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URL of this page: https://medlineplus.gov/genetics/gene/slc46a1/

SLC46A1 gene

solute carrier family 46 member 1

Normal Function

The SLC46A1 gene provides instructions for making a protein called the proton-coupled folate transporter (PCFT). PCFT is important for normal functioning of intestinal epithelial cells, which are cells that line the walls of the intestine. These cells have fingerlike projections called microvilli that absorb nutrients from food as it passes through the intestine. Based on their appearance, groups of these microvilli are known collectively as the brush border. PCFT is involved in the process of using energy to move certain B vitamins called folates across the brush border membrane for absorption, a mechanism called active transport. It is also involved in the transport of folates between the brain and the fluid that surrounds it (cerebrospinal fluid). Folates are important for many cell functions, including the production of DNA and its chemical cousin, RNA.

Health Conditions Related to Genetic Changes

Hereditary folate malabsorption

More than 10 mutations in the SLC46A1 gene have been identified in people with hereditary folate malabsorption. These mutations cause the substitution of one protein building block (amino acid) for another amino acid in the PCFT protein, or result in a PCFT protein that is shorter than normal. The mutated PCFT protein has little or no activity. In some cases the abnormal protein is not transported to the cell membrane, and so it is unable to perform its function. PCFT inactivity impairs the body's ability to absorb folates from food, leading to the signs and symptoms of hereditary folate malabsorption.

More About This Health Condition

Other Names for This Gene

  • HCP1
  • heme carrier protein 1
  • MGC9564
  • PCFT
  • proton-coupled folate transporter
  • solute carrier family 46 (folate transporter), member 1
  • solute carrier family 46, member 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Andrews NC. When is a heme transporter not a heme transporter? When it's a folate transporter. Cell Metab. 2007 Jan;5(1):5-6. doi: 10.1016/j.cmet.2006.12.004. Citation on PubMed
  • Goldman ID. Hereditary Folate Malabsorption. 2008 Jun 17 [updated 2024 Feb 15]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1673/ Citation on PubMed
  • Gonen N, Bram EE, Assaraf YG. PCFT/SLC46A1 promoter methylation and restoration of gene expression in human leukemia cells. Biochem Biophys Res Commun. 2008 Nov 28;376(4):787-92. doi: 10.1016/j.bbrc.2008.09.074. Epub 2008 Sep 24. Citation on PubMed
  • Ifergan I, Assaraf YG. Molecular mechanisms of adaptation to folate deficiency. Vitam Horm. 2008;79:99-143. doi: 10.1016/S0083-6729(08)00404-4. Citation on PubMed
  • Lasry I, Berman B, Straussberg R, Sofer Y, Bessler H, Sharkia M, Glaser F, Jansen G, Drori S, Assaraf YG. A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function. Blood. 2008 Sep 1;112(5):2055-61. doi: 10.1182/blood-2008-04-150276. Epub 2008 Jun 17. Citation on PubMed
  • Min SH, Oh SY, Karp GI, Poncz M, Zhao R, Goldman ID. The clinical course and genetic defect in the PCFT gene in a 27-year-old woman with hereditary folate malabsorption. J Pediatr. 2008 Sep;153(3):435-7. doi: 10.1016/j.jpeds.2008.04.009. Citation on PubMed or Free article on PubMed Central
  • Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H. Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. doi: 10.1124/jpet.107.122606. Epub 2007 May 2. Citation on PubMed
  • Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID. 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. Citation on PubMed
  • Unal ES, Zhao R, Qiu A, Goldman ID. N-linked glycosylation and its impact on the electrophoretic mobility and function of the human proton-coupled folate transporter (HsPCFT). Biochim Biophys Acta. 2008 Jun;1778(6):1407-14. doi: 10.1016/j.bbamem.2008.03.009. Epub 2008 Mar 20. Citation on PubMed or Free article on PubMed Central
  • Wolf G. Identification of proton-coupled high-affinity human intestinal folate transporter mutated in human hereditary familial folate malabsorption. Nutr Rev. 2007 Dec;65(12 Pt 1):554-7. doi: 10.1301/nr.2007.dec.554-557. Citation on PubMed
  • Zhao R, Goldman ID. The molecular identity and characterization of a Proton-coupled Folate Transporter--PCFT; biological ramifications and impact on the activity of pemetrexed. Cancer Metastasis Rev. 2007 Mar;26(1):129-39. doi: 10.1007/s10555-007-9047-1. Citation on PubMed
  • Zhao R, Matherly LH, Goldman ID. Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev Mol Med. 2009 Jan 28;11:e4. doi: 10.1017/S1462399409000969. Citation on PubMed or Free article on PubMed Central
  • Zhao R, Min SH, Qiu A, Sakaris A, Goldberg GL, Sandoval C, Malatack JJ, Rosenblatt DS, Goldman ID. The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. Blood. 2007 Aug 15;110(4):1147-52. doi: 10.1182/blood-2007-02-077099. Epub 2007 Apr 19. Citation on PubMed or Free article on PubMed Central
  • Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, Goldman ID. The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol Pharmacol. 2008 Sep;74(3):854-62. doi: 10.1124/mol.108.045443. Epub 2008 Jun 4. Citation on PubMed or Free article on PubMed Central

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.