Homo sapiens gene SLC46A1, encoding solute carrier family 46 (folate transporter), member 1.
SUMMARY back to top
RefSeq summary
[SLC46A1] 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 transmembrane 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 cause the autosomal recessive hereditary folate malabsorption (HFM) disease. HFM is characterized by folate deficiency due to reduced intestinal folate absorption and subsequent anemia, hypoimmunoglobulinemia, and recurrent infections. [provided by RefSeq].

RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 6 spliced variants.

AceView synopsis, each blue text links to tables and details
Expression: According to AceView, this gene is expressed at high level, 1.4 times the average gene in this release. The sequence of this gene is defined by 167 GenBank accessions from 149 cDNA clones, some from prostate (seen 13 times), brain (12), eye (7), lung (7), spleen (7), pancreas (6), synovial membrane tissue from rheumatioidarthritis (5) and 72 other tissues. We annotate structural defects or features in 2 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 10 distinct gt-ag introns. Transcription produces 8 different mRNAs, 6 alternatively spliced variants and 2 unspliced forms. There are 4 probable alternative promotors, 2 non overlapping alternative last exons and 4 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 4 cassette exons, overlapping exons with different boundaries. 4594 bp of this gene are antisense to spliced gene TMEM199andSARM1.aAug10, 464 to keyror, raising the possibility of regulated alternate expression.
Function: There are 23 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (OMIM: Folate malabsorption, hereditary; Other sources: Malabsorption Syndromes) and proposed to participate in processes (folic acid transport, transmembrane transport). Proteins are expected to have molecular functions (folic acid transporter activity, folic acid binding, heme transporter activity) and to localize in various compartments (apical plasma membrane, cytoplasm, integral to membrane).
Protein coding potential: 6 spliced mRNAs putatively encode good proteins, altogether 6 different isoforms (4 complete, 2 COOH complete), some containing Major Facilitator Superfamily domain [Pfam], some transmembrane domains [Psort2]. The remaining 2 mRNA variants (2 unspliced; 1 partial) appear not to encode good proteins. Finally proteins from this gene may be modulated by phosphorylation, as detailed at PhosphoSite.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome 17, links to other databases and other names
Map: This gene SLC46A1 maps on chromosome 17, at 17q11.2 according to Entrez Gene. In AceView, it covers 12.56 kb, from 26734215 to 26721658 (NCBI 37, August 2010), on the reverse strand.
Links to: manual annotations from OMIM_229050, PhosphoSite, the SNP view, gene overviews from Entrez Gene 113235, GeneCards, expression data from ECgene, UniGene, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here.
Other names: The gene is also known as SLC46A1, HCP1, PCFT, MGC9564 or FLJ39875, LOC113235. It has been described as proton-coupled folate transporter, G21, PCFT/HCP1, heme carrier protein 1, solute carrier family 46 member 1.
Closest AceView homologs in other species ?
The closest mouse gene, according to BlastP, is the AceView gene Slc46a1 (e=5 10-14).
The closest C.elegans gene, according to BlastP, is the AceView/WormGene 4G89 (e=10-04)
RNA_seq discoveries back to top
Expression/conservation in primates tissues evaluated by cross-mapping to human. back to top
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: Pig-Tailed Macaque, JMI Japanese Macaque, RMI Rhesus Macaque Indian, RMC Rhesus Macaque Chinese, CMM Cynomolgus Macaque Mauritian, CMC Cynomolgus Macaque Chinese, BAB Olive Baboon, SMY Sooty Mangabey); New World monkeys (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue) and for this gene (green), in Magic index = log2(1000 sFPKM).
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC, by tissue or by species. Tracks may be slow to load; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!.
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the Flash version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
Downstream sequence
aAug10 6430 bp 458 aa 5051 bp 2kb 11510 bp 1kb
bAug10 1419 bp 421 aa 151 bp 2kb 1837 bp 1kb
cAug10 5303 bp 418 aa 38 bp 4008 bp 2kb including Promoter 10467 bp 1kb
dAug10 1970 bp 341 aa 746 bp 198 bp 81 bp 2kb possibly including promoter 7851 bp 1kb
eAug10 596 bp 111 aa 33 bp 227 bp 2kb including Promoter 1508 bp 1kb
fAug10 565 bp 96 aa 116 bp 158 bp 2kb including Promoter 1553 bp 1kb
gAug10-unspliced 1074 bp 72 aa 473 bp 382 bp 2kb including Promoter 1074 bp 1kb
hAug10-unspliced 701 bp 78 aa 463 bp 2kb 701 bp 1kb

Gene neighbors and Navigator on chromosome 17q11.2 back to top
ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications        
Annotated mRNA diagrams back to top
Bibliography:               23 articles in PubMed back to top
? Gene Summary Gene on genome mRNA:.a, .b, .c, .d, .e, .f, .g-u, .h-u Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DC

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

If you know more about this gene, or found errors, please share your knowledge. Thank you !