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Aliases for SLC46A1 Gene

Aliases for SLC46A1 Gene

  • Solute Carrier Family 46 Member 1 2 3 4 5
  • Heme Carrier Protein 1 2 3 4
  • Solute Carrier Family 46 (Folate Transporter), Member 1 2 3
  • Proton-Coupled Folate Transporter 2 3
  • HCP1 3 4
  • PCFT 3 4
  • G21 3 4
  • Solute Carrier Family 46, Member 1 2
  • PCFT/HCP1 4

External Ids for SLC46A1 Gene

Previous GeneCards Identifiers for SLC46A1 Gene

  • GC17M023753
  • GC17M026721
  • GC17M022930
  • GC17M028397
  • GC17M028477
  • GC17M028560
  • GC17M028626
  • GC17M028711
  • GC17M028807

Summaries for SLC46A1 Gene

Entrez Gene Summary for SLC46A1 Gene

  • This gene encodes a transmembrane proton-coupled folate transporter protein that facilitates the movement of folate and antifolate substrates across cell membranes, optimally in acidic pH environments. This protein is also expressed in the brain and choroid plexus where it transports folates into the central nervous system. This protein further functions as a heme transporter in duodenal enterocytes, and potentially in other tissues like liver and kidney. Its localization to the apical membrane or cytoplasm of intestinal cells is modulated by dietary iron levels. Mutations in this gene are associated with autosomal recessive hereditary folate malabsorption disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]

GeneCards Summary for SLC46A1 Gene

SLC46A1 (Solute Carrier Family 46 Member 1) is a Protein Coding gene. Diseases associated with SLC46A1 include Folate Malabsorption, Hereditary and Folic Acid Deficiency Anemia. Among its related pathways are Metabolism and Vitamin digestion and absorption. GO annotations related to this gene include transmembrane transporter activity and heme transporter activity. An important paralog of this gene is SLC46A3.

UniProtKB/Swiss-Prot for SLC46A1 Gene

  • Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. The iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron. Shows a higher affinity for folate than heme.

Gene Wiki entry for SLC46A1 Gene

Additional gene information for SLC46A1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC46A1 Gene

Genomics for SLC46A1 Gene

Regulatory Elements for SLC46A1 Gene

Enhancers for SLC46A1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH17H028355 1.1 ENCODE 11.2 +49.9 49912 2.8 PKNOX1 ARID4B SIN3A DMAP1 YY1 ZNF207 ZNF143 SP3 ZHX2 MXD4 SUPT6H SARM1 ITM2BP1 PHF12 TMEM199 SLC46A1 NUFIP2 UNC119 PIGS SGK494
GH17H028380 1 ENCODE 12 +26.9 26851 0.2 PKNOX1 FOXA2 ATF1 SIN3A FEZF1 BRCA1 ZNF207 FOS ATF7 DEK ITM2BP1 ENSG00000264577 SUPT6H NUFIP2 ENSG00000265205 ENSG00000265908 PHF12 SLC46A1 RPL23A SDF2
GH17H028317 1.1 ENCODE 10.6 +87.8 87829 3.7 HDGF MLX ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF143 FOS LOC101927018 TMEM199 SUPT6H ENSG00000264577 TMEM97 NUFIP2 SLC46A1 ENSG00000265908 PHF12 VTN
GH17H028323 1 Ensembl ENCODE 10.6 +81.8 81784 2.9 PKNOX1 NFIB SIN3A CEBPG YY1 CTBP1 GATA3 POLR2A NFE2 RCOR1 SLC46A1 VTN TRAF4 GC17M028919 TMEM97
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SLC46A1 on UCSC Golden Path with GeneCards custom track

Promoters for SLC46A1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000092717 1197 1201 SIN3A DMAP1 ZNF2 YY1 GLIS2 ZNF207 KLF7 ZNF548 SP3 SP5

Genomic Locations for SLC46A1 Gene

Genomic Locations for SLC46A1 Gene
12,556 bases
Minus strand

Genomic View for SLC46A1 Gene

Genes around SLC46A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC46A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC46A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC46A1 Gene

Proteins for SLC46A1 Gene

  • Protein details for SLC46A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Proton-coupled folate transporter
    Protein Accession:
    Secondary Accessions:
    • Q1HE20
    • Q86T92
    • Q8TEG3
    • Q96FL0

    Protein attributes for SLC46A1 Gene

    459 amino acids
    Molecular mass:
    49771 Da
    Quaternary structure:
    • Monomer.

    Alternative splice isoforms for SLC46A1 Gene


neXtProt entry for SLC46A1 Gene

Post-translational modifications for SLC46A1 Gene

  • Ubiquitination at isoforms=2262
  • Glycosylation at Asn58 and Asn68
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SLC46A1 Gene

Domains & Families for SLC46A1 Gene

Gene Families for SLC46A1 Gene

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

Protein Domains for SLC46A1 Gene

Suggested Antigen Peptide Sequences for SLC46A1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the major facilitator superfamily. SLC46A family.
  • Belongs to the major facilitator superfamily. SLC46A family.
genes like me logo Genes that share domains with SLC46A1: view

Function for SLC46A1 Gene

Molecular function for SLC46A1 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.3 uM for folic acid (at pH 5.5) {ECO:0000269 PubMed:17129779, ECO:0000269 PubMed:17475902}; KM=1.5 uM for folic acid (at pH 6.0) {ECO:0000269 PubMed:17129779, ECO:0000269 PubMed:17475902}; KM=2.7 uM for folic acid (at pH 6.5) {ECO:0000269 PubMed:17129779, ECO:0000269 PubMed:17475902}; KM=6.0 uM for folic acid (at pH 7.0) {ECO:0000269 PubMed:17129779, ECO:0000269 PubMed:17475902}; KM=56.2 uM for folic acid (at pH 7.5) {ECO:0000269 PubMed:17129779, ECO:0000269 PubMed:17475902}; pH dependence: Optimum pH is 4.0-5.5. Activity decreases above pH 5.5 and reaches negligible levels at neutral pH and above. {ECO:0000269 PubMed:17129779, ECO:0000269 PubMed:17475902};
UniProtKB/Swiss-Prot Function:
Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. The iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron. Shows a higher affinity for folate than heme.

Phenotypes From GWAS Catalog for SLC46A1 Gene

Gene Ontology (GO) - Molecular Function for SLC46A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005542 folic acid binding IEA --
GO:0008517 folic acid transporter activity TAS --
GO:0015078 hydrogen ion transmembrane transporter activity IDA 17129779
GO:0015232 heme transporter activity TAS --
GO:0015350 methotrexate transporter activity IC 19762432
genes like me logo Genes that share ontologies with SLC46A1: view
genes like me logo Genes that share phenotypes with SLC46A1: view

Human Phenotype Ontology for SLC46A1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLC46A1 Gene

MGI Knock Outs for SLC46A1:

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SLC46A1 Gene

Localization for SLC46A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC46A1 Gene

Apical cell membrane; Multi-pass membrane protein. Cytoplasm. Note=Localizes to the apical membrane of intestinal cells in iron-deficient cells, while it resides in the cytoplasm in iron-replete cells. {ECO:0000250}.

Subcellular locations from

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 SLC46A1 gene
Compartment Confidence
plasma membrane 5
cytosol 3
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SLC46A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm ISS --
GO:0005886 plasma membrane TAS,IDA --
GO:0009986 cell surface IDA 19581412
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SLC46A1: view

Pathways & Interactions for SLC46A1 Gene

genes like me logo Genes that share pathways with SLC46A1: view

Pathways by source for SLC46A1 Gene

Interacting Proteins for SLC46A1 Gene

Gene Ontology (GO) - Biological Process for SLC46A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IEA --
GO:0006879 cellular iron ion homeostasis TAS --
GO:0015884 folic acid transport IMP 17129779
GO:0015886 heme transport IEA --
GO:0046655 folic acid metabolic process TAS --
genes like me logo Genes that share ontologies with SLC46A1: view

No data available for SIGNOR curated interactions for SLC46A1 Gene

Drugs & Compounds for SLC46A1 Gene

(12) Drugs for SLC46A1 Gene - From: DrugBank, DGIdb, IUPHAR, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sulfasalazine Approved Pharma Inhibition, Inhibitor, inhibitor, Transporter NF-κB activation inhibitor 62
Methotrexate Approved Pharma Transporter, substrate, inhibitor Folate antagonist,inhibits DFHR 1576
Folic Acid Approved, Vet_approved Nutra Transporter, substrate 4513
Indomethacin Approved, Investigational Pharma Partial agonist, Agonist, inhibitor Cox inhibitor 118
Levomefolic acid Approved Pharma Transporter, substrate Active form of folic acid 0

(1) Additional Compounds for SLC46A1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
genes like me logo Genes that share compounds with SLC46A1: view

Transcripts for SLC46A1 Gene

Unigene Clusters for SLC46A1 Gene

Solute carrier family 46 (folate transporter), member 1:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SLC46A1 Gene

No ASD Table

Relevant External Links for SLC46A1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for SLC46A1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SLC46A1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SLC46A1 Gene

This gene is overexpressed in Adrenal Gland (x6.7) and Liver (x5.3).

Protein differential expression in normal tissues from HIPED for SLC46A1 Gene

This gene is overexpressed in Fetal gut (15.0), Liver (8.2), Spinal cord (7.6), Placenta (6.6), and Rectum (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SLC46A1 Gene

Protein tissue co-expression partners for SLC46A1 Gene

NURSA nuclear receptor signaling pathways regulating expression of SLC46A1 Gene:


SOURCE GeneReport for Unigene cluster for SLC46A1 Gene:


mRNA Expression by UniProt/SwissProt for SLC46A1 Gene:

Tissue specificity: Expressed in kidney, liver, placenta, small intestine, spleen, retina and retinal pigment epithelium. Lower levels found in colon and testis. Very low levels in brain, lung, stomach, heart and muscle. In intestine, expressed in duodenum with lower levels in jejunum, ileum, cecum, rectum and segments of the colon.

Evidence on tissue expression from TISSUES for SLC46A1 Gene

  • Nervous system(4.7)
  • Eye(4.3)
  • Liver(4.3)
  • Spleen(4.2)
  • Intestine(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC46A1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeletal muscle
Head and neck:
  • brain
  • cerebellum
  • face
  • head
  • lip
  • mouth
  • tongue
  • diaphragm
  • esophagus
  • lung
  • intestine
  • large intestine
  • small intestine
  • stomach
  • arm
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • toe
  • upper limb
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with SLC46A1: view

Orthologs for SLC46A1 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC46A1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia SLC46A1 34
  • 100 (a)
(Canis familiaris)
Mammalia SLC46A1 33 34
  • 87.51 (n)
(Rattus norvegicus)
Mammalia Slc46a1 33
  • 84.43 (n)
(Bos Taurus)
Mammalia SLC46A1 33 34
  • 84.31 (n)
(Mus musculus)
Mammalia Slc46a1 33 16 34
  • 83.95 (n)
(Ornithorhynchus anatinus)
Mammalia SLC46A1 34
  • 67 (a)
(Monodelphis domestica)
Mammalia SLC46A1 34
  • 65 (a)
(Gallus gallus)
Aves SLC46A1 33 34
  • 64.75 (n)
(Anolis carolinensis)
Reptilia SLC46A1 34
  • 48 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia slc46a1 33
  • 62.75 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.15282 33
(Danio rerio)
Actinopterygii slc46a1 33 34
  • 59.7 (n)
zgc56400 33
fruit fly
(Drosophila melanogaster)
Insecta CG30344 34
  • 20 (a)
CG30345 34
  • 19 (a)
CG8046 34
  • 18 (a)
CG15553 34
  • 17 (a)
CG42514 34
  • 17 (a)
CG8008 34
  • 17 (a)
CG15890 34
  • 15 (a)
CG31321 34
  • 13 (a)
(Caenorhabditis elegans)
Secernentea Y4C6B.5 33 34
  • 39.04 (n)
Y43F8A.5 34
  • 18 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 31 (a)
Species where no ortholog for SLC46A1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • 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 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 SLC46A1 Gene

Gene Tree for SLC46A1 (if available)
Gene Tree for SLC46A1 (if available)

Paralogs for SLC46A1 Gene

Paralogs for SLC46A1 Gene

(2) SIMAP similar genes for SLC46A1 Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with SLC46A1: view

Variants for SLC46A1 Gene

Sequence variations from dbSNP and Humsavar for SLC46A1 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
rs281875208 Pathogenic, Hereditary folate malabsorption (HFM) [MIM:229050] 28,404,693(-) GGTAG(A/C)TGAGA reference, missense
rs281875209 Pathogenic, Hereditary folate malabsorption (HFM) [MIM:229050] 28,404,685(-) AGATC(A/C/G)GCCTG reference, missense
rs281875210 Pathogenic, Hereditary folate malabsorption (HFM) [MIM:229050] 28,405,231(-) TCGGC(G/T)ACTTC reference, missense
rs281875211 Pathogenic, Hereditary folate malabsorption (HFM) [MIM:229050] 28,402,276(-) CATCC(A/G)GGCTA intron-variant, reference, missense
rs80338770 Pathogenic, Hereditary folate malabsorption (HFM) [MIM:229050], Hereditary folate malabsorption (HFM) [MIM:229050] 28,405,360(-) TGGGC(A/C/T)GCCGC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for SLC46A1 Gene

Variant ID Type Subtype PubMed ID
nsv574653 CNV gain 21841781
nsv1062056 CNV gain 25217958
nsv1056839 CNV gain 25217958

Variation tolerance for SLC46A1 Gene

Gene Damage Index Score: 1.55; 30.09% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SLC46A1 Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC46A1 Gene

Disorders for SLC46A1 Gene

MalaCards: The human disease database

(3) MalaCards diseases for SLC46A1 Gene - From: HGMD, OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, and DISEASES

Disorder Aliases PubMed IDs
folate malabsorption, hereditary
  • hereditary folate malabsorption
folic acid deficiency anemia
  • folate deficiency anemia
thiamine metabolism dysfunction syndrome 2
  • biotin-responsive basal ganglia disease
- elite association - COSMIC cancer census association via MalaCards


  • Hereditary folate malabsorption (HFM) [MIM:229050]: Rare autosomal recessive disorder characterized by impaired intestinal folate absorption with folate deficiency resulting in anemia, hypoimmunoglobulinemia with recurrent infections, and recurrent or chronic diarrhea. In many patients, neurological abnormalities such as seizures or mental retardation become apparent during early childhood, attributed to impaired transport of folates into the central nervous system. When diagnosed early, the disorder can be treated by administration of folate. If untreated, it can be fatal and, if treatment is delayed, the neurological defects can become permanent. {ECO:0000269 PubMed:17129779, ECO:0000269 PubMed:17446347, ECO:0000269 PubMed:18559978, ECO:0000269 PubMed:20686069, ECO:0000269 PubMed:20805364, ECO:0000269 PubMed:21333572}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for SLC46A1

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with SLC46A1: view

No data available for Genatlas for SLC46A1 Gene

Publications for SLC46A1 Gene

  1. Identification of an intestinal heme transporter. (PMID: 16143108) Shayeghi M … McKie AT (Cell 2005) 2 3 4 22 60
  2. Heme carrier protein 1 (HCP1) genetic variants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study participants. (PMID: 19176287) Wang X … Eckfeldt JH (Blood cells, molecules & diseases 2009) 3 22 45 60
  3. Heme carrier protein 1 (HCP1) expression and functional analysis in the retina and retinal pigment epithelium. (PMID: 17335806) Sharma S … Della NG (Experimental cell research 2007) 3 4 22 60
  4. Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. (PMID: 17475902) Nakai Y … Yuasa H (The Journal of pharmacology and experimental therapeutics 2007) 3 4 25 60
  5. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. (PMID: 17129779) Qiu A … Goldman ID (Cell 2006) 2 3 4 60

Products for SLC46A1 Gene

Sources for SLC46A1 Gene

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