

NCBI Gene: 55065ENSG00000132517UniProt: Q9NWF4

Biological redox reactions require electron donors and acceptor. Vitamin B2 is the source for the flavin in flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) which are common redox reagents. This gene encodes a member of the riboflavin (vitamin B2) transporter family. Haploinsufficiency of this protein can cause maternal riboflavin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2013]

Primary Disease Associations & Inheritance

Riboflavin deficiencyMIM #615026
AD
318
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC52A1
🧬
Gene-Disease Validity (ClinGen)
maternal riboflavin deficiency · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 185 VUS of 318 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.
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?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.
0.05Z-score
OE missense 0.99 (0.89–1.10)
251 obs / 253.4 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.0.87 (0.52–1.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.89–1.10)
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.0.99
0≤1.21.6
LoF obs/exp: 9 / 10.3Missense obs/exp: 251 / 253.4Syn Z: 0.07

ClinVar Variant Classifications

318 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS185
Likely Benign84
Benign17
Conflicting6
24
Pathogenic
2
Likely Pathogenic
185
VUS
84
Likely Benign
17
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
23
0
24
Likely Pathogenic
0
0
2
0
2
VUS
14
152
17
2
185
Likely Benign
0
5
8
71
84
Benign
0
4
9
4
17
Conflicting
—6
Total141625977318

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC52A1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Riboflavin deficiency

MIM #615026

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SLC52A1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Riboflavin 1 Transporter Deficiency: Novel SLC52A1 Variants and Expansion of the Phenotypic Spectrum.
Grünert SC et al.·Genes (Basel)
2023Case report
Disorders of flavin adenine dinucleotide metabolism: MADD and related deficiencies.
Mereis M et al.·Int J Biochem Cell Biol
2021Review
Whole-exome Sequencing Identifies SLC52A1 and ZNF106 Variants as Novel Genetic Risk Factors for (Early) Multiple-organ Failure in Acute Pancreatitis.
van den Berg FF et al.·Ann Surg
2022
Child Neurology: Five-Year Update on Siblings With Riboflavin Transporter Deficiency: Stable Visual and Neurologic Status With Continued Riboflavin Therapy.
O'Brien MA et al.·Neurology
2024Case report
The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives.
Bosch AM et al.·Orphanet J Rare Dis
2012Review
Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome.
Nalini A et al.·J Neurol Sci
2013
Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer.
Zhang X et al.·Biomed Res Int
2021
Flavin adenine dinucleotide synthase deficiency due to FLAD1 mutation presenting as multiple acyl-CoA dehydrogenation deficiency-like disease: A case report.
Yamada K et al.·Brain Dev
2019Case report
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