SLC52A1

protein-coding

solute carrier family 52 member 1, the group of Solute carrier family 52

Gene summary

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]

Previous symbols:

GPR172B

MANE transcript

NM_017986.4

Inheritance

ClinVar variants

U:170B:86

Top phenotype

Riboflavin deficiency

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr17:5,032,600-5,052,009

External References & Databases

Ensembl (ENSG00000132517)

Transcript & Mutation Effects

hg38 • Region Span ~19.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

maternal riboflavin deficiencyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014013

Submitter: Ambry Genetics

ariboflavinosisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0004573

Submitter: PanelApp Australia

ariboflavinosisLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0004573

Submitter: Labcorp Genetics (formerly Invitae)

maternal riboflavin deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014013

Submitter: Orphanet

maternal riboflavin deficiencyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014013

Submitter: ClinGen

SLC52A1 was reported in relation to autosomal dominant maternal riboflavin deficiency in 2011 (Ho et al., PMID 21089064). At least 5 variants (e.g. large deletion, intronic, missense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 5 probands in 3 publications (PMIDs 21089064, 29122468, 37510312). This gene-disease association is supported by expression studies and in vitro functional assays. In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the Fatty Acid Oxidation Disorders GCEP on October 12, 2018. It was reevaluated on May 22, 2026. As a result of this reevaluation, the classification did not change.

Clinical Genomic Database (CGD)

Riboflavin deficiencyAD

Manifestation: Biochemical; Neurologic

Intervention: Biochemical

Rationale: One individual with a heterozygous deletion has been reported, and this was postulated as contributing to transient neonatal-onset glutaric aciduria Type 2 in this individual's offspring,which was reported as being effectively treated by riboflavin therapy

Comments: Theoretically, biallelic variants could contribute to disease similar to that arising from variants in SLC52A2 or SLC52A3

Refs: 17689999; 21089064; 23107375

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC52A1 variants in ClinVar

6 Conditions Cataloged

Vitamin B2 deficiencyTotal: 228

not specifiedTotal: 73

not providedTotal: 18

AriboflavinosisTotal: 16

SLC52A1-related disorderTotal: 9

Maternal riboflavin deficiencyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017986.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	73 clinvar	2 clinvar	77
missense			152 clinvar	10 clinvar		162
nonsense			2 clinvar			2
start loss			1 clinvar			1
frameshift			13 clinvar	1 clinvar		14
splice donor/acceptor (+/-2bp)						0
Total	0	0	170	84	2	256

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017986.4	RefSeq	NP_060456.3	4	MANE Select
ENST00000254853.10	Ensembl	ENSP00000254853.5	4	MANE Select
NM_001104577.2	RefSeq	NP_001098047.1	4	Standard
ENST00000424747.1	Ensembl	ENSP00000399979.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism
Vitamin B2 (riboflavin) metabolism
Metabolism of water-soluble vitamins and cofactors
Metabolism of vitamins and cofactors

Biological Process

riboflavin metabolic process
riboflavin transport
viral entry into host cell

Molecular Function

virus receptor activity
riboflavin transmembrane transporter activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000424747
Coding exons: 4
Length: 19410
Individuals with no LoFs: 125646
Homozygous LoFs: 0
Heterozygous LoFs: 101
Defined: 125747
p: 0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0538	251	253	0.990	0.0000137	2781
Missense (PolyPhen)		89	84.03	1.0591		1032
Synonymous	0.0658	121	122	0.992	0.00000694	1103
Loss of Function	0.388	9	10.3	0.870	4.44e-7	116

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0020	0.0020	notable
Latino/Admixed American	0.00075	0.00067	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00027	0.00024	rare
South Asian	0.00043	0.00042	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Riboflavin transporter. Riboflavin transport is Na(+)- independent but moderately pH-sensitive. Activity is strongly inhibited by riboflavin analogs, such as lumiflavin. Weakly inhibited by flavin adenine dinucleotide (FAD). In case of infection by retroviruses, acts as a cell receptor to retroviral envelopes similar to the porcine endogenous retrovirus (PERV-A). {ECO:0000269|PubMed:12740431, ECO:0000269|PubMed:20463145}.;

Recessive Scores

pRec: 0.0920

Intolerance Scores

RVIS EVS: 0.31
RVIS percentile EVS: 72.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium