SLC39A14 solute carrier family 39 member 14 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC39A14provided by HGNC
Official Full Name: solute carrier family 39 member 14provided by HGNC
Primary source: HGNC:HGNC:20858
See related: Ensembl:ENSG00000104635 MIM:608736
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: HCIN; NET34; ZIP14; cig19; HMNDYT2; LZT-Hs4
Summary: This gene encodes a member of the the SLC39A family of divalent metal transporters that mediates the cellular uptake of manganese, zinc, iron, and cadmium. The encoded protein contains eight transmembrane domains, a histidine-rich motif, and a metalloprotease motif, and is expressed on the plasma membrane and the endocytic vesicle membrane. It is an important transporter of nontransferrin-bound iron and a critical regulator of manganese homeostasis. Naturally occurring mutations in this gene are associated with neurodegeneration with brain iron accumulation and early-onset parkinsonism-dystonia with hypermanganesemia. [provided by RefSeq, May 2017]
Expression: Broad expression in liver (RPKM 83.2), duodenum (RPKM 51.4) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8p21.3

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
109.20210226	current	GRCh38.p13 (GCF_000001405.39)	8	NC_000008.11 (22367278..22434129)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (22224791..22291642)

Chromosome 8 - NC_000008.11 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?

The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis.
Title: The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis.
solute carriers ZIP8 and ZIP14 regulate manganese accumulation in brain microvascular endothelial cells and control brain manganese levels
Title: The solute carriers ZIP8 and ZIP14 regulate manganese accumulation in brain microvascular endothelial cells and control brain manganese levels.
Both ZIP8 and ZIP14 have roles in manganese metabolism of alveolar epithelial cells.
Title: Manganese Uptake by A549 Cells is Mediated by Both ZIP8 and ZIP14.
Increased free Zn(2+) correlates with induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn(2+) -transporters, Zip8, Zip14, and ZnT8, in heart failure.
Title: Increased free Zn<sup>2+</sup> correlates induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn<sup>2+</sup> -transporters in heart failure.
Study shows that individuals harboring loss-of-function mutations in SLC30A10 or SLC39A14 develop inherited forms of Mn-induced neurotoxicity.
Title: Familial manganese-induced neurotoxicity due to mutations in SLC30A10 or SLC39A14.
SLC39A14 mutation is associated with dystonia.
Title: Novel founder intronic variant in SLC39A14 in two families causing Manganism and potential treatment strategies.
Expression of zinc transporters ZIP4, ZIP14 and ZnT9 in hepatic carcinogenesis-An immunohistochemical study
Title: Expression of zinc transporters ZIP4, ZIP14 and ZnT9 in hepatic carcinogenesis-An immunohistochemical study.
Missense mutations solute carrier family 39 (zinc transporter), member 14 (SLC39A14) impair manganese uptake.
Title: Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.
These results suggest that the wild type p53 plays a role in regulating ZIP14, but not DMT1 in HepG2 cells.
Title: The Tumor Suppressor, P53, Decreases the Metal Transporter, ZIP14.
Zip14 activity is needed for adaptation to endoplasmic reticulum stress in liver.
Title: Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress.

Submit: New GeneRIF Correction See all GeneRIFs (27)

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
Hypermanganesemia with dystonia 2 MedGen: C4310765 OMIM: 617013 GeneReviews: SLC39A14 Deficiency	Compare labs
Hyperostosis cranialis interna MedGen: C1840404 OMIM: 144755 GeneReviews: Not available	Compare labs

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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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of solute carrier family 39, member 14 (SLC39A14) in primary human brain microvascular endothelial cells	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

A009B38 (e-PCR)
- UniSTS:72961

RH11601 (e-PCR)
- UniSTS:75266

D8S1931 (e-PCR)
- UniSTS:12572

D8S439 (e-PCR), detects polymorphism
- UniSTS:53279

D8S1587 (e-PCR)
- UniSTS:59973

RH25295 (e-PCR)
- UniSTS:91981

1684 (e-PCR)
- UniSTS:51289

SHGC-56581 (e-PCR)
- UniSTS:20836

D8S1419E (e-PCR)
- UniSTS:151207

SLC39A14_3803 (e-PCR)
- UniSTS:462544

RH16598 (e-PCR)
- UniSTS:58067

G32392 (e-PCR)
- UniSTS:116980

Homology

Homologs of the SLC39A14 gene: The SLC39A14 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, and frog.
Orthologs from Annotation Pipeline: 345 organisms have orthologs with human gene SLC39A14
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
anion:cation symporter activity	ISS Inferred from Sequence or Structural Similarity more info
cadmium ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
ferrous iron transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
iron ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
manganese ion transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
zinc ion transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
zinc ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
cadmium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
cellular response to glucose stimulus	ISS Inferred from Sequence or Structural Similarity more info
cellular response to insulin stimulus	ISS Inferred from Sequence or Structural Similarity more info
cellular zinc ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular zinc ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
chondrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
gluconeogenesis	ISS Inferred from Sequence or Structural Similarity more info
import across plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
inorganic anion transport	IEA Inferred from Electronic Annotation more info
insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
iron import into cell	IMP Inferred from Mutant Phenotype more info	PubMed
iron ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
manganese ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
manganese ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cyclic-nucleotide phosphodiesterase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
regulation of hormone levels	ISS Inferred from Sequence or Structural Similarity more info
zinc ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
zinc ion import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
zinc ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
zinc ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
early endosome membrane	IDA Inferred from Direct Assay more info	PubMed
integral component of membrane	IDA Inferred from Direct Assay more info	PubMed
integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
late endosome membrane	IDA Inferred from Direct Assay more info	PubMed
lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: metal cation symporter ZIP14

Names: LIV-1 subfamily of ZIP zinc transporter 4; Zinc transporter ZIP14; Zrt-, Irt-like protein 14; solute carrier family 39 (metal ion transporter), member 14; solute carrier family 39 (zinc transporter), member 14; zrt- and Irt-like protein 14

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_054890.1 RefSeqGene

Range

5030..60488

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001128431.4 → NP_001121903.1 metal cation symporter ZIP14 isoform a precursor

See identical proteins and their annotated locations for NP_001121903.1

Status: REVIEWED

Source sequence(s)

AA181885, AK172810, D31887, DC323208

Consensus CDS

CCDS47823.1

UniProtKB/Swiss-Prot

Q15043

Related

ENSP00000370635.1, ENST00000381237.6

Conserved Domains (1) summary

pfam02535
Location:151 → 483

Zip; ZIP Zinc transporter
NM_001135153.3 → NP_001128625.1 metal cation symporter ZIP14 isoform a precursor

See identical proteins and their annotated locations for NP_001128625.1

Status: REVIEWED

Source sequence(s)

AA181885, AC087854, AK295807, DC423882

Consensus CDS

CCDS47823.1

UniProtKB/Swiss-Prot

Q15043

Related

ENSP00000289952.5, ENST00000289952.9

Conserved Domains (1) summary

pfam02535
Location:151 → 483

Zip; ZIP Zinc transporter
NM_001135154.3 → NP_001128626.1 metal cation symporter ZIP14 isoform c precursor

See identical proteins and their annotated locations for NP_001128626.1

Status: REVIEWED

Source sequence(s)

BC015770, DC323208

Consensus CDS

CCDS47822.1

UniProtKB/TrEMBL

A0A0S2Z534

Related

ENSP00000240095.6, ENST00000240095.10

Conserved Domains (2) summary

pfam02535
Location:151 → 445

Zip; ZIP Zinc transporter

pfam13900
Location:450 → 480

GVQW; Putative domain of unknown function
NM_001351655.2 → NP_001338584.1 metal cation symporter ZIP14 isoform a precursor

Status: REVIEWED

Source sequence(s)

AA181885, AC087854, AC105910

Consensus CDS

CCDS47823.1

Conserved Domains (1) summary

pfam02535
Location:151 → 483

Zip; ZIP Zinc transporter
NM_001351656.2 → NP_001338585.1 metal cation symporter ZIP14 isoform a precursor

Status: REVIEWED

Source sequence(s)

AA181885, AC087854, AC105910

Consensus CDS

CCDS47823.1

Conserved Domains (1) summary

pfam02535
Location:151 → 483

Zip; ZIP Zinc transporter
NM_001351657.2 → NP_001338586.1 metal cation symporter ZIP14 isoform d

Status: REVIEWED

Source sequence(s)

AA181885, AC087854, AC105910

Conserved Domains (1) summary

pfam02535
Location:161 → 493

Zip; ZIP Zinc transporter
NM_001351658.2 → NP_001338587.1 metal cation symporter ZIP14 isoform d

Status: REVIEWED

Source sequence(s)

AA181885, AC087854, AC105910

Conserved Domains (1) summary

pfam02535
Location:161 → 493

Zip; ZIP Zinc transporter
NM_001351659.2 → NP_001338588.1 metal cation symporter ZIP14 isoform d

Status: REVIEWED

Source sequence(s)

AA181885, AC087854, AC105910, DC369996

Conserved Domains (1) summary

pfam02535
Location:161 → 493

Zip; ZIP Zinc transporter
NM_001351660.2 → NP_001338589.1 metal cation symporter ZIP14 isoform a precursor

Status: REVIEWED

Source sequence(s)

AA181885, AC087854, AC105910

Consensus CDS

CCDS47823.1

Conserved Domains (1) summary

pfam02535
Location:151 → 483

Zip; ZIP Zinc transporter
NM_015359.6 → NP_056174.2 metal cation symporter ZIP14 isoform b precursor

See identical proteins and their annotated locations for NP_056174.2

Status: REVIEWED

Source sequence(s)

AA181885, AK172810, D31887, DC323208

Consensus CDS

CCDS6030.1

UniProtKB/Swiss-Prot

Q15043

Related

ENSP00000352779.5, ENST00000359741.9

Conserved Domains (1) summary

pfam02535
Location:151 → 483

Zip; ZIP Zinc transporter