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

    Gene ID: 6547, updated on 2-Nov-2024

    Summary

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    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

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    See SLC8A3 in Genome Data Viewer
    Location:
    14q24.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (70044215..70189405, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (64251720..64396975, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (70510932..70655668, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene ribosomal protein L7a pseudogene 6 Neighboring gene SPARC related modular calcium binding 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:70419797-70420298 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:70445787-70446286 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr14:70454077-70454578 Neighboring gene small nucleolar RNA, C/D box 169 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8650 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr14:70477330-70478529 Neighboring gene Sharpr-MPRA regulatory region 14883 Neighboring gene Sharpr-MPRA regulatory region 1041 Neighboring gene MPRA-validated peak2186 silencer Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr14:70527273-70528472 Neighboring gene Sharpr-MPRA regulatory region 1623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5884 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5885 Neighboring gene ADAM metallopeptidase domain 20 pseudogene Neighboring gene uncharacterized LOC107984686 Neighboring gene MPRA-validated peak2187 silencer Neighboring gene histone deacetylase complex subunit SAP25-like

    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 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?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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
    Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
    EBI GWAS Catalog
    Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
    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)

    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 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 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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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    NEW Try the new Transcript table

    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_047080.1 RefSeqGene

      Range
      39662..184398
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. 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

    1. 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_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      70044215..70189405 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047431711.1 → XP_047287667.1  sodium/calcium exchanger 3 isoform X4

    2. 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

    3. 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

    4. 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

    5. 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

    6. 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

    7. 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

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      64251720..64396975 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376628.1 → XP_054232603.1  sodium/calcium exchanger 3 isoform X3

    2. XM_054376629.1 → XP_054232604.1  sodium/calcium exchanger 3 isoform X4

    3. XM_054376627.1 → XP_054232602.1  sodium/calcium exchanger 3 isoform X2

    4. XM_054376626.1 → XP_054232601.1  sodium/calcium exchanger 3 isoform X1

      UniProtKB/Swiss-Prot
      P57103, Q5K3P6, Q5K3P7, Q8IUE9, Q8IUF0, Q8NFI7, Q96QG1, Q96QG2

    5. XM_054376630.1 → XP_054232605.1  sodium/calcium exchanger 3 isoform X4

    6. XM_054376632.1 → XP_054232607.1  sodium/calcium exchanger 3 isoform X7

    7. XM_054376631.1 → XP_054232606.1  sodium/calcium exchanger 3 isoform X6

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_182933.1: Suppressed sequence

      Description
      NM_182933.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P57103.2 GenPept UniProtKB/Swiss-Prot:P57103

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