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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]
SLC46A1 (Solute Carrier Family 46 Member 1) is a Protein Coding gene. Diseases associated with SLC46A1 include Folate Malabsorption, Hereditary and Vitamin Metabolic Disorder. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Insulin receptor recycling. Gene Ontology (GO) annotations related to this gene include transmembrane transporter activity and heme transporter activity. An important paralog of this gene is SLC46A3.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005542 | folic acid binding | IEA | -- |
GO:0008517 | folic acid transmembrane transporter activity | TAS | -- |
GO:0015078 | proton transmembrane transporter activity | IDA | 17129779 |
GO:0015232 | heme transporter activity | TAS | -- |
GO:0015350 | methotrexate transmembrane transporter activity | IC | 19762432 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | ISS | -- |
GO:0005886 | plasma membrane | TAS | -- |
GO:0009986 | cell surface | HDA | 19581412 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Metabolism of water-soluble vitamins and cofactors | ||
2 | Antifolate resistance | ||
3 | Mineral absorption | ||
4 | Vitamin digestion and absorption | ||
5 | Methotrexate Pathway, Pharmacokinetics |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
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 | -- |
GO:0051958 | methotrexate transport | IMP | 17129779 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sulfasalazine | Approved | Pharma | Inhibitor, Inhibition, Transporter | NF-κB activation inhibitor | 89 | |
Methotrexate | Approved | Pharma | Transporter, substrate, inhibitor | Folate antagonist,inhibits DFHR | 1874 | |
Folic acid | Approved, Vet_approved | Nutra | Transporter, substrate | 4954 | ||
Indomethacin | Approved, Investigational | Pharma | Inhibitor, Inhibition | Cox inhibitor | 153 | |
Levomefolic acid | Approved, Investigational | Pharma | Transporter, substrate | 0 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | SLC46A1 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | SLC46A1 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Slc46a1 30 |
|
||
Cow (Bos Taurus) |
Mammalia | SLC46A1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Slc46a1 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | SLC46A1 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | SLC46A1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | SLC46A1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | SLC46A1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | slc46a1 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.15282 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | slc46a1 30 31 |
|
OneToOne | |
zgc56400 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | CG30344 31 |
|
ManyToMany | |
CG30345 31 |
|
ManyToMany | |||
CG8046 31 |
|
ManyToMany | |||
CG42514 31 |
|
ManyToMany | |||
CG15553 31 |
|
ManyToMany | |||
CG8008 31 |
|
ManyToMany | |||
CG15890 31 |
|
ManyToMany | |||
CG31321 31 |
|
ManyToMany | |||
Worm (Caenorhabditis elegans) |
Secernentea | Y4C6B.5 30 31 |
|
ManyToMany | |
Y43F8A.5 31 |
|
ManyToMany | |||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 17 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
871001 | Uncertain Significance: not provided | 28,405,132(-) |
C/G NM_080669.6(SLC46A1):c.565G>C (p.Gly189Arg) |
MISSENSE | |
888567 | Benign: Congenital defect of folate absorption | 28,395,072(-) |
G/A NM_080669.6(SLC46A1):c.*4584C>T |
THREE_PRIME_UTR_VARIANT,INTRON | |
888568 | Uncertain Significance: Congenital defect of folate absorption | 28,395,238(-) |
G/A NM_080669.6(SLC46A1):c.*4418C>T |
THREE_PRIME_UTR_VARIANT,INTRON | |
888569 | Uncertain Significance: Congenital defect of folate absorption | 28,395,472(-) |
A/C NM_080669.6(SLC46A1):c.*4184T>G |
THREE_PRIME_UTR_VARIANT,INTRON | |
888617 | Likely Benign: Congenital defect of folate absorption | 28,396,536(-) |
T/C NM_080669.6(SLC46A1):c.*3120A>G |
THREE_PRIME_UTR |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
nsv1056839 | CNV | gain | 25217958 |
nsv1062056 | CNV | gain | 25217958 |
nsv574653 | CNV | gain | 21841781 |
Disorder | Aliases | PubMed IDs |
---|---|---|
folate malabsorption, hereditary |
|
|
vitamin metabolic disorder |
|
|
folic acid deficiency anemia |
|
|
thiamine metabolism dysfunction syndrome 2 |
|
|
neural tube defects |
|
|