Skip to content
GenoLensGenoLens

SLC46A1

Chr 17q11.2

solute carrier family 46 member 1

Aliases:
HCP1, MGC9564, PCFT, HsPCFT, hPCFT
MANE:
ENST00000612814.5
OMIM: 611672 ↗NCBI: 113235 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Cerebral folate deficiency

    BIALLELIC, autosomal or pseudoautosomal

  • COVID-19 research

    BIALLELIC, autosomal or pseudoautosomal

  • Cytopenias and congenital anaemias

    BIALLELIC, autosomal or pseudoautosomal

  • DDG2P

    BIALLELIC, autosomal or pseudoautosomal

  • Intellectual disability

    BIALLELIC, autosomal or pseudoautosomal

  • Likely inborn error of metabolism

    BIALLELIC, autosomal or pseudoautosomal

  • Primary immunodeficiency or monogenic inflammatory bowel disease

    BIALLELIC, autosomal or pseudoautosomal

  • Undiagnosed metabolic disorders

    BIALLELIC, autosomal or pseudoautosomal

+6 more panels — install the extension to see the full list inline on any page.

Disease associations (Open Targets)

  • hereditary folate malabsorption

    0.84

  • anemia (phenotype)

    0.42

  • anemia

    0.42

  • Pancytopenia

    0.42

  • hereditary disease

    0.41

  • neurodegenerative disease

    0.18

  • age-related macular degeneration

    0.13

  • COVID-19

    0.13

  • Intellectual disability

    0.11

  • atrophic macular degeneration

    0.09

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Proton-coupled folate transporter

Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:19762432, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:31792273, PubMed:32893190, PubMed:34619546). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:32893190). Functions at acidic pH via alternate outward- and inward-open conformation states (PubMed:32893190, PubMed:34040256). Protonation of residues in the outward open state primes the protein for transport (PubMed:34040256). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (PubMed:34040256). Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases (PubMed:18524888, PubMed:19762432, PubMed:22345511, PubMed:25608532, PubMed:28802835, PubMed:29326243, PubMed:34040256, PubMed:34619546). Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes (PubMed:19074442). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (PubMed:17156779). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (PubMed:32621820). Hence, participates in the trafficking of heme and increases intracellular iron content (PubMed:32621820)

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.