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 ... See more...

Aliases for SLC19A3 Gene

Aliases for SLC19A3 Gene

  • Solute Carrier Family 19 Member 3 2 3 4 5
  • Thiamine Transporter 2 2 3 4
  • Solute Carrier Family 19 (Thiamine Transporter), Member 3 2 3
  • ThTr-2 3 4
  • THTR2 2 3
  • Solute Carrier Family 19, Member 3 2
  • SLC19A3 5
  • THMD2 3
  • ThTr2 4
  • BBGD 3

External Ids for SLC19A3 Gene

Previous GeneCards Identifiers for SLC19A3 Gene

  • GC02M226571
  • GC02M227281
  • GC02M228513
  • GC02M228752
  • GC02M228375
  • GC02M228258
  • GC02M220392

Summaries for SLC19A3 Gene

Entrez Gene Summary for SLC19A3 Gene

  • 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]

GeneCards Summary for SLC19A3 Gene

SLC19A3 (Solute Carrier Family 19 Member 3) is a Protein Coding gene. Diseases associated with SLC19A3 include Thiamine Metabolism Dysfunction Syndrome 2 and Infantile Spasms-Psychomotor Retardation-Progressive Brain Atrophy-Basal Ganglia Disease Syndrome. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Vitamin digestion and absorption. An important paralog of this gene is SLC19A2.

UniProtKB/Swiss-Prot Summary for SLC19A3 Gene

  • Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism. Has no folate transport activity.

Gene Wiki entry for SLC19A3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SLC19A3 Gene

Genomics for SLC19A3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SLC19A3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J227715 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 621.3 +0.2 170 4.7 NFKBIZ PRDM1 SP1 CEBPB KLF9 RNF2 FOXA2 ATF3 YY1 ZBTB33 SLC19A3 lnc-C2orf83-3 lnc-C2orf83-2 SCYGR5
GH02J227671 Enhancer 0.8 FANTOM5 Ensembl dbSUPER 19.6 +45.8 45829 1.6 MAFF MAFK SLC19A3 C2orf83 CCL20 SCYGR5 lnc-C2orf83-1
GH02J227705 Enhancer 1 ENCODE dbSUPER 13 +11.0 10996 2.3 GATAD2A TFE3 RCOR2 RXRB IRF2 SP1 CEBPA SOX13 ZBTB26 FOXA2 SLC19A3 piR-48325-097 lnc-C2orf83-3 lnc-C2orf83-1 SCYGR5
GH02J227700 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 7.2 +15.2 15214 4 CREB1 GATAD2A REST FOXA1 RXRB SP1 CEBPA ATF7 ZBTB20 ETS1 CCL20 SLC19A3 piR-48325-097 lnc-C2orf83-1 lnc-C2orf83-3 SCYGR5
GH02J227674 Enhancer 0.4 FANTOM5 dbSUPER 16.2 +43.4 43421 0.3 SLC19A3 C2orf83 CCL20 SCYGR5 lnc-C2orf83-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SLC19A3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SLC19A3

Top Transcription factor binding sites by QIAGEN in the SLC19A3 gene promoter:
  • C/EBPalpha
  • CUTL1
  • E47
  • FOXD3
  • Hand1
  • HNF-3beta
  • NF-AT
  • NF-kappaB
  • NF-kappaB1
  • NF-kappaB2

Genomic Locations for SLC19A3 Gene

Genomic Locations for SLC19A3 Gene
chr2:227,683,763-227,718,030
(GRCh38/hg38)
Size:
34,268 bases
Orientation:
Minus strand
chr2:228,549,926-228,582,745
(GRCh37/hg19)
Size:
32,820 bases
Orientation:
Minus strand

Genomic View for SLC19A3 Gene

Genes around SLC19A3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC19A3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC19A3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC19A3 Gene

Proteins for SLC19A3 Gene

  • Protein details for SLC19A3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BZV2-S19A3_HUMAN
    Recommended name:
    Thiamine transporter 2
    Protein Accession:
    Q9BZV2

    Protein attributes for SLC19A3 Gene

    Size:
    496 amino acids
    Molecular mass:
    55665 Da
    Quaternary structure:
    No Data Available

neXtProt entry for SLC19A3 Gene

Post-translational modifications for SLC19A3 Gene

  • Glycosylation at Asn45 and Asn166
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SLC19A3 Gene

Domains & Families for SLC19A3 Gene

Gene Families for SLC19A3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted membrane proteins
  • Transporters

Protein Domains for SLC19A3 Gene

InterPro:
Blocks:
  • Reduced folate carrier
ProtoNet:

Suggested Antigen Peptide Sequences for SLC19A3 Gene

GenScript: Design optimal peptide antigens:
  • Solute carrier family 19 member 3 (S19A3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BZV2

UniProtKB/Swiss-Prot:

S19A3_HUMAN :
  • Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.
Family:
  • Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.
genes like me logo Genes that share domains with SLC19A3: view

Function for SLC19A3 Gene

Molecular function for SLC19A3 Gene

UniProtKB/Swiss-Prot Function:
Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism. Has no folate transport activity.

Phenotypes From GWAS Catalog for SLC19A3 Gene

Gene Ontology (GO) - Molecular Function for SLC19A3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0015234 thiamine transmembrane transporter activity IEA,ISS --
GO:0090482 vitamin transmembrane transporter activity IEA --
genes like me logo Genes that share ontologies with SLC19A3: view
genes like me logo Genes that share phenotypes with SLC19A3: view

Human Phenotype Ontology for SLC19A3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLC19A3 Gene

MGI Knock Outs for SLC19A3:

Animal Model Products

  • Taconic Biosciences Mouse Models for SLC19A3

CRISPR Products

miRNA for SLC19A3 Gene

miRTarBase miRNAs that target SLC19A3

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC19A3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SLC19A3 Gene

Localization for SLC19A3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC19A3 Gene

Membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SLC19A3 gene
Compartment Confidence
plasma membrane 4
nucleus 3
mitochondrion 2
cytosol 2
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SLC19A3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA,NAS 11136550
genes like me logo Genes that share ontologies with SLC19A3: view

Pathways & Interactions for SLC19A3 Gene

genes like me logo Genes that share pathways with SLC19A3: view

Pathways by source for SLC19A3 Gene

SIGNOR curated interactions for SLC19A3 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for SLC19A3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0015888 thiamine transport IEA --
GO:0035461 vitamin transmembrane transport IEA --
GO:0042723 thiamine-containing compound metabolic process TAS --
GO:0051180 vitamin transport IEA --
GO:0055085 transmembrane transport IBA 21873635
genes like me logo Genes that share ontologies with SLC19A3: view

Drugs & Compounds for SLC19A3 Gene

(3) Drugs for SLC19A3 Gene - From: DrugBank, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Thiamine Approved, Investigational, Vet_approved Nutra Transporter, substrate 165,165
Cysteine Approved Nutra 250
[<sup>3</sup>H]thiamine Pharma 0
genes like me logo Genes that share compounds with SLC19A3: view

Transcripts for SLC19A3 Gene

mRNA/cDNA for SLC19A3 Gene

5 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
14 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC19A3

Alternative Splicing Database (ASD) splice patterns (SP) for SLC19A3 Gene

No ASD Table

Relevant External Links for SLC19A3 Gene

GeneLoc Exon Structure for
SLC19A3

Expression for SLC19A3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SLC19A3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SLC19A3 Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x13.6), Adipose - Subcutaneous (x13.5), and Breast - Mammary Tissue (x7.7).

Protein differential expression in normal tissues from HIPED for SLC19A3 Gene

This gene is overexpressed in Liver (24.5), Blymphocyte (17.6), Spleen (6.8), and Gallbladder (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SLC19A3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SLC19A3

SOURCE GeneReport for Unigene cluster for SLC19A3 Gene:

Hs.221597

mRNA Expression by UniProt/SwissProt for SLC19A3 Gene:

Q9BZV2-S19A3_HUMAN
Tissue specificity: Widely expressed but most abundant in placenta, kidney and liver.

Evidence on tissue expression from TISSUES for SLC19A3 Gene

  • Liver(4.4)
  • Nervous system(4.4)
  • Kidney(2.3)
  • Intestine(2.2)
  • Pancreas(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC19A3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cranial nerve
  • eye
  • eyelid
  • face
  • head
  • meninges
  • mouth
  • neck
  • pharynx
Thorax:
  • chest wall
  • esophagus
  • lung
Abdomen:
  • abdominal wall
  • liver
  • stomach
Limb:
  • foot
  • lower limb
General:
  • blood
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
  • white blood cell
genes like me logo Genes that share expression patterns with SLC19A3: view

No data available for Protein tissue co-expression partners for SLC19A3 Gene

Orthologs for SLC19A3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC19A3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SLC19A3 30 31
  • 99.26 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LOC486151 30
  • 85.25 (n)
SLC19A3 31
  • 82 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia SLC19A3 30 31
  • 83.26 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Slc19a3 30 17 31
  • 75.36 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SLC19A3 31
  • 74 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Slc19a3 30
  • 73.83 (n)
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 65 (a)
OneToMany
-- 31
  • 63 (a)
OneToMany
Chicken
(Gallus gallus)
Aves SLC19A3 30
  • 64.55 (n)
-- 31
  • 62 (a)
OneToMany
-- 31
  • 61 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia SLC19A3 31
  • 61 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia MGC52872 30
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia Str.8267 30
Zebrafish
(Danio rerio)
Actinopterygii LOC557854 30
  • 55.23 (n)
slc19a3b 31
  • 45 (a)
OneToMany
slc19a3a 31
  • 43 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta CG6574 30 31 32
  • 49.31 (n)
ManyToMany
CG17036 31 32
  • 37 (a)
ManyToMany
CG14694 31 32
  • 32 (a)
ManyToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012955 30
  • 47.32 (n)
Worm
(Caenorhabditis elegans)
Secernentea folt-1 31
  • 35 (a)
ManyToMany
folt-3 31
  • 33 (a)
ManyToMany
folt-2 31
  • 33 (a)
ManyToMany
F37B4.7 32
  • 32 (a)
C06H2.4 32
  • 31 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 46 (a)
OneToMany
Species where no ortholog for SLC19A3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for SLC19A3 Gene

ENSEMBL:
Gene Tree for SLC19A3 (if available)
TreeFam:
Gene Tree for SLC19A3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SLC19A3: view image

Paralogs for SLC19A3 Gene

Paralogs for SLC19A3 Gene

(2) SIMAP similar genes for SLC19A3 Gene using alignment to 7 proteins:

  • S19A3_HUMAN
  • B8ZZ39_HUMAN
  • B8ZZW1_HUMAN
  • C9IZI1_HUMAN
  • C9J4J5_HUMAN
  • E7EM61_HUMAN
  • F5H2M8_HUMAN

Pseudogenes.org Pseudogenes for SLC19A3 Gene

genes like me logo Genes that share paralogs with SLC19A3: view

Variants for SLC19A3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SLC19A3 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
640972 Uncertain Significance: Biotin-responsive basal ganglia disease 227,696,063(-) G/A MISSENSE_VARIANT
647404 Uncertain Significance: Biotin-responsive basal ganglia disease 227,699,456(-) C/A MISSENSE_VARIANT
647857 Uncertain Significance: Biotin-responsive basal ganglia disease 227,687,440(-) T/C MISSENSE_VARIANT
650090 Uncertain Significance: Biotin-responsive basal ganglia disease 227,702,315(-) C/T MISSENSE_VARIANT
652148 Uncertain Significance: Biotin-responsive basal ganglia disease 227,687,437(-) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for SLC19A3 Gene

Structural Variations from Database of Genomic Variants (DGV) for SLC19A3 Gene

Variant ID Type Subtype PubMed ID
dgv7321n54 CNV gain 21841781
dgv7322n54 CNV gain 21841781
esv2721563 CNV deletion 23290073
nsv1000263 CNV gain 25217958
nsv1009159 CNV loss 25217958
nsv10221 CNV loss 18304495
nsv520733 CNV gain 19592680
nsv834561 CNV gain 17160897

Variation tolerance for SLC19A3 Gene

Residual Variation Intolerance Score: 81.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.60; 56.34% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SLC19A3 Gene

Human Gene Mutation Database (HGMD)
SLC19A3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC19A3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC19A3 Gene

Disorders for SLC19A3 Gene

MalaCards: The human disease database

(21) MalaCards diseases for SLC19A3 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
thiamine metabolism dysfunction syndrome 2
  • thmd2
infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome
leigh syndrome with leukodystrophy
  • infantile subacute necrotizing encephalopathy with leukodystrophy
basal ganglia disease
  • basal ganglia diseases
biotin-thiamine-responsive basal ganglia disease
  • thiamine metabolism dysfunction syndrome 2
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

S19A3_HUMAN
  • Thiamine metabolism dysfunction syndrome 2, biotin- or thiamine-responsive type (THMD2) [MIM:607483]: An autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia. {ECO:0000269 PubMed:15871139}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SLC19A3

genes like me logo Genes that share disorders with SLC19A3: view

No data available for Genatlas for SLC19A3 Gene

Publications for SLC19A3 Gene

  1. Identification and characterization of the human and mouse SLC19A3 gene: a novel member of the reduced folate family of micronutrient transporter genes. (PMID: 11136550) Eudy JD … Finnell RH (Molecular genetics and metabolism 2000) 2 3 4 23
  2. Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3. (PMID: 15871139) Zeng WQ … Gusella JF (American journal of human genetics 2005) 2 3 4
  3. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4
  4. Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood. (PMID: 15623830) Vlasova TI … Mock DM (The Journal of nutrition 2005) 3 23
  5. Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms. (PMID: 16055442) Nabokina SM … Said HM (The Journal of biological chemistry 2005) 3 23

Products for SLC19A3 Gene

Sources for SLC19A3 Gene