Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption

Cell. 2006 Dec 1;127(5):917-28. doi: 10.1016/j.cell.2006.09.041.


Folates are essential nutrients that are required for one-carbon biosynthetic and epigenetic processes. While folates are absorbed in the acidic milieu of the upper small intestine, the underlying absorption mechanism has not been defined. We now report the identification of a human proton-coupled, high-affinity folate transporter that recapitulates properties of folate transport and absorption in intestine and in various cell types at low pH. We demonstrate that a loss-of-function mutation in this gene is the molecular basis for hereditary folate malabsorption in a family with this disease. This transporter was previously reported to be a lower-affinity, pH-independent heme carrier protein, HCP1. However, the current study establishes that a major function of this gene product is proton-coupled folate transport required for folate homeostasis in man, and we have thus amended the name to PCFT/HCP1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport
  • Caco-2 Cells
  • Cell Line, Tumor
  • Electrophysiology
  • Folic Acid / chemistry
  • Folic Acid / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Intestinal Mucosa / metabolism*
  • Kinetics
  • Malabsorption Syndromes / genetics*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Oocytes
  • Pedigree
  • Proton-Coupled Folate Transporter
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Substrate Specificity
  • Xenopus


  • Membrane Transport Proteins
  • Proton-Coupled Folate Transporter
  • RNA, Messenger
  • SLC46A1 protein, human
  • Folic Acid

Associated data

  • RefSeq/NP_542400