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

Summary

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: mouse all
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Genomic context

Location:: 4q24

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (102251041..102345482, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (105565252..105659701, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (103172198..103266639, complement)

Chromosome 4 - NC_000004.12 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 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?

Does SLC39A8 Ala391Thr Confer Risk of Chronic Liver Disease?
Title: Does SLC39A8 Ala391Thr Confer Risk of Chronic Liver Disease?
Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.
Title: Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.
Identification of ZIP8-induced ferroptosis as a major type of cell death in monocytes under sepsis conditions.
Title: Identification of ZIP8-induced ferroptosis as a major type of cell death in monocytes under sepsis conditions.
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.
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.
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.
ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses.
Title: ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses.
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (50)

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: SLC39A8-CDG	not available

EBI GWAS Catalog

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH92985 (e-PCR)
- UniSTS:91697

RH65581 (e-PCR)
- UniSTS:12600

G34418 (e-PCR)
- UniSTS:3410

G20730 (e-PCR)
- UniSTS:56976

A006D35 (e-PCR)
- UniSTS:56977

D4S2644 (e-PCR)
- UniSTS:62652

RH78848 (e-PCR)
- UniSTS:49618

SHGC-36631 (e-PCR)
- UniSTS:26839

PMC321570P6 (e-PCR)
- UniSTS:273120

SHGC-50443 (e-PCR)
- UniSTS:5622

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables monoatomic cation:bicarbonate symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables monoatomic cation:bicarbonate symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
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
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 canonical NF-kappaB signal transduction	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	IBA Inferred from Biological aspect of Ancestor more info
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
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
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

NG_047177.1 RefSeqGene

Range

5017..88833

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

B4E2H3, Q96SM9, Q9BVC0, Q9C0K1, Q9NSA4

UniProtKB/TrEMBL

A0A804HKW0

Related

ENSP00000349174.4, ENST00000356736.5

Conserved Domains (1) summary

pfam02535
Location:126 → 451

Zip; ZIP Zinc transporter
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/TrEMBL

A0A804HKW0

Conserved Domains (1) summary

pfam02535
Location:126 → 422

Zip; ZIP Zinc transporter
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
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

B4E2H3, Q96SM9, Q9BVC0, Q9C0K1, Q9NSA4

UniProtKB/TrEMBL

A0A804HKW0

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

102251041..102345482 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A804HKW0

Conserved Domains (1) summary

pfam02535
Location:126 → 422

Zip; ZIP Zinc transporter
XM_047416070.1 → XP_047272026.1 metal cation symporter ZIP8 isoform X1

UniProtKB/Swiss-Prot

B4E2H3, Q96SM9, Q9BVC0, Q9C0K1, Q9NSA4
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
XM_047416071.1 → XP_047272027.1 metal cation symporter ZIP8 isoform X4
XM_024454183.2 → XP_024309951.1 metal cation symporter ZIP8 isoform X3

UniProtKB/TrEMBL

A0A804HJR0

Related

ENSP00000507611.1, ENST00000684386.1

Conserved Domains (1) summary

cl00437
Location:126 → 281

Zip; ZIP Zinc transporter

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

105565252..105659701 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054350709.1 → XP_054206684.1 metal cation symporter ZIP8 isoform X5
XM_054350705.1 → XP_054206680.1 metal cation symporter ZIP8 isoform X1

UniProtKB/Swiss-Prot

B4E2H3, Q96SM9, Q9BVC0, Q9C0K1, Q9NSA4
XM_054350706.1 → XP_054206681.1 metal cation symporter ZIP8 isoform X2
XM_054350708.1 → XP_054206683.1 metal cation symporter ZIP8 isoform X4
XM_054350707.1 → XP_054206682.1 metal cation symporter ZIP8 isoform X3