SLC46A1 solute carrier family 46 member 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC46A1provided by HGNC
Official Full Name: solute carrier family 46 member 1provided by HGNC
Primary source: HGNC:HGNC:30521
See related: Ensembl:ENSG00000076351 MIM:611672; AllianceGenome:HGNC:30521
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: G21; HCP1; PCFT; hPCFT; HsPCFT
Summary: This gene encodes a transmembrane proton-coupled folate transporter protein that facilitates the movement of folate and antifolate substrates across cell membranes, optimally in acidic pH environments. This protein is also expressed in the brain and choroid plexus where it transports folates into the central nervous system. This protein further functions as a heme transporter in duodenal enterocytes, and potentially in other tissues like liver and kidney. Its localization to the apical membrane or cytoplasm of intestinal cells is modulated by dietary iron levels. Mutations in this gene are associated with autosomal recessive hereditary folate malabsorption disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]
Expression: Ubiquitous expression in duodenum (RPKM 45.1), small intestine (RPKM 21.0) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q11.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (28394642..28406592, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (29336494..29348065, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (26721661..26733230, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Loss of SLC46A1 decreases tumor iron content in hepatocellular carcinoma.
Title: Loss of SLC46A1 decreases tumor iron content in hepatocellular carcinoma.
Folate transporter dynamics and therapy with classic and tumor-targeted antifolates.
Title: Folate transporter dynamics and therapy with classic and tumor-targeted antifolates.
SLC46A1 Haplotype with Predicted Functional Impact has Prognostic Value in Breast Carcinoma.
Title: SLC46A1 Haplotype with Predicted Functional Impact has Prognostic Value in Breast Carcinoma.
Structural basis of antifolate recognition and transport by PCFT.
Title: Structural basis of antifolate recognition and transport by PCFT.
A proton-coupled folate transporter mutation causing hereditary folate malabsorption locks the protein in an inward-open conformation.
Title: A proton-coupled folate transporter mutation causing hereditary folate malabsorption locks the protein in an inward-open conformation.
Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds.
Title: Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds.
Decreased placental folate transporter expression and activity in first and second trimester in obese mothers.
Title: Decreased placental folate transporter expression and activity in first and second trimester in obese mothers.
SLC46A1 contributes to hepatic iron metabolism by importing heme in hepatocytes.
Title: SLC46A1 contributes to hepatic iron metabolism by importing heme in hepatocytes.
we report the same deep intronic mutation of c.1166-285T>G shared by four unrelated Japanese patients with hereditary folate malabsorption
Title: A deep intronic mutation of c.1166-285 T > G in SLC46A1 is shared by four unrelated Japanese patients with hereditary folate malabsorption (HFM).
Regulation of differential proton-coupled folate transporter gene expression in human tumors: transactivation by KLF15 with NRF-1 and the role of Sp1.
Title: Regulation of differential proton-coupled folate transporter gene expression in human tumors: transactivation by KLF15 with NRF-1 and the role of Sp1.

Submit: New GeneRIF Correction See all GeneRIFs (69)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Congenital defect of folate absorption MedGen: C0342705 OMIM: 229050 GeneReviews: Hereditary Folate Malabsorption	not available

EBI GWAS Catalog

Description
Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of solute carrier family 46 (folate transporter), member 1 (SLC46A1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-30073 (e-PCR)
- UniSTS:81793

SHGC-57890 (e-PCR)
- UniSTS:74184

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables folic acid binding	IEA Inferred from Electronic Annotation more info
enables folic acid transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables folic acid transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables folic acid transmembrane transporter activity	TAS Traceable Author Statement more info
enables folic acid:proton symporter activity	IC Inferred by Curator more info	PubMed
enables folic acid:proton symporter activity	IDA Inferred from Direct Assay more info	PubMed
NOT enables heme transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables heme transmembrane transporter activity	TAS Traceable Author Statement more info
enables methotrexate transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables proton transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in folate import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in folate transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in folic acid metabolic process	TAS Traceable Author Statement more info
involved_in folic acid transport	IDA Inferred from Direct Assay more info	PubMed
involved_in folic acid transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme metabolic process	TAS Traceable Author Statement more info
involved_in heme transport	IEA Inferred from Electronic Annotation more info
involved_in intestinal folate absorption	IC Inferred by Curator more info	PubMed
involved_in intracellular iron ion homeostasis	TAS Traceable Author Statement more info
involved_in methotrexate transport	IEA Inferred from Electronic Annotation more info
involved_in proton transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in brush border membrane	IEA Inferred from Electronic Annotation more info
located_in cell surface	HDA more info	PubMed
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: proton-coupled folate transporter

Names: heme carrier protein 1; solute carrier family 46 (folate transporter), member 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013306.1 RefSeqGene

Range

4999..16567

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_183

mRNA and Protein(s)

NM_001242366.3 → NP_001229295.1 proton-coupled folate transporter isoform 2

See identical proteins and their annotated locations for NP_001229295.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as HCP-1B) lacks an in-frame coding exon compared to variant 1. This results in a shorter isoform (2) missing an internal protein segment (containing one of the transmembrane domains) compared to isoform 1. This isoform was shown to have a different subcellular localization compared to the longer isoform 1 (PMID:17947394).

Source sequence(s)

AK074161, BC010691, BC022100, BC065365, DA013269, DA188147, DA436636, DA527125

Consensus CDS

CCDS74019.1

UniProtKB/TrEMBL

B4DJ17

Related

ENSP00000483652.1, ENST00000618626.1

Conserved Domains (2) summary

cd06174
Location:73 → 230

MFS; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of ...

pfam07690
Location:94 → 291

MFS_1; Major Facilitator Superfamily
NM_080669.6 → NP_542400.2 proton-coupled folate transporter isoform 1

See identical proteins and their annotated locations for NP_542400.2

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as HCP-1A) encodes the longer protein (isoform 1).

Source sequence(s)

AK054669, AK074161, BC022100, BC065365, DA013269, DA188147, DA436636, DA527125, DB121588

Consensus CDS

CCDS74020.1

UniProtKB/Swiss-Prot

Q1HE20, Q86T92, Q8TEG3, Q96FL0, Q96NT5

Related

ENSP00000480703.1, ENST00000612814.5

Conserved Domains (2) summary

cd06174
Location:73 → 443

MFS; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of ...

pfam07690
Location:94 → 407

MFS_1; Major Facilitator Superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

28394642..28406592 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047435280.1 → XP_047291236.1 proton-coupled folate transporter isoform X4
XM_047435279.1 → XP_047291235.1 proton-coupled folate transporter isoform X3
XM_017024110.2 → XP_016879599.1 proton-coupled folate transporter isoform X2
XM_005277786.4 → XP_005277843.1 proton-coupled folate transporter isoform X1

UniProtKB/TrEMBL

B4DJ17

Conserved Domains (2) summary

cd06174
Location:73 → 230

MFS; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of ...

pfam07690
Location:94 → 291

MFS_1; Major Facilitator Superfamily