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SLC39A8 solute carrier family 39 member 8 [ Homo sapiens (human) ]

Gene ID: 64116, updated on 29-Mar-2023

Summary

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Official Symbol
SLC39A8provided by HGNC
Official Full Name
solute carrier family 39 member 8provided by HGNC
Primary source
HGNC:HGNC:20862
See related
Ensembl:ENSG00000138821 MIM:608732; AllianceGenome:HGNC:20862
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
ZIP8; CDG2N; PP3105; BIGM103; LZT-Hs6
Summary
This gene encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import of zinc at the onset of inflammation. It is also thought to be the primary transporter of the toxic cation cadmium, which is found in cigarette smoke. Multiple transcript variants encoding different isoforms have been found for this gene. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Oct 2008]
Expression
Biased expression in lung (RPKM 46.9), colon (RPKM 11.2) and 13 other tissues See more
Orthologs
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Genomic context

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See SLC39A8 in Genome Data Viewer
Location:
4q24
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (102251041..102345482, complement)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (105565252..105659701, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (103172198..103266639, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:103131208-103131806 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:103131807-103132405 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:103188587-103189786 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:103242691-103243218 Neighboring gene RNA, 7SL, cytoplasmic 728, pseudogene Neighboring gene uncharacterized LOC105377621 Neighboring gene zinc finger protein 705A pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Deficiency in the zinc transporter ZIP8 impairs epithelia renewal and enhances lung fibrosis. Foster PS, et al. J Clin Invest, 2022 Jun 1. PMID 35642632, Free PMC Article
  2. Effects of individual amino acid mutations of zinc transporter ZIP8 on manganese- and cadmium-transporting activity. Fujishiro H, et al. Biochem Biophys Res Commun, 2022 Aug 6. PMID 35636252
  3. The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization. Liang ZL, et al. Int J Mol Sci, 2021 Oct 22. PMID 34768831, Free PMC Article
  4. C Deletion at the re74650330 Locus of the SLC39A8 Gene (rs74650330) Increases the Risk of Coronary Artery Disease in Individuals with Low-Density Lipoprotein Cholesterol Levels. Zhang J, et al. Genet Test Mol Biomarkers, 2021 Oct. PMID 34672770
  5. N-glycome analysis detects dysglycosylation missed by conventional methods in SLC39A8 deficiency. Park JH, et al. J Inherit Metab Dis, 2020 Nov. PMID 32852845, Free PMC Article

See all (71) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Calcium and the Ca-ATPase SPCA1 modulate plasma membrane abundance of ZIP8 and ZIP14 to regulate Mn(II) uptake in brain microvascular endothelial cells.
    Title: Calcium and the Ca-ATPase SPCA1 modulate plasma membrane abundance of ZIP8 and ZIP14 to regulate Mn(II) uptake in brain microvascular endothelial cells.
  2. Effects of individual amino acid mutations of zinc transporter ZIP8 on manganese- and cadmium-transporting activity.
    Title: Effects of individual amino acid mutations of zinc transporter ZIP8 on manganese- and cadmium-transporting activity.
  3. Deficiency in the zinc transporter ZIP8 impairs epithelia renewal and enhances lung fibrosis.
    Title: Deficiency in the zinc transporter ZIP8 impairs epithelia renewal and enhances lung fibrosis.
  4. ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses.
    Title: ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses.
  5. C Deletion at the re74650330 Locus of the SLC39A8 Gene (rs74650330) Increases the Risk of Coronary Artery Disease in Individuals with Low-Density Lipoprotein Cholesterol Levels.
    Title: C Deletion at the re74650330 Locus of the SLC39A8 Gene (rs74650330) Increases the Risk of Coronary Artery Disease in Individuals with Low-Density Lipoprotein Cholesterol Levels.
  6. Manganese transport in mammals by zinc transporter family proteins, ZNT and ZIP.
    Title: Manganese transport in mammals by zinc transporter family proteins, ZNT and ZIP.
  7. The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.
    Title: The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.
  8. Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.
    Title: Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.
  9. N-glycome analysis detects dysglycosylation missed by conventional methods in SLC39A8 deficiency.
    Title: N-glycome analysis detects dysglycosylation missed by conventional methods in SLC39A8 deficiency.
  10. HIF-1alpha Dependent Upregulation of ZIP8, ZIP14, and TRPA1 Modify Intracellular Zn(2+) Accumulation in Inflammatory Synoviocytes.
    Title: HIF-1α Dependent Upregulation of ZIP8, ZIP14, and TRPA1 Modify Intracellular Zn(2+) Accumulation in Inflammatory Synoviocytes.
Submit: New GeneRIF Correction See all GeneRIFs (47)

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
SLC39A8-CDG
MedGen: C4225234 OMIM: 616721 GeneReviews: Not available
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EBI GWAS Catalog

Description
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.
EBI GWAS Catalog
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog
Biological, clinical and population relevance of 95 loci for blood lipids.
EBI GWAS Catalog
Discovery and refinement of loci associated with lipid levels.
EBI GWAS Catalog
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
EBI GWAS Catalog
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables monoatomic cation:bicarbonate symporter activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables monoatomic cation:bicarbonate symporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables zinc ion transmembrane transporter activity TAS
Traceable Author Statement
more info
  
enables zinc:bicarbonate symporter activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of arginine metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in bicarbonate transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cadmium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of cartilage homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular detoxification of cadmium ion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cobalt ion transport ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of extracellular matrix organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in intracellular manganese ion homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in intracellular monoatomic cation homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in intracellular zinc ion homeostasis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in iron ion import across plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of leukocyte adhesion to arterial endothelial cell ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in manganese ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in mercury ion transport IEA
Inferred from Electronic Annotation
more info
  
involved_in mitochondrial manganese ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_negative_effect negative regulation of I-kappaB kinase/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_negative_effect negative regulation of inflammatory response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in plasma membrane selenite transport IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of protein N-linked glycosylation ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of regulation of DNA-templated transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of membrane potential IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in zinc ion import across plasma membrane IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in zinc ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in zinc ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in zinc ion transmembrane transport TAS
Traceable Author Statement
more info
  
involved_in zinc ion transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in apical 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 lysosomal membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in organelle 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
metal cation symporter ZIP8
Names
BCG induced integral membrane protein BIGM103
BCG-induced integral membrane protein in monocyte clone 103 protein
LIV-1 subfamily of ZIP zinc transporter 6
ZIP-8
ZRT/IRT-like protein 8
Zinc transporter 8
Zrt- and Irt-like protein 8
solute carrier family 39 (metal ion transporter), member 8
zinc transporter ZIP8

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

  1. NG_047177.1 RefSeqGene

    Range
    5017..88833
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001135146.2 → NP_001128618.1  metal cation symporter ZIP8 isoform a precursor

    See identical proteins and their annotated locations for NP_001128618.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (a).
    Source sequence(s)
    AP002023, BC001320, BC012125, DR006301
    Consensus CDS
    CCDS3656.1
    UniProtKB/Swiss-Prot
    Q9C0K1, Q9NSA4
    UniProtKB/TrEMBL
    A0A024RDG0
    Related
    ENSP00000349174.4, ENST00000356736.5
    Conserved Domains (1) summary
    pfam02535
    Location:126 → 451
    Zip; ZIP Zinc transporter

  2. NM_001135147.1 → NP_001128619.1  metal cation symporter ZIP8 isoform b precursor

    See identical proteins and their annotated locations for NP_001128619.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and contains additional coding exons in the 3' CDS, compared to variant 1. The resulting protein (isoform b) has a shorter and distinct C-terminus, compared to isoform a.
    Source sequence(s)
    AC098487, AK304274, AP002023, BF000600, CA438467
    UniProtKB/Swiss-Prot
    Q9C0K1
    Conserved Domains (1) summary
    pfam02535
    Location:126 → 422
    Zip; ZIP Zinc transporter

  3. NM_001135148.2 → NP_001128620.1  metal cation symporter ZIP8 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has a distinct 5' exon, compared to variant 1. The resulting protein (isoform c) has a shorter and distinct N-terminus, compared to isoform a.
    Source sequence(s)
    AK027652, AP002023, BC001320
    UniProtKB/Swiss-Prot
    Q9C0K1
    Related
    ENST00000683401.1
    Conserved Domains (1) summary
    pfam02535
    Location:59 → 384
    Zip; ZIP Zinc transporter

  4. NM_022154.5 → NP_071437.3  metal cation symporter ZIP8 isoform a precursor

    See identical proteins and their annotated locations for NP_071437.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AP002023, BC001320, BC012125, BI823248
    Consensus CDS
    CCDS3656.1
    UniProtKB/Swiss-Prot
    Q9C0K1, Q9NSA4
    UniProtKB/TrEMBL
    A0A024RDG0
    Related
    ENSP00000378310.2, ENST00000394833.6
    Conserved Domains (1) summary
    pfam02535
    Location:126 → 451
    Zip; ZIP Zinc transporter

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    102251041..102345482 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024454184.2 → XP_024309952.1  metal cation symporter ZIP8 isoform X5

    Conserved Domains (1) summary
    pfam02535
    Location:126 → 422
    Zip; ZIP Zinc transporter

  2. XM_047416070.1 → XP_047272026.1  metal cation symporter ZIP8 isoform X1

    UniProtKB/Swiss-Prot
    Q9NSA4
    UniProtKB/TrEMBL
    A0A024RDG0

  3. XM_017008541.2 → XP_016864030.1  metal cation symporter ZIP8 isoform X2

    UniProtKB/Swiss-Prot
    Q9C0K1
    Conserved Domains (1) summary
    pfam02535
    Location:59 → 384
    Zip; ZIP Zinc transporter

  4. XM_047416071.1 → XP_047272027.1  metal cation symporter ZIP8 isoform X4

  5. XM_024454183.2 → XP_024309951.1  metal cation symporter ZIP8 isoform X3

    Related
    ENSP00000507611.1, ENST00000684386.1
    Conserved Domains (1) summary
    cl00437
    Location:126 → 281
    Zip; ZIP Zinc transporter

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    105565252..105659701 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054350709.1 → XP_054206684.1  metal cation symporter ZIP8 isoform X5

  2. XM_054350705.1 → XP_054206680.1  metal cation symporter ZIP8 isoform X1

  3. XM_054350706.1 → XP_054206681.1  metal cation symporter ZIP8 isoform X2

  4. XM_054350708.1 → XP_054206683.1  metal cation symporter ZIP8 isoform X4

  5. XM_054350707.1 → XP_054206682.1  metal cation symporter ZIP8 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9C0K1.1 GenPept UniProtKB/Swiss-Prot:Q9C0K1

Gene LinkOut

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