SLC8A3 solute carrier family 8 member A3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC8A3provided by HGNC
Official Full Name: solute carrier family 8 member A3provided by HGNC
Primary source: HGNC:HGNC:11070
See related: Ensembl:ENSG00000100678 MIM:607991; AllianceGenome:HGNC:11070
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: NCX3
Summary: This gene encodes a member of the sodium/calcium exchanger integral membrane protein family. Na+/Ca2+ exchange proteins are involved in maintaining Ca2+ homeostasis in a wide variety of cell types. The protein is regulated by intracellular calcium ions and is found in both the plasma membrane and intracellular organellar membranes, where exchange of Na+ for Ca2+ occurs in an electrogenic manner. Alternative splicing has been observed for this gene and multiple variants have been described. [provided by RefSeq, Aug 2013]
Expression: Biased expression in brain (RPKM 2.0), adrenal (RPKM 0.3) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q24.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (70044215..70189405, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (64251720..64396975, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (70510932..70655668, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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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?

Sodium-calcium exchanger-3 regulates pain ""wind-up"": From human psychophysics to spinal mechanisms.
Title: Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.
The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer.
Title: The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer.
These results...suggest that cells can use a dynamic Ca(2+) signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle
Title: Glycosylation controls sodium-calcium exchanger 3 sub-cellular localization during cell cycle.
Structure-Dynamic Coupling Through Ca(2+)-Binding Regulatory Domains of Mammalian NCX Isoform/Splice Variants
Title: Structure-Dynamic Coupling Through Ca(2+)-Binding Regulatory Domains of Mammalian NCX Isoform/Splice Variants.
stimulation of NCX3 by PKA occurred through residue S524. This effect may well participate in the fight-or-flight response in skeletal muscle and the long-term potentiation in hippocampus.
Title: Differential regulation of the Na(+)-Ca(2+) exchanger 3 (NCX3) by protein kinase PKC and PKA.
In the discovery phase, 60 loci not previously associated with rheumatoid arthritis risk showed evidence for association and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level. When combining the discovery and validation cohorts, an intronic SNP in SLC8A3 was found to be associated with ACPA-positive rheumatoid arthritis at a genome-wide level of significance.
Title: A genome-wide association study identifies SLC8A3 as a susceptibility locus for ACPA-positive rheumatoid arthritis.
Ayloid beta mediates calpain cleavage of NCX3 in Alzheimer's disease brain.
Title: Calpain cleavage and inactivation of the sodium calcium exchanger-3 occur downstream of Aβ in Alzheimer's disease.
human macrophages and monocytes express NCX1 and NCX3 that operate in a bidirectional manner to restore [Ca(2+)](i) to generate Ca(2+) signals and to induce TNF-alpha production.
Title: Human macrophages and monocytes express functional Na(+)/Ca (2+) exchangers 1 and 3.
Functional studies, as well as mRNA and protein expression analyses, revealed that NCX1 and NCX3, but not NCX2, were divergently modulated during OPC differentiation into oligodendrocyte.
Title: New roles of NCX in glial cells: activation of microglia in ischemia and differentiation of oligodendrocytes.
the large cytosolic loop of NCX1, NCX2, and NCX3 is involved in acquisition of immunosuppressive drug specificity
Title: Immunosuppressive drugs, immunophilins, and functional expression of NCX isoforms.

Submit: New GeneRIF Correction See all GeneRIFs (22)

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
Genetic variants near PDGFRA are associated with corneal curvature in Australians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 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

G59549 (e-PCR)
- UniSTS:136711

G60387 (e-PCR)
- UniSTS:137493

SHGC-145504 (e-PCR)
- UniSTS:174615

WI-14913 (e-PCR)
- UniSTS:38176

REN46433 (e-PCR)
- UniSTS:371233

RH122533 (e-PCR)
- UniSTS:138535

SHGC-145531 (e-PCR)
- UniSTS:174632

SHGC-145542 (e-PCR)
- UniSTS:174640

RH44806 (e-PCR)
- UniSTS:5965

D14S681E (e-PCR)
- UniSTS:32923

D14S258 (e-PCR), detects polymorphism
- UniSTS:64714

SLC8A3 (e-PCR)
- UniSTS:506059

D14S1116 (e-PCR)
- UniSTS:9934

SHGC-145406 (e-PCR)
- UniSTS:174557

RH78238 (e-PCR)
- UniSTS:38888

SHGC-145433 (e-PCR)
- UniSTS:174574

D14S603 (e-PCR), detects polymorphism
- UniSTS:47346

SHGC-145103 (e-PCR)
- UniSTS:172531

D14S776 (e-PCR)
- UniSTS:53236

G65592 (e-PCR)
- UniSTS:225526

D14S258 (e-PCR), detects polymorphism
- UniSTS:78583

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium:sodium antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium:sodium antiporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables calcium:sodium antiporter activity	TAS Traceable Author Statement more info
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables monoatomic ion antiporter activity involved in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in calcium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell communication	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hypoxia	ISS Inferred from Sequence or Structural Similarity more info
involved_in hematopoietic progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within intracellular calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in learning	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within learning or memory	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in mitochondrial calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in mitochondrial calcium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within modulation of excitatory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in myelination	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in oligodendrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cardiac conduction	TAS Traceable Author Statement more info
involved_in regulation of skeletal muscle contraction	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within synapse organization	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in axon terminus	ISS Inferred from Sequence or Structural Similarity more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial outer membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in neuromuscular junction	ISS Inferred from Sequence or Structural Similarity more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in postsynapse	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
is_active_in sarcolemma	IBA Inferred from Biological aspect of Ancestor more info
located_in sarcolemma	ISS Inferred from Sequence or Structural Similarity more info
located_in sarcoplasm	IEA Inferred from Electronic Annotation more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: sodium/calcium exchanger 3

Names: Na(+)/Ca(2+)-exchange protein 3; sodium/calcium exchanger SLC8A3; solute carrier family 8 (sodium/calcium exchanger), member 3

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_047080.1 RefSeqGene

Range

39662..184398

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001130417.3 → NP_001123889.1 sodium/calcium exchanger 3 isoform G

See identical proteins and their annotated locations for NP_001123889.1

Status: REVIEWED

Description

Transcript Variant: This variant (g, also known as NCX3-tN.2) differs in the presence and absence of exons at its 5' end, compared to variant c. These differences result in a distinct 5' UTR and translation initiation at a downstream start codon, and an isoform (G) that is shorter than isoform C.

Source sequence(s)

AF510501, AL135747, BC142969, BX098112, DA351808

Consensus CDS

CCDS45131.1

UniProtKB/TrEMBL

B3KV80

Related

ENSP00000216568.7, ENST00000216568.11

Conserved Domains (1) summary

cl02522
Location:10 → 298

Calx-beta; Calx-beta domain
NM_033262.5 → NP_150287.1 sodium/calcium exchanger 3 isoform A precursor

See identical proteins and their annotated locations for NP_150287.1

Status: REVIEWED

Description

Transcript Variant: This variant (a) includes an alternate in-frame exon, lacks another alternate in-frame exon and uses an alternate in-frame splice site in the mid coding region, compared to variant c. The encoded isoform (A) is shorter than isoform C.

Source sequence(s)

AF510501, AJ304852, AL135747, BX098112

Consensus CDS

CCDS9799.1

UniProtKB/TrEMBL

A7E240

Related

ENSP00000433531.1, ENST00000528359.6

Conserved Domains (1) summary

TIGR00845
Location:1 → 925

caca; sodium/calcium exchanger 1
NM_058240.4 → NP_489479.1 sodium/calcium exchanger 3 isoform B precursor

See identical proteins and their annotated locations for NP_489479.1

Status: REVIEWED

Description

Transcript Variant: This variant (b) uses an alternate in-frame splice site in the mid coding region, compared to variant c. The encoded isoform (B) is shorter than isoform C.

Source sequence(s)

AF510502, AJ304853, AL135747, BX098112

Consensus CDS

CCDS53904.1

UniProtKB/TrEMBL

A7E240

Related

ENSP00000436688.1, ENST00000534137.5

Conserved Domains (1) summary

TIGR00845
Location:1 → 924

caca; sodium/calcium exchanger 1
NM_182932.3 → NP_891977.1 sodium/calcium exchanger 3 isoform D precursor

See identical proteins and their annotated locations for NP_891977.1

Status: REVIEWED

Description

Transcript Variant: This variant (d, also known as NCX3.2), lacks an alternate in-frame exon in the mid coding region, compared to variant c. The encoded isoform (D) is shorter than isoform C.

Source sequence(s)

AF510501, AL135747, BX098112

Consensus CDS

CCDS9800.1

UniProtKB/TrEMBL

A7E240

Related

ENSP00000349392.3, ENST00000356921.7

Conserved Domains (1) summary

TIGR00845
Location:1 → 921

caca; sodium/calcium exchanger 1
NM_182936.3 → NP_891981.1 sodium/calcium exchanger 3 isoform F

See identical proteins and their annotated locations for NP_891981.1

Status: REVIEWED

Description

Transcript Variant: This variant (f, also known as NCX3-tN.1) differs in the presence and absence of exons at its 5' end, compared to variant c. These differences result in a distinct 5' UTR and translation initiation at a downstream start codon, and an isoform (F) that is shorter than isoform C.

Source sequence(s)

AF510501, AK096553, AL135747, BX098112, DA351808

Consensus CDS

CCDS41967.1

UniProtKB/TrEMBL

B3KU59

Related

ENSP00000377863.2, ENST00000394330.6

Conserved Domains (1) summary

TIGR00845
Location:1 → 284

caca; sodium/calcium exchanger 1
NM_183002.3 → NP_892114.1 sodium/calcium exchanger 3 isoform C precursor

See identical proteins and their annotated locations for NP_892114.1

Status: REVIEWED

Description

Transcript Variant: This variant (c, also known as NCX3.3), encodes the longest isoform (C).

Source sequence(s)

AF510502, AL135747, BX098112

Consensus CDS

CCDS35498.1

UniProtKB/Swiss-Prot

P57103, Q5K3P6, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2

UniProtKB/TrEMBL

A7E240

Related

ENSP00000370669.2, ENST00000381269.6

Conserved Domains (1) summary

TIGR00845
Location:1 → 927

caca; sodium/calcium exchanger 1

RNA

NR_104122.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (h) lacks two alternate internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant c, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF510503, AL135747, BX098112

Related

ENST00000494208.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

70044215..70189405 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047431711.1 → XP_047287667.1 sodium/calcium exchanger 3 isoform X4
XM_017021608.2 → XP_016877097.1 sodium/calcium exchanger 3 isoform X3

UniProtKB/TrEMBL

A7E240

Related

ENSP00000516120.1, ENST00000705391.1

Conserved Domains (1) summary

TIGR00845
Location:1 → 921

caca; sodium/calcium exchanger 1
XM_017021606.2 → XP_016877095.1 sodium/calcium exchanger 3 isoform X1

UniProtKB/Swiss-Prot

P57103, Q5K3P6, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2

UniProtKB/TrEMBL

A7E240

Conserved Domains (1) summary

TIGR00845
Location:1 → 927

caca; sodium/calcium exchanger 1
XM_017021609.2 → XP_016877098.1 sodium/calcium exchanger 3 isoform X4

UniProtKB/TrEMBL

A7E240

Conserved Domains (4) summary

TIGR00845
Location:1 → 920

caca; sodium/calcium exchanger 1

pfam01699
Location:746 → 911

Na_Ca_ex; Sodium/calcium exchanger protein

pfam03160
Location:395 → 485

Calx-beta; Calx-beta domain

pfam16494
Location:253 → 374

Na_Ca_ex_C; C-terminal extension of sodium/calcium exchanger domain
XM_017021607.2 → XP_016877096.1 sodium/calcium exchanger 3 isoform X2

UniProtKB/TrEMBL

A7E240

Conserved Domains (4) summary

TIGR00845
Location:1 → 926

caca; sodium/calcium exchanger 1

pfam01699
Location:752 → 917

Na_Ca_ex; Sodium/calcium exchanger protein

pfam03160
Location:395 → 485

Calx-beta; Calx-beta domain

pfam16494
Location:253 → 374

Na_Ca_ex_C; C-terminal extension of sodium/calcium exchanger domain
XM_006720240.4 → XP_006720303.1 sodium/calcium exchanger 3 isoform X7

See identical proteins and their annotated locations for XP_006720303.1

UniProtKB/TrEMBL

B3KV80

Conserved Domains (1) summary

pfam01699
Location:130 → 295

Na_Ca_ex; Sodium/calcium exchanger protein
XM_017021611.2 → XP_016877100.1 sodium/calcium exchanger 3 isoform X6

UniProtKB/TrEMBL

B3KV80

Conserved Domains (1) summary

TIGR00845
Location:4 → 311

caca; sodium/calcium exchanger 1
XM_017021610.2 → XP_016877099.1 sodium/calcium exchanger 3 isoform X5

Alternate T2T-CHM13v2.0

Genomic

NC_060938.1 Alternate T2T-CHM13v2.0

Range

64251720..64396975 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054376628.1 → XP_054232603.1 sodium/calcium exchanger 3 isoform X3
XM_054376629.1 → XP_054232604.1 sodium/calcium exchanger 3 isoform X4
XM_054376627.1 → XP_054232602.1 sodium/calcium exchanger 3 isoform X2
XM_054376626.1 → XP_054232601.1 sodium/calcium exchanger 3 isoform X1

UniProtKB/Swiss-Prot

P57103, Q5K3P6, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2
XM_054376630.1 → XP_054232605.1 sodium/calcium exchanger 3 isoform X4
XM_054376632.1 → XP_054232607.1 sodium/calcium exchanger 3 isoform X7
XM_054376631.1 → XP_054232606.1 sodium/calcium exchanger 3 isoform X6

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_182933.1: Suppressed sequence

Description

NM_182933.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.