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
109.20191205	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?

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.
p.Arg178Gln represents a new category of loss-of-function mutations and that the study of "gating residues" is necessary in order to fully understand the action mechanism of FPN1.
Title: The <i>SLC40A1</i> R178Q mutation is a recurrent cause of hemochromatosis and is associated with a novel pathogenic mechanism.
These and other data suggest that iron handling and the HAMP-FPN axis regulation in FRDA cardiac cells are hampered and that FPN may have new, still not fully understood, functions. These findings underline the complexity of the cardiac iron homeostasis.
Title: New Insights into the Hepcidin-Ferroportin Axis and Iron Homeostasis in iPSC-Derived Cardiomyocytes from Friedreich's Ataxia Patient.
The mean corpuscular volume (MCV) values of gain-of-function FPN1 mutation patients were positively associated with serum transferrin saturations, whereas MCVs of loss-of-function FPN1 mutation patients were not, supporting that erythroblasts donate iron to blood through FPN1 in response to serum iron levels.
Title: Ferroportin deficiency in erythroid cells causes serum iron deficiency and promotes hemolysis due to oxidative stress.
Regarding the rs13015236 single nucleotide polymorphisms in SLC40A1, the presence of a C allele could protect against porphyria cutanea tarda patients of mixed ancestry.
Title: SLC40A1 and CP single nucleotide polymorphisms in porphyria cutanea tarda patients of mixed ancestry.
Ca(2+) is required for human Fpn transport activity
Title: Calcium is an essential cofactor for metal efflux by the ferroportin transporter family.
SLC40A1 expression is increased in the intestine of patients with type 2 diabetes in association with iron stores and serum hepcidin levels.
Title: Increased Small Intestine Expression of Non-Heme Iron Transporters in Morbidly Obese Patients With Newly Diagnosed Type 2 Diabetes.
In this study, we identified three domestic sporadic families of hereditary hemochromatosis in China and demonstrated mutations in HFE and SLC40A1 respectively.
Title: Identification of hereditary hemochromatosis pedigrees and a novel SLC40A1 mutation in Chinese population.
The 1st 3D model of human ferroportin was used to study disease-associated mutations to determine the role of conserved residues in protein stability and iron transport. Molecular mechanisms critical for ferroportin endocytosis include at least 3 fundamental steps: hepcidin binding, structural reorganization of the N- and C-ter ferroportin lobes, and ferroportin ubiquitination.
Title: Deciphering the molecular basis of ferroportin resistance to hepcidin: Structure/function analysis of rare SLC40A1 missense mutations found in suspected hemochromatosis type 4 patients.

Submit: New GeneRIF Correction See all GeneRIFs (121)

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

NHGRI GWAS Catalog

Description
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. NHGRI GWA Catalog NHGRI GWA 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
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: 304 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
ferrous iron 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
cell	IEA Inferred from Electronic Annotation 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 109.20191205

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)