SLC52A2

Summary

SLC52A2 (solute carrier family 52 member 2, HGNC:30224) is a protein-coding gene on chromosome 8q24.3, encoding Solute carrier family 52, riboflavin transporter, member 2 (Q9HAB3). Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism.

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.

Source: NCBI Gene 79581 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Brown-Vialetto-van Laere syndrome 2 (Definitive, ClinGen)
• Clinical variants (ClinVar): 578 total — 26 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_001363118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30224
Approved symbol	SLC52A2
Name	solute carrier family 52 member 2
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11856, PAR1, GPCR41, D15Ertd747e, RFVT2, hRFT3, RFT3, HuPAR-1
Ensembl gene	ENSG00000185803
Ensembl biotype	protein_coding
OMIM	607882
Entrez	79581

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 40 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000329994, ENST00000402965, ENST00000524541, ENST00000526338, ENST00000526752, ENST00000526779, ENST00000526891, ENST00000527078, ENST00000530047, ENST00000532815, ENST00000533662, ENST00000534725, ENST00000643944, ENST00000644270, ENST00000674779, ENST00000674821, ENST00000674870, ENST00000674929, ENST00000675121, ENST00000675280, ENST00000675292, ENST00000675597, ENST00000675787, ENST00000675888, ENST00000675998, ENST00000676094, ENST00000676358, ENST00000876534, ENST00000876535, ENST00000876536, ENST00000876537, ENST00000913643, ENST00000913644, ENST00000913645, ENST00000913646, ENST00000913647, ENST00000913648, ENST00000948695, ENST00000948696, ENST00000948697, ENST00000948698, ENST00000948699, ENST00000948700, ENST00000948701, ENST00000948702, ENST00000948703

RefSeq mRNA: 8 — MANE Select: NM_001363118 NM_001253815, NM_001253816, NM_001363118, NM_001363120, NM_001363121, NM_001363122, NM_001410949, NM_024531

CCDS: CCDS6423, CCDS94364, CCDS94365

Canonical transcript exons

ENST00000643944 — 5 exons

Exon	Start	End
ENSE00000000092	144360803	144361272
ENSE00001330982	144359184	144359423
ENSE00001660208	144360590	144360713
ENSE00003625062	144359623	144360493
ENSE00003815130	144358613	144359065

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.6793 / max 135.4164, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91502	16.5414	1801
91503	0.9865	590
91501	0.7384	477
205402	0.3199	146
91500	0.0931	49

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.84	gold quality
stromal cell of endometrium	CL:0002255	92.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.38	gold quality
lower esophagus mucosa	UBERON:0035834	91.16	gold quality
cerebellar hemisphere	UBERON:0002245	90.59	gold quality
cerebellum	UBERON:0002037	90.54	gold quality
cerebellar cortex	UBERON:0002129	90.52	gold quality
transverse colon	UBERON:0001157	90.27	gold quality
granulocyte	CL:0000094	90.05	gold quality
apex of heart	UBERON:0002098	89.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.43	gold quality
body of stomach	UBERON:0001161	88.96	gold quality
metanephros cortex	UBERON:0010533	88.82	gold quality
body of pancreas	UBERON:0001150	88.70	gold quality
spleen	UBERON:0002106	88.69	gold quality
esophagus mucosa	UBERON:0002469	88.17	gold quality
left adrenal gland cortex	UBERON:0035825	88.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.01	gold quality
left adrenal gland	UBERON:0001234	88.00	gold quality
omental fat pad	UBERON:0010414	87.86	gold quality
right adrenal gland	UBERON:0001233	87.77	gold quality
right testis	UBERON:0004534	87.72	gold quality
left testis	UBERON:0004533	87.63	gold quality
minor salivary gland	UBERON:0001830	87.58	gold quality
saliva-secreting gland	UBERON:0001044	87.48	gold quality
upper lobe of left lung	UBERON:0008952	87.48	gold quality
small intestine	UBERON:0002108	87.45	gold quality
placenta	UBERON:0001987	87.43	gold quality
colon	UBERON:0001155	87.23	gold quality
right adrenal gland cortex	UBERON:0035827	87.19	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting SLC52A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-1915-5P	95.25	65.78	571
HSA-MIR-6514-5P	95.07	66.02	655

Literature-anchored findings (GeneRIF, showing 16)

• summary of recent findings on the cloning, nomenclature, functional characterization and genetic diseases of RFVT1/SLC52A1, RFVT2/SLC52A2 and RFVT3/SLC52A3 [review] (PMID:23506902)
• data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. (PMID:24139842)
• We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression (PMID:24253200)
• Mutations in SLC52A2 result in a recognizable phenotype distinct from Brown-Vialetto-Van-Laere syndrome. (PMID:24616084)
• A novel SLC52A2 mutation identified in a family with spinocerebellar ataxia with blindness and deafness. (PMID:26669662)
• These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk. (PMID:26791833)
• This study showed that Auditory neuropathy in Brown-Vialetto-Van Laere syndrome due to riboflavin transporter RFVT2 deficiency and improved by riboflavin treatment. (PMID:26918385)
• Eight mutations in SLC52a2 were associated with Brown-Vialetto-Van Laere syndrome. (PMID:29053833)
• Whole exome sequencing identified a homozygous likely pathogenic variant in SCL52A3 (c.1223G>A; p.Gly408Asp). We report two new patients with riboflavin transporter deficiency, caused by mutations in two different riboflavin transporter genes. (PMID:29193829)
• This is the second report of the genotype-phenotype correlation between this syndrome named spinocerebellar ataxia with blindness and deafness type 2 (SCABD2) and SLC52A2 gene. (PMID:29287867)
• RFVT2 gene and protein expression levels were higher in DLD-1 and HT-29 compared to Caco2 cells. In tumor tissues of patients with CRC, RFVT2 gene expression levels were increased, while protein expression was reduced, with a small reduction in riboflavin amount. (PMID:29715086)
• Reports on 109 patients with a genetically confirmed diagnosis of riboflavin transporter deficiency are summarized in order to highlight commonly presenting clinical features and possible differences between patients with pathogenic SLC52A2 (RTD2) or SLC52A3 (RTD3) mutations. [review] (PMID:30793323)
• Mitochondrial and Peroxisomal Alterations Contribute to Energy Dysmetabolism in Riboflavin Transporter Deficiency. (PMID:32855765)
• Functional Study of the Human Riboflavin Transporter 2 Using Proteoliposomes System. (PMID:33751428)
• Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2. (PMID:34428344)
• Retrograde response to mitochondrial dysfunctions associated to LOF variations in FLAD1 exon 2: unraveling the importance of RFVT2. (PMID:36480241)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc52a2	ENSDARG00000102035
mus_musculus	Slc52a2	ENSMUSG00000022560
rattus_norvegicus	Slc52a2	ENSRNOG00000032561
drosophila_melanogaster	Rift	FBGN0039882
caenorhabditis_elegans		WBGENE00021626
caenorhabditis_elegans		WBGENE00044637

Paralogs (2): SLC52A3 (ENSG00000101276), SLC52A1 (ENSG00000132517)

Protein

Protein identifiers

Solute carrier family 52, riboflavin transporter, member 2 — Q9HAB3 (reviewed: Q9HAB3)

Alternative names: Porcine endogenous retrovirus A receptor 1, Protein GPR172A, Riboflavin transporter 3

All UniProt accessions (12): A0A6Q8PFH5, A0A6Q8PFQ5, A0A6Q8PG35, A0A6Q8PGB9, A0A6Q8PGE2, A0A6Q8PHF8, E9PIX2, E9PJC1, E9PKE4, E9PPS0, E9PRC3, Q9HAB3

UniProt curated annotations — full annotation on UniProt →

Function. Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism. Humans are unable to synthesize vitamin B2/riboflavin and must obtain it via intestinal absorption. May also act as a receptor for 4-hydroxybutyrate. (Microbial infection) In case of infection by retroviruses, acts as a cell receptor to retroviral envelopes similar to the porcine endogenous retrovirus (PERV-A).

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in brain, fetal brain and salivary gland. Weakly expressed in other tissues.

Disease relevance. Brown-Vialetto-Van Laere syndrome 2 (BVVLS2) [MIM:614707] An autosomal recessive progressive neurologic disorder characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting resulting in respiratory insufficiency and loss of independent ambulation. Because it results from a defect in riboflavin metabolism, some patients may benefit from high-dose riboflavin supplementation. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. 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) and flavin mononucleotide (FMN).

Similarity. Belongs to the riboflavin transporter family.

RefSeq proteins (8): NP_001240744, NP_001240745, NP_001350047, NP_001350049, NP_001350050, NP_001350051, NP_001397878, NP_078807 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009357	Riboflavin_transptr	Family

Pfam: PF06237

Catalyzed reactions (Rhea), 1 shown:

• riboflavin(in) = riboflavin(out) (RHEA:35015)

UniProt features (48 total): helix 17, transmembrane region 11, sequence variant 10, strand 4, turn 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8XSM	ELECTRON MICROSCOPY	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAB3-F1	84.50	0.61

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196843	Vitamin B2 (riboflavin) metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 169 (showing top): ELVIDGE_HYPOXIA_DN, WANG_CLIM2_TARGETS_UP, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST, GOBP_VIRAL_LIFE_CYCLE, LIAO_METASTASIS, GOBP_VITAMIN_TRANSPORT, BASAKI_YBX1_TARGETS_UP, ACACTCC_MIR122A, AIYAR_COBRA1_TARGETS_UP, ZHANG_GATA6_TARGETS_DN, SCGGAAGY_ELK1_02, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS

GO Biological Process (3): riboflavin metabolic process (GO:0006771), riboflavin transport (GO:0032218), symbiont entry into host cell (GO:0046718)

GO Molecular Function (4): virus receptor activity (GO:0001618), riboflavin transmembrane transporter activity (GO:0032217), 4-hydroxybutyrate receptor activity (GO:0062124), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
flavin-containing compound metabolic process	1
vitamin transport	1
nitrogen compound transport	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
riboflavin transport	1
vitamin transmembrane transporter activity	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC52A2	FFAR2	O15552	701
SLC52A2	FLAD1	Q8NFF5	657
SLC52A2	SLC25A32	Q9H2D1	595
SLC52A2	ETFDH	Q16134	526
SLC52A2	RFK	Q969G6	465
SLC52A2	FBXL6	Q8N531	456
SLC52A2	TMEM237	Q96Q45	455
SLC52A2	GPR42	O15529	434
SLC52A2	SLC19A3	Q9BZV2	428
SLC52A2	FFAR3	O14843	415
SLC52A2	ETFB	P38117	411
SLC52A2	MROH1	Q8NDA8	389
SLC52A2	ADCK5	Q3MIX3	375
SLC52A2	IGHMBP2	P38935	366
SLC52A2	FFAR1	O14842	360

IntAct

16 interactions, top by confidence:

A	B	Type	Score
SLC52A2	CDC23	psi-mi:“MI:0915”(physical association)	0.560
CDC23	SLC52A2	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	SLC52A2	psi-mi:“MI:0915”(physical association)	0.560
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
SLC52A2	GHITM	psi-mi:“MI:0915”(physical association)	0.400
SLC52A2	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
SLC52A2	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
SPPL2B	GPR89A	psi-mi:“MI:0914”(association)	0.350
SPPL2B	HAS3	psi-mi:“MI:0914”(association)	0.350
LGALS3	SDCBP	psi-mi:“MI:0914”(association)	0.350
SLC52A2	FAM209A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): SLC52A2 (Two-hybrid), SLC52A2 (Affinity Capture-MS), SLC52A2 (Affinity Capture-MS), SLC52A2 (Affinity Capture-RNA), SLC52A2 (Two-hybrid), SLC52A2 (Proximity Label-MS), SLC52A2 (Two-hybrid), SLC52A2 (Two-hybrid), SLC52A2 (Negative Genetic), SLC52A2 (Negative Genetic), SLC52A2 (Negative Genetic), SLC52A2 (Affinity Capture-MS), GHITM (Affinity Capture-MS), SLC52A2 (Affinity Capture-RNA), SLC52A2 (Co-fractionation)

ESM2 similar proteins: A6NGC4, A6NKX4, A6NM10, D3YZZ2, O35595, O46547, O60391, O77808, O95528, P30518, P43119, P46092, P46095, P48044, P48748, Q14626, Q3SYU3, Q3ZAV1, Q4U2R8, Q4W8A3, Q5RF19, Q5U419, Q64385, Q684M3, Q6UXD7, Q6UXT9, Q6YNI2, Q863Y8, Q86SM5, Q8CFZ5, Q8IXF9, Q8WUG5, Q91X56, Q924U0, Q96S37, Q99MF4, Q9BGL8, Q9BZ11, Q9H1Z9, Q9H228

Diamond homologs: B0S5Y3, B5MEV3, B5X4H8, C1BKZ7, D2HSA6, G4SDH4, Q3LFN0, Q4FZU9, Q5E9R1, Q6GMG6, Q863Y7, Q863Y8, Q9D6X5, Q9D8F3, Q9HAB3, Q9NQ40, Q9NWF4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

578 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	12
Uncertain significance	276
Likely benign	205
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070775	NM_001363118.2(SLC52A2):c.593G>A (p.Trp198Ter)	Pathogenic
1458358	NM_001363118.2(SLC52A2):c.279_283del (p.Leu94fs)	Pathogenic
188051	NM_001363118.2(SLC52A2):c.808C>T (p.Gln270Ter)	Pathogenic
1975679	NM_001363118.2(SLC52A2):c.327dup (p.His110fs)	Pathogenic
2730872	NM_001363118.2(SLC52A2):c.595del (p.Ala199fs)	Pathogenic
2735232	NM_001363118.2(SLC52A2):c.292_293del (p.Leu98fs)	Pathogenic
2840454	NM_001363118.2(SLC52A2):c.54_55del (p.Phe19fs)	Pathogenic
2847488	NM_001363118.2(SLC52A2):c.543del (p.Gly182fs)	Pathogenic
3061936	NM_001363118.2(SLC52A2):c.1024dup (p.Leu342fs)	Pathogenic
35470	NM_001363118.2(SLC52A2):c.916G>A (p.Gly306Arg)	Pathogenic
3710640	NM_001363118.2(SLC52A2):c.545del (p.Gly182fs)	Pathogenic
39576	NM_001363118.2(SLC52A2):c.368T>C (p.Leu123Pro)	Pathogenic
39577	NM_001363118.2(SLC52A2):c.1016T>C (p.Leu339Pro)	Pathogenic
40231	NM_001363118.2(SLC52A2):c.155C>T (p.Ser52Phe)	Pathogenic
419108	NM_001363118.2(SLC52A2):c.149dup (p.Tyr50Ter)	Pathogenic
473205	NM_001363118.2(SLC52A2):c.551del (p.Pro184fs)	Pathogenic
4733142	NM_001363118.2(SLC52A2):c.551dup (p.Leu185fs)	Pathogenic
4752930	NM_001363118.2(SLC52A2):c.916G>C (p.Gly306Arg)	Pathogenic
572260	NM_001363118.2(SLC52A2):c.1094del (p.Leu365fs)	Pathogenic
659550	NM_001363118.2(SLC52A2):c.1076_1079del (p.Leu359fs)	Pathogenic
660959	NM_001363118.2(SLC52A2):c.751C>T (p.Gln251Ter)	Pathogenic
830619	NC_000008.11:g.(?144358571)(144361296_?)del	Pathogenic
929820	NM_001363118.2(SLC52A2):c.402CTT[1] (p.Phe135del)	Pathogenic
949075	NM_001363118.2(SLC52A2):c.1137G>A (p.Trp379Ter)	Pathogenic
96702	NM_001363118.2(SLC52A2):c.851C>A (p.Ala284Asp)	Pathogenic
96703	NM_001363118.2(SLC52A2):c.914A>G (p.Tyr305Cys)	Pathogenic
1481986	NM_001363118.2(SLC52A2):c.973T>C (p.Cys325Arg)	Likely pathogenic
1723848	NM_001363118.2(SLC52A2):c.154T>C (p.Ser52Pro)	Likely pathogenic
1747539	NM_001363118.2(SLC52A2):c.1201_1202delinsC (p.Gly401fs)	Likely pathogenic
245818	NM_001363118.2(SLC52A2):c.107T>G (p.Val36Gly)	Likely pathogenic

SpliceAI

3150 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144336050:CTCA:C	donor_loss	1.0000
8:144336051:TCAC:T	donor_loss	1.0000
8:144336053:A:AC	donor_gain	1.0000
8:144336053:AC:A	donor_gain	1.0000
8:144336054:C:CC	donor_gain	1.0000
8:144336054:CC:C	donor_gain	1.0000
8:144336054:CCTTT:C	donor_gain	1.0000
8:144353860:TGGG:T	acceptor_gain	1.0000
8:144353861:GGG:G	acceptor_gain	1.0000
8:144353861:GGGC:G	acceptor_loss	1.0000
8:144353862:GG:G	acceptor_gain	1.0000
8:144353862:GGC:G	acceptor_loss	1.0000
8:144353863:GC:G	acceptor_loss	1.0000
8:144353863:GCT:G	acceptor_loss	1.0000
8:144353864:C:CC	acceptor_gain	1.0000
8:144353864:CTGCG:C	acceptor_loss	1.0000
8:144353865:T:G	acceptor_loss	1.0000
8:144353950:TTAC:T	donor_loss	1.0000
8:144353951:TACCA:T	donor_loss	1.0000
8:144353952:ACCA:A	donor_loss	1.0000
8:144353953:C:CA	donor_loss	1.0000
8:144353953:C:CT	donor_loss	1.0000
8:144353980:TAG:T	donor_gain	1.0000
8:144353981:AGA:A	donor_gain	1.0000
8:144354234:CA:C	donor_gain	1.0000
8:144354234:CACCT:C	donor_gain	1.0000
8:144356046:A:AC	donor_gain	1.0000
8:144356081:A:AC	donor_gain	1.0000
8:144356082:C:CC	donor_gain	1.0000
8:144356085:AACC:A	donor_gain	1.0000

AlphaMissense

2763 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144359952:A:C	S154R	0.975
8:144359954:T:A	S154R	0.975
8:144359954:T:G	S154R	0.975
8:144360123:T:C	F211L	0.968
8:144360125:C:A	F211L	0.968
8:144360125:C:G	F211L	0.968
8:144359886:T:C	F132L	0.966
8:144359888:C:A	F132L	0.966
8:144359888:C:G	F132L	0.966
8:144359895:T:C	F135L	0.963
8:144359897:C:A	F135L	0.963
8:144359897:C:G	F135L	0.963
8:144360387:A:C	S299R	0.962
8:144360389:C:A	S299R	0.962
8:144360389:C:G	S299R	0.962
8:144359941:G:A	G150D	0.961
8:144359352:G:A	G20D	0.959
8:144359940:G:C	G150R	0.959
8:144360857:A:C	S394R	0.959
8:144360859:C:A	S394R	0.959
8:144360859:C:G	S394R	0.959
8:144360666:A:C	S360R	0.956
8:144360668:C:A	S360R	0.956
8:144360668:C:G	S360R	0.956
8:144359357:G:C	G22R	0.955
8:144359934:T:C	F148L	0.953
8:144359936:C:A	F148L	0.953
8:144359936:C:G	F148L	0.953
8:144360078:T:C	F196L	0.953
8:144360080:C:A	F196L	0.953

dbSNP variants (sampled 300 via entrez): RS1001418068 (8:144360211 C>A), RS1001469926 (8:144360404 C>T), RS1002424042 (8:144359138 T>C), RS1003098336 (8:144361058 C>T), RS1004998551 (8:144357637 A>G), RS1009060977 (8:144357039 A>G), RS1009525003 (8:144357292 G>A,C,T), RS1011905400 (8:144357851 G>A,C), RS1012907528 (8:144356741 C>T), RS1013548817 (8:144361553 G>A), RS1015353494 (8:144358778 C>T), RS1016614259 (8:144359916 C>T), RS1017185357 (8:144361613 C>T), RS1018703655 (8:144360877 G>A,C), RS1019069468 (8:144358465 G>A,C)

Disease associations

OMIM: gene MIM:607882 | disease phenotypes: MIM:614707, MIM:211530

GenCC curated gene-disease

Disease	Classification	Inheritance
Brown-Vialetto-van Laere syndrome 2	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Brown-Vialetto-van Laere syndrome 2	Definitive	AR

Mondo (4): Brown-Vialetto-van Laere syndrome 2 (MONDO:0013867), Brown-Vialetto-van Laere syndrome 1 (MONDO:0024537), mitochondrial disease (MONDO:0044970), sensorineural hearing loss disorder (MONDO:0020678)

Orphanet (4): RFVT3-related riboflavin transporter deficiency (Orphanet:572550), Riboflavin transporter deficiency (Orphanet:97229), RFVT2-related riboflavin transporter deficiency (Orphanet:572543), Mitochondrial disease (Orphanet:68380)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000572	Visual loss
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000718	Aggressive behavior
HP:0001171	Split hand
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001283	Bulbar palsy
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001308	Tongue fasciculations
HP:0001992	Organic aciduria
HP:0002015	Dysphagia
HP:0002093	Respiratory insufficiency
HP:0002312	Clumsiness
HP:0002375	Hypokinesia
HP:0002650	Scoliosis
HP:0002751	Kyphoscoliosis
HP:0003676	Progressive
HP:0003690	Limb muscle weakness
HP:0003700	Generalized amyotrophy
HP:0003828	Variable expressivity
HP:0006824	Cranial nerve paralysis
HP:0007141	Sensorimotor neuropathy
HP:0010628	Facial palsy

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC52 family of riboflavin transporters

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	3
Estradiol	affects expression, increases expression	2
Tunicamycin	increases expression	2
Valproic Acid	increases expression, increases methylation	2
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
methacrylaldehyde	affects cotreatment, affects expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Acrolein	increases abundance, affects cotreatment, affects expression	1
Air Pollutants	increases abundance, affects cotreatment, affects expression	1
Vehicle Emissions	increases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases expression, increases abundance	1
Dactinomycin	affects cotreatment, increases expression	1
Methotrexate	affects response to substance	1
Ozone	affects cotreatment, affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2GC	Abcam HeLa SLC52A2 KO	Cancer cell line	Female
CVCL_B3XP	ATCi001-A	Induced pluripotent stem cell	Female
CVCL_D4PY	HCT116-SLC52A2-KO-c4	Cancer cell line	Male
CVCL_D4PZ	HCT116-SLC52A2-KO-c7	Cancer cell line	Male
CVCL_F1UT	HyCyte U-251MG KO-hSLC52A2	Cancer cell line	Male

Clinical trials (associated diseases)

192 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT01655212	PHASE3	TERMINATED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial
NCT02005822	PHASE3	COMPLETED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
NCT03374514	PHASE3	UNKNOWN	Cochlear Electrical Impedance and the Effect of Topical Dexamethasone on Cochlear Implant Surgery
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT02497690	PHASE2	COMPLETED	Effectiveness of Therapy Via Telemedicine Following Cochlear Implants
NCT03107871	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
NCT04120116	PHASE2	COMPLETED	FX-322 in Adults With Stable Sensorineural Hearing Loss
NCT05061758	PHASE2	WITHDRAWN	A Trial of LY3056480 in Patients With SNLH
NCT07364747	PHASE2	RECRUITING	Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy