SLC19A3 solute carrier family 19 member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC19A3provided by HGNC
Official Full Name: solute carrier family 19 member 3provided by HGNC
Primary source: HGNC:HGNC:16266
See related: Ensembl:ENSG00000135917 MIM:606152; AllianceGenome:HGNC:16266
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BBGD; THMD2; THTR2; hTHTR2; thTr-2
Summary: This gene encodes a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity. Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild cognitive disability, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[provided by RefSeq, Jan 2010]
Expression: Biased expression in fat (RPKM 29.6), placenta (RPKM 8.5) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q36.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (227683763..227718028, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (228166399..228200658, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (228548479..228582744, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Alpha-mannosidosis in Tunisian consanguineous families: Potential involvement of variants in GHR and SLC19A3 genes in the variable expressivity of cognitive impairment.
Title: Alpha-mannosidosis in Tunisian consanguineous families: Potential involvement of variants in GHR and SLC19A3 genes in the variable expressivity of cognitive impairment.
Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children.
Title: Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children.
pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates.
Title: pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates.
In SLC25A19 and TPK1 defects, thiamine has also led to clinical stabilization in single cases. Moreover, thiamine supplementation leads to normal concentrations of free-thiamine in the CSF of SLC19A3 patients. [review]
Title: Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies.
Three novel mutations were detected in six patients with Biotin-thiamine responsive basal ganglia disease
Title: Are diagnostic magnetic resonance patterns life-saving in children with biotin-thiamine-responsive basal ganglia disease?
two siblings who received a refined diagnosis of BTBGD following whole-genome sequencing. Both children inherited compound heterozygous mutations from unaffected parents; a missense single-nucleotide variant (p.G23V) in the first transmembrane domain of the protein, and a 4808-bp deletion in exon 1 encompassing the 5' UTR and minimal promoter region.
Title: Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease.
Using aggregated exome sequencing data, we calculate the carrier frequency of mutations in SLC19A3 as 1 in 232 individuals in the general population, for an estimated prevalence of the disease of approximately 1 in 215,000 individuals. The disease is thus more frequent than previously recognized
Title: Biotin-thiamine responsive basal ganglia disease: Identification of a pyruvate peak on brain spectroscopy, novel mutation in SLC19A3, and calculation of prevalence based on allele frequencies from aggregated next-generation sequencing data.
Genetic variations in SLC19A3 play an important role in the pathogenesis of severe diabetic retinopathy and nephropathy and may explain why some individuals with type 1 diabetes are less prone than others to develop microvascular complications.
Title: Variation in SLC19A3 and Protection From Microvascular Damage in Type 1 Diabetes.
Genetic screening of SLC19A3 mutation is crucial to diagnosis autosomal recessive biotin-thiamine-responsive basal ganglia disease in asymptomatic relatives presenting with unexplained subacute encephalopathy and abnormal movements.
Title: A case report of biotin-thiamine-responsive basal ganglia disease in a Saudi child: Is extended genetic family study recommended?
The direct binding and activation of SLC19A3 expression by HIF-1alpha during hypoxic stress
Title: Role of HIF-1α in the hypoxia inducible expression of the thiamine transporter, SLC19A3.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Biotin-responsive basal ganglia disease MedGen: C1843807 OMIM: 607483 GeneReviews: Biotin-Thiamine-Responsive Basal Ganglia Disease	Compare labs

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of solute carrier family 19, member 3 (SLC19A3) in primary human brain microvascular endothelial cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH47615 (e-PCR)
- UniSTS:68643

G59870 (e-PCR)
- UniSTS:137153

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables thiamine transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables thiamine transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables thiamine transmembrane transporter activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in pyridoxine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in pyridoxine transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thiamine diphosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in thiamine transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in thiamine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in thiamine transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thiamine-containing compound metabolic process	TAS Traceable Author Statement more info
involved_in transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: thiamine transporter 2

Names: solute carrier family 19 (thiamine transporter), member 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016359.1 RefSeqGene

Range

5002..39267

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001371411.1 → NP_001358340.1 thiamine transporter 2 isoform 1

Status: REVIEWED

Source sequence(s)

AC064853

Consensus CDS

CCDS2468.1

UniProtKB/Swiss-Prot

Q9BZV2

UniProtKB/TrEMBL

B2R674

Related

ENSP00000258403.3, ENST00000258403.8

Conserved Domains (1) summary

pfam01770
Location:10 → 441

Folate_carrier; Reduced folate carrier
NM_001371412.1 → NP_001358341.1 thiamine transporter 2 isoform 1

Status: REVIEWED

Source sequence(s)

AC064853

Consensus CDS

CCDS2468.1

UniProtKB/Swiss-Prot

Q9BZV2

UniProtKB/TrEMBL

B2R674

Conserved Domains (1) summary

pfam01770
Location:10 → 441

Folate_carrier; Reduced folate carrier
NM_001371413.1 → NP_001358342.1 thiamine transporter 2 isoform 2

Status: REVIEWED

Source sequence(s)

AC064853, AC093762

UniProtKB/TrEMBL

B7Z761

Conserved Domains (1) summary

pfam01770
Location:47 → 437

Folate_carrier; Reduced folate carrier
NM_001371414.1 → NP_001358343.1 thiamine transporter 2 isoform 2

Status: REVIEWED

Source sequence(s)

AC064853

UniProtKB/TrEMBL

B7Z761

Conserved Domains (1) summary

pfam01770
Location:47 → 437

Folate_carrier; Reduced folate carrier
NM_025243.4 → NP_079519.1 thiamine transporter 2 isoform 1

See identical proteins and their annotated locations for NP_079519.1

Status: REVIEWED

Source sequence(s)

AC064853, AC093762, AF271633, AI056985

Consensus CDS

CCDS2468.1

UniProtKB/Swiss-Prot

Q9BZV2

UniProtKB/TrEMBL

B2R674

Related

ENSP00000495385.1, ENST00000644224.2

Conserved Domains (1) summary

pfam01770
Location:10 → 441

Folate_carrier; Reduced folate carrier