SLC39A6 solute carrier family 39 member 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC39A6provided by HGNC
Official Full Name: solute carrier family 39 member 6provided by HGNC
Primary source: HGNC:HGNC:18607
See related: Ensembl:ENSG00000141424 MIM:608731; AllianceGenome:HGNC:18607
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LIV1; ZIP6; LIV-1
Summary: Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A6 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Mar 2008]
Expression: Broad expression in prostate (RPKM 62.4), endometrium (RPKM 31.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 18q12.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (36108531..36129340, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (36300097..36320904, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (33688494..33709303, complement)

Chromosome 18 - NC_000018.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure.
Title: Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure.
Suppression of SLC39A6-CREB1 axis in liver cancer causes PCK1-mediated mitochondrial dysfunction.
Title: Suppression of SLC39A6-CREB1 axis in liver cancer causes PCK1-mediated mitochondrial dysfunction.
Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse.
Title: Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse.
Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer.
Title: Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer.
The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis.
Title: The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis.
ZIP10 is predominantly expressed in the interfollicular epidermis, epidermal appendages and hair follicles. ZIP10 depletion resulted in epidermal malformations in a reconstituted human skin model via downregulation of the epigenetic enzyme histone acetyltransferase (HAT). Decreased HAT activity, resulting from either ZIP10 depletion or treatment with the zinc chelator TPEN, was readily restored by zinc supplementation.
Title: The epithelial zinc transporter ZIP10 epigenetically regulates human epidermal homeostasis by modulating histone acetyltransferase activity.
SLC39A6 is involved in gastric adenocarcinoma, and genotype at SLC39A6 rs1050631 can predict post-resection prognosis of gastric adenocarcinoma patients, at least in a population in an area with high gastric adenocarcinoma incidence.
Title: Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.
These data demonstrate that LIV-1-GRPEL1 axis dually regulates mitotic exit as well as apoptosis by interacting with PP2A B55alpha and AIF.
Title: The LIV-1-GRPEL1 axis adjusts cell fate during anti-mitotic agent-damaged mitosis.
this work shows that zinc entry into activated lymphocytes depends on Zip6 and that this transporter is essential for the correct function of the cellular activation machinery
Title: Zip6 Transporter Is an Essential Component of the Lymphocyte Activation Machinery.
ZIP6 deficiency disturbs intracellular Zn2+ homeostasis, leading to increased cell survival in hypoxia and reduced E-cadherin expression, indicating that decreased ZIP6 expression is strongly associated with resistance to hypoxia.
Title: Zinc and its transporter ZIP6 are key mediators of breast cancer cell survival under high glucose conditions.

Submit: New GeneRIF Correction See all GeneRIFs (36)

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

EBI GWAS Catalog

Description
Genome-wide association study identifies common variants in SLC39A6 associated with length of survival in esophageal squamous-cell carcinoma. 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)

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of SLC39A6	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
enables monoatomic cation:bicarbonate symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables zinc ion transmembrane transporter activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in bicarbonate transport	IEA Inferred from Electronic Annotation more info
involved_in epithelial to mesenchymal transition	IDA Inferred from Direct Assay more info	PubMed
involved_in epithelial to mesenchymal transition	IEA Inferred from Electronic Annotation more info
involved_in epithelial to mesenchymal transition	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 lymphocyte activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in metal ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info
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	IDA Inferred from Direct Assay 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	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	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	HDA more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in lamellipodium membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lamellipodium membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: zinc transporter ZIP6

Names: LIV-1 protein, estrogen regulated; ZIP-6; ZRT/IRT-like protein 6; estrogen-regulated protein LIV-1; solute carrier family 39 (metal ion transporter), member 6; solute carrier family 39 (zinc transporter), member 6; zinc transporter 6; zrt- and Irt-like protein 6

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.

mRNA and Protein(s)

NM_001099406.2 → NP_001092876.1 zinc transporter ZIP6 isoform 2

See identical proteins and their annotated locations for NP_001092876.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and 3' UTR, and lacks exons in the 5' and 3' coding regions (compared to variant 1), resulting in the use of a downstream translation initiation codon. The encoded protein (isoform 2) is shorter at both the N- and C-termini, compared to isoform 1.

Source sequence(s)

AC091060, BC039498, DC414741

Consensus CDS

CCDS45854.1

UniProtKB/TrEMBL

B4DWH6

Related

ENSP00000401139.1, ENST00000440549.6

Conserved Domains (1) summary

pfam02535
Location:48 → 431

Zip; ZIP Zinc transporter
NM_012319.4 → NP_036451.4 zinc transporter ZIP6 isoform 1 precursor

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC091060

Consensus CDS

CCDS42428.1

UniProtKB/Swiss-Prot

B4DR49, B4E224, Q13433, Q8IXR3, Q96HP5

Related

ENSP00000269187.4, ENST00000269187.10

Conserved Domains (1) summary

pfam02535
Location:323 → 742

Zip; ZIP Zinc transporter