How is a mutation in the SLC46A1 gene confirmed?

Confirmation typically involves a DNA sequencing test, such as targeted next‑generation sequencing or Sanger sequencing, focused on the SLC46A1 coding regions. The test is usually performed on a blood sample or a buccal swab. A genetic counselor interprets the results and discusses inheritance patterns with the family.

Can high‑dose folic acid supplements overcome the absorption defect caused by PCFT mutations?

High‑dose folic acid (often 5‑10 mg/day) can sometimes raise serum folate levels enough to alleviate anemia and some neurological symptoms, but it may not fully restore brain folate transport. In many patients, a combination of high‑dose folic acid and folinic acid (a more readily absorbed form) is used to achieve better outcomes.

What are the most common symptoms that might indicate hereditary folate malabsorption in a child?

Children with hereditary folate malabsorption often present with growth retardation, anemia that does not respond to iron or vitamin B12 therapy, developmental delays, and neurological symptoms such as ataxia or seizures. Parents may notice poor weight gain, fatigue, or irritability that persists despite a balanced diet. If these signs appear, a clinician may consider testing for SLC46A1 mutations.

Are there any dietary strategies that can help improve folate status in patients with SLC46A1 mutations?

Because PCFT functions best at low pH, consuming folate‑rich foods in the form of natural folates (e.g., leafy greens, legumes, fortified cereals) and taking supplements with meals can help. Avoiding high‑dose vitamin B12 or iron supplements that compete for absorption may also be beneficial. Regular monitoring of serum and red‑blood‑cell folate levels guides dietary adjustments.

SLC46A1 gene

The SLC46A1 gene encodes the proton‑coupled folate transporter (PCFT), a membrane protein essential for folate absorption in the small intestine and folate transport into the brain.

Overview

The SLC46A1 gene provides instructions for making a protein called the proton‑coupled folate transporter (PCFT). This protein is found within the membrane of cells, where it helps transport certain B vitamins called folates into the cell. PCFT is primarily found in cells that line the walls of the small intestine. These cells have finger‑like 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 transporting folates from food across the brush border membrane so they can be used by the body. PCFT is also found in the brain, where it is involved in the transport of folates between the brain and the surrounding fluid (cerebrospinal fluid).

Health Conditions Related to Genetic Changes

Hereditary folate malabsorption

Variants (also called mutations) in the SLC46A1 gene have been identified in people with hereditary folate malabsorption. This disorder interferes with the body's ability to take in (absorb) folates from food. The SLC46A1 gene variants can change single protein building blocks (amino acids) in the PCFT protein, or they can cause the cell to produce a PCFT protein that is shorter than normal. The altered PCFT protein has little or no activity. In some cases, the altered protein is missing from the cell membranes where it is needed to perform its function. Without functional PCFT, cells in the small intestine cannot absorb folates from food and cells in the brain cannot transport folate to the cerebrospinal fluid. These folate deficiencies result in the digestive issues, neurological problems, and other signs and symptoms of hereditary folate malabsorption.

Other Names for This Gene

HCP1
heme carrier protein 1
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

Tests of SLC46A1

Scientific Articles on PubMed

PubMed

Catalog of Genes and Diseases from OMIM

SOLUTE CARRIER FAMILY 46 (FOLATE TRANSPORTER), MEMBER 1; SLC46A1

Gene and Variant Databases

NCBI Gene
ClinVar

References

Goldman ID. Hereditary Folate Malabsorption. 2008 Jun 17 [updated 2026 Mar 25]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1673/ 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
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
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, Aluri S, Goldman ID. The proton-coupled folate transporter (PCFT‑SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. Mol Aspects Med. 2017 Feb;53:57-72. doi: 10.1016/j.mam.2016.09.002. Epub 2016 Sep 21. 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

Genomic Location

The SLC46A1 gene is found on chromosome 17.

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