SLCtables

SLC46A1

Protein name: PCFT Aliases: HCP1 Substrates: Reduced folates, folic acid, antifolates Transport type: Cotransporter / proton-symporter Tissue and cellular expression: small intestine, choroid plexus, kidney (proximal tubule), liver (sinusoidal), placenta Subcellular expression: apical (small intestine, kidney), basolateral (choroid plexus), sinusoidal (liver) Disease: Hereditary folate malabsorption [OMIM: 229050] Locus: 17q11.2 Sequence ID: NP_001229295.1, NM_001242366.1 NP_542400.2, NM_080669.4 Gene ID: 113235 Splice variants: N/D

PCFT_HUMAN (UniProt)

Gene names: SLC46A1, HCP1, PCFT
Protein names and data: PCFT_HUMAN, Full=Proton-coupled folate transporter, Full=G21;Full=Heme carrier protein 1;Full=PCFT/HCP1;Full=Solute carrier family 46 member 1; Length: 459 a.a., Mass: 49771 Da,
fasta formatted sequence
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
Disease: (OMIM: 229050 611672) Defects in SLC46A1 are the cause of hereditary folate malabsorption (HFM) [MIM:229050]. HFM is a 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
Cellular location: Apical cell membrane; Multi-pass membrane protein. Cytoplasm (By similarity). Note=Localizes to the apical membrane of intestinal cells in iron-deficient cells, while it resides in the cytoplasm in iron-replete cells (By similarity)
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

Database cross-references

UniProt: Q96NT5
NextBio: 78800
OMIM: 229050 611672
Ensembl: ENST00000440501
GeneCard: GC17M028626
TCDB: 2.A.1.50.1
PharmGenUCSF: SLC46A1
Guide to Pharmacology: SLC46A1 (1213)
SLC46 family of folate transporters (1213)
HGNC: HGNC:30521

Genetic variants

See also Ensembl:ENST00000440501

113 - 113 R -> C (in HFM; loss-of-function mutation; targeted to the plasma membrane but has significantly impaired folate transport activity; dbSNP:rs80338770). VAR_058210 80338770
113 - 113 R -> S (in HFM; abolishes folate uptake). VAR_032825
147 - 147 G -> R (in HFM; reduces folate uptake to 13% of normal levels; dbSNP:rs80338771). VAR_032826 80338771
156 - 156 D -> Y (in HFM; loss of function measured as methotrexate uptake). VAR_067960
295 - 295 T -> A (in dbSNP:rs34552966). VAR_050302 34552966
318 - 318 S -> R (in HFM; abolishes folate uptake; dbSNP:rs80338772). VAR_032827 80338772
335 - 335 A -> D (in HFM; loss of function measured as methotrexate uptake). VAR_067961
338 - 338 G -> R (in HFM; loss of function measured as methotrexate uptake). VAR_067962
376 - 376 R -> Q (in HFM; abolishes folate uptake). VAR_067963
376 - 376 R -> W (in HFM; abolishes folate uptake; dbSNP:rs80338773). VAR_032828 80338773
425 - 425 P -> R (in HFM; reduces folate uptake to 3.5% of normal levels; dbSNP:rs80338774). VAR_032829 80338774