SLC40A1 solute carrier family 40 member 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC40A1provided by HGNC
Official Full Name: solute carrier family 40 member 1provided by HGNC
Primary source: HGNC:HGNC:10909
See related: Ensembl:ENSG00000138449 MIM:604653
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: FPN1; HFE4; MTP1; IREG1; MST079; MSTP079; SLC11A3
Summary: The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]
Expression: Broad expression in spleen (RPKM 192.7), ovary (RPKM 171.6) and 22 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2q32.2

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (189560590..189580811, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (190425316..190448478, complement)

Chromosome 2 - NC_000002.12 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?

Ferroportin downregulation promotes cell proliferation by modulating the Nrf2-miR-17-5p axis in multiple myeloma.
Title: Ferroportin downregulation promotes cell proliferation by modulating the Nrf2-miR-17-5p axis in multiple myeloma.
Local hepcidin increased intracellular iron overload via the degradation of ferroportin in the kidney.
Title: Local hepcidin increased intracellular iron overload via the degradation of ferroportin in the kidney.
The SLC40A1 p.Y333H mutation is associated with gain of function of ferroportin, representing one of the major aetiological factors of haemochromatosis in China.
Title: A novel SLC40A1 p.Y333H mutation with gain of function of ferroportin: A recurrent cause of haemochromatosis in China.
Findings establish FPN as a key lever in regulating iron balance and proliferation in multiple prostate cancer cell types.
Title: Effects of Ferroportin-Mediated Iron Depletion in Cells Representative of Different Histological Subtypes of Prostate Cancer.
miR-20b is identified to regulate intestinal FPN expression in vitro and in vivo, which will provide a potential target for intestinal iron exportation.
Title: MiR-20b Down-Regulates Intestinal Ferroportin Expression In Vitro and In Vivo.
Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells
Title: Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma.
High SLC40A1 expression is associated with acute myeloid leukemia.
Title: Low ferroportin expression in AML is correlated with good risk cytogenetics, improved outcomes and increased sensitivity to chemotherapy.
Enhanced expression of apical membrane- and basolateral membrane-localized DMT1 and FPN1 in UC human colon.
Title: Increased DMT1 and FPN1 expression with enhanced iron absorption in ulcerative colitis human colon.
Reduced expression of FPN1 and CP was identified as a potential signature for poor prognosis of adrenocortical carcinoma.
Title: Reduced expression of ferroportin1 and ceruloplasmin predicts poor prognosis in adrenocortical carcinoma.
IL-6 was also found to increase hepcidin transcription and release from human pulmonary artery smooth muscle cells (hPASMCs) suggesting a potential autocrine response. Hepcidin or IL-6 mediated iron accumulation contributes to proliferation in hPASMCs; ferroportin mediated cellular iron excretion limits proliferation.
Title: The Hepcidin/Ferroportin axis modulates proliferation of pulmonary artery smooth muscle cells.

Submit: New GeneRIF Correction See all GeneRIFs (129)

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
Hemochromatosis type 4 MedGen: C1853733 OMIM: 606069 GeneReviews: Not available	Compare labs
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. GeneReviews: Not available

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
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of SLC40A1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G32943 (e-PCR)
- UniSTS:117521

D2S2575 (e-PCR)
- UniSTS:36426

A009X19 (e-PCR)
- UniSTS:29515

PMC209405P1 (e-PCR)
- UniSTS:271991

RH16273 (e-PCR)
- UniSTS:47995

RH36364 (e-PCR)
- UniSTS:38527

STS-AA011593 (e-PCR)
- UniSTS:148

A002Q39 (e-PCR)
- UniSTS:17564

SGC34910 (e-PCR)
- UniSTS:62118

WI-16551 (e-PCR)
- UniSTS:45818

Homology

Homologs of the SLC40A1 gene: The SLC40A1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 340 organisms have orthologs with human gene SLC40A1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ferrous iron transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
identical protein binding	IEA Inferred from Electronic Annotation more info
iron ion transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
iron ion transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
iron ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
peptide hormone binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptide hormone binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cellular iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
cellular iron ion homeostasis	TAS Traceable Author Statement more info
divalent inorganic cation transport	IEA Inferred from Electronic Annotation more info
endothelium development	IEA Inferred from Electronic Annotation more info
iron ion export across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
iron ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
iron ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
iron ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
lymphocyte homeostasis	IEA Inferred from Electronic Annotation more info
multicellular organismal iron ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
regulation of transcription from RNA polymerase II promoter in response to iron	IEA Inferred from Electronic Annotation more info
spleen trabecula formation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
cytoplasm	TAS Traceable Author Statement more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
integral component of membrane	TAS Traceable Author Statement more info	PubMed
integral component of plasma membrane	IC Inferred by Curator more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
synaptic vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: solute carrier family 40 member 1

Names: iron regulated gene 1; solute carrier family 11 (proton-coupled divalent metal ion transporters), member 3; solute carrier family 40 (iron-regulated 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_009027.1 RefSeqGene

Range

5001..25222

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_837

mRNA and Protein(s)

NM_014585.6 → NP_055400.1 solute carrier family 40 member 1

See identical proteins and their annotated locations for NP_055400.1

Status: REVIEWED

Source sequence(s)

BC037733, DA806565

Consensus CDS

CCDS2299.1

UniProtKB/Swiss-Prot

Q9NP59

Related

ENSP00000261024.2, ENST00000261024.6

Conserved Domains (1) summary

pfam06963
Location:22 → 531

FPN1; Ferroportin1 (FPN1)

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p13 Primary Assembly

Range

189560590..189580811 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005246505.2 → XP_005246562.1 solute carrier family 40 member 1 isoform X1

See identical proteins and their annotated locations for XP_005246562.1

Conserved Domains (1) summary

pfam06963
Location:1 → 491

FPN1; Ferroportin1 (FPN1)
XM_017003938.2 → XP_016859427.1 solute carrier family 40 member 1 isoform X1

Conserved Domains (1) summary

pfam06963
Location:1 → 491

FPN1; Ferroportin1 (FPN1)