SLC52A3

solute carrier family 52 member 3, the group of Solute carrier family 52

Basic information

Region (hg38): 20:760080-776015

Previous symbols: [ "C20orf54" ]

Links

ENSG00000101276

∙ NCBI:113278 ∙ OMIM:613350 ∙ HGNC:16187 ∙ Uniprot:Q9NQ40 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Brown-Vialetto-van Laere syndrome 1 (Definitive), mode of inheritance: AR
Brown-Vialetto-van Laere syndrome 1 (Strong), mode of inheritance: AR
Brown-Vialetto-van Laere syndrome 1 (Strong), mode of inheritance: AR
progressive bulbar palsy (Moderate), mode of inheritance: AR
Brown-Vialetto-van Laere syndrome 1 (Definitive), mode of inheritance: AR
Brown-Vialetto-van Laere syndrome 1 (Strong), mode of inheritance: AR
Brown-Vialetto-van Laere syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brown-Vialetto-Van Laere syndrome 1; Fazio-Londe disease	AR	Biochemical	Individuals typically manifest with progressive neurological dysfunction, including hearing loss, and there is evidence that high-dose riboflavin therapy may be beneficial in some individuals	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	13900073; 5969547; 5563586; 7425580; 7229669; 2325091; 16122634; 20206331; 20920669; 21110228; 22098162; 22740598; 22633641; 22211384; 23107375

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC52A3 gene.

Brown-Vialetto-van_Laere_syndrome_1 (386 variants)
Inborn_genetic_diseases (116 variants)
not_provided (80 variants)
not_specified (24 variants)
SLC52A3-related_disorder (17 variants)
Progressive_bulbar_palsy_of_childhood (13 variants)
Auditory_neuropathy (2 variants)
Madras_motor_neuron_disease (1 variants)
Monogenic_hearing_loss (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC52A3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000033409.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				136 clinvar	3 clinvar	139
missense	3 clinvar	15 clinvar	207 clinvar	12 clinvar		237
nonsense	9 clinvar	1 clinvar	3 clinvar			13
start loss			1			1
frameshift	3 clinvar	5 clinvar	1 clinvar			9
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	16	21	213	148	3

Highest pathogenic variant AF is 0.00012581049

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC52A3	protein_coding	protein_coding	ENST00000217254	4	8408

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0193	0.964	125731	0	15	125746	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	214	272	0.787	0.0000165	2969
Missense in Polyphen		44	73.358	0.5998		863
Synonymous	-0.517	130	123	1.06	0.00000798	1025
Loss of Function	2.08	5	13.1	0.380	5.73e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000931	0.0000924
European (Non-Finnish)	0.000110	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transporter for riboflavin, which must be obtained as a nutrient via intestinal absorption. Riboflavin transport is Na(+)- independent at low pH but significantly reduced by Na(+) depletion under neutral pH conditions. Activity is strongly inhibited by riboflavin analogs, such as lumiflavin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), by methylene blue, and to a lesser extent by amiloride. {ECO:0000269|PubMed:20463145, ECO:0000269|PubMed:22273710, ECO:0000269|PubMed:24264046, ECO:0000269|PubMed:27702554}.;
Disease: DISEASE: Fazio-Londe disease (FALOND) [MIM:211500]: A rare neurological disease characterized by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. It may present in childhood with severe neurological deterioration with hypotonia, respiratory insufficiency leading to premature death, or later in life with bulbar weakness which progresses to involve motor neurons throughout the neuroaxis. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles. {ECO:0000269|PubMed:21110228}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Vitamin digestion and absorption - Homo sapiens (human);Metabolism;Vitamin B2 (riboflavin) metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

pRec: 0.105

Intolerance Scores

loftool
rvis_EVS: 0.09
rvis_percentile_EVS: 60.65

Haploinsufficiency Scores

pHI: 0.148
hipred: N
hipred_score: 0.264
ghis: 0.474

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc52a3
Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); renal/urinary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: riboflavin metabolic process;sensory perception of sound;riboflavin transport;cellular response to heat
Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;apical plasma membrane;nuclear membrane
Molecular function: riboflavin transmembrane transporter activity