Details for: SLC8A2

Gene ID: 6543

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SLC8A2

Ensembl ID: ENSG00000118160

Description: solute carrier family 8 member A2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • retinal bipolar neuron CL0000748
    CSI 6.54
    rCSI 12.24%
    PRS 76.91
  • L6b glutamatergic cortical neuron CL4023038
    CSI 4.99
    rCSI 15.59%
    PRS 72.76
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 4.37
    rCSI 25.72%
    PRS 71.81
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 4.09
    rCSI 9.95%
    PRS 69.19
  • type B pancreatic cell CL0000169
    CSI 3.67
    rCSI 8.13%
    PRS 86.61
  • pancreatic A cell CL0000171
    CSI 3.36
    rCSI 3.52%
    PRS 89.22
  • interneuron CL0000099
    CSI 3.05
    rCSI 6.12%
    PRS 79.15
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.77
    rCSI 3.57%
    PRS 72.57
  • cerebellar granule cell CL0001031
    CSI 2.59
    rCSI 3.8%
    PRS 80.53
  • cerebral cortex neuron CL0010012
    CSI 2.56
    rCSI 10.43%
    PRS 78.84
  • rod bipolar cell CL0000751
    CSI 2.47
    rCSI 4.45%
    PRS 81.03
  • pancreatic D cell CL0000173
    CSI 2.39
    rCSI 2.35%
    PRS 88.49
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2
    rCSI 4.78%
    PRS 74.94
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.92
    rCSI 2.39%
    PRS 69.25
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.8
    rCSI 2.15%
    PRS 71.52
  • central nervous system neuron CL2000029
    CSI 1.79
    rCSI 13.16%
    PRS 76.23
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.47
    rCSI 5.55%
    PRS 71.69
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.36
    rCSI 2.41%
    PRS 70.88
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.34
    rCSI 2.16%
    PRS 72.67
  • dopaminergic neuron CL0000700
    CSI 1.31
    rCSI 7.43%
    PRS 74.4
  • GABAergic neuron CL0000617
    CSI 1.31
    rCSI 4.39%
    PRS 71.81
  • medium spiny neuron CL1001474
    CSI 1.2
    rCSI 10.34%
    PRS 76.79
  • glutamatergic neuron CL0000679
    CSI 1.19
    rCSI 2.44%
    PRS 74.12
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.18
    rCSI 3.88%
    PRS 73.77
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.15
    rCSI 1.93%
    PRS 71.39
  • cerebellar neuron CL1001611
    CSI 1.06
    rCSI 9.29%
    PRS 74.61
  • serotonergic neuron CL0000850
    CSI 0.97
    rCSI 4.34%
    PRS 71.44
  • amacrine cell CL0000561
    CSI 0.95
    rCSI 2.75%
    PRS 77.34
  • direct pathway medium spiny neuron CL4023026
    CSI 0.77
    rCSI 18.55%
    PRS 69.02
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.57
    rCSI 2.04%
    PRS 69.37
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.39
    rCSI 9.36%
    PRS 69.44

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SLC8A2](/details-gene/6543) encodes the Solute Carrier Family 8 Member A2 protein, a sodium/calcium exchanger (NCX2) that plays a critical role in maintaining intracellular calcium homeostasis. As an antiporter, it facilitates the electrogenic exchange of sodium and calcium ions across the plasma membrane. The expression profile of [SLC8A2](/details-gene/6543) is predominantly concentrated in excitable cells, with exceptionally high significance observed in various neuronal subtypes of the central nervous system, including [retinal bipolar neuron](/details-cell/CL0000748) and glutamatergic cortical neurons. It is also a key marker in pancreatic islet cells, such as [type B pancreatic cell](/details-cell/CL0000169), suggesting its involvement in both neurotransmission and hormone secretion. Functionally, [SLC8A2](/details-gene/6543) is integral to processes such as synaptic plasticity, learning, memory, and the regulation of cytosolic calcium concentrations, as detailed in a review of the SLC8 gene family [Link](https://doi.org/10.1016/j.mam.2012.07.003). ## Cellular Roles and Expression Landscape The **Overall** expression data identifies [SLC8A2](/details-gene/6543) as a highly specialized gene whose function is central to the identity of specific neuronal and endocrine cell populations. Its most significant expression is in the [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 6.54), highlighting a crucial role in visual signal processing. The gene demonstrates profound importance within the cerebral cortex, where it is a defining marker for multiple classes of glutamatergic projection neurons, including [L6b glutamatergic cortical neuron](/details-cell/CL4023038) (CSI: 4.99) and [corticothalamic-projecting glutamatergic cortical neuron](/details-cell/CL4023013) (CSI: 4.37). Its significance extends to various GABAergic inhibitory neurons, such as the [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 2.77), indicating a broad role in regulating the excitation-inhibition balance within cortical microcircuits. The initial identification of [SLC8A2](/details-gene/6543) cDNA clones from brain tissue further supports its primary neurological function [Link](https://doi.org/10.1093/dnares/6.3.197). Beyond the central nervous system, [SLC8A2](/details-gene/6543) shows a distinct and significant expression signature in the endocrine pancreas. It is highly expressed in [type B pancreatic cell](/details-cell/CL0000169) (CSI: 3.67), [pancreatic A cell](/details-cell/CL0000171) (CSI: 3.36), and [pancreatic D cell](/details-cell/CL0000173) (CSI: 2.39). This pattern suggests a vital function in regulating the calcium-dependent exocytosis of hormones like insulin, glucagon, and somatostatin. ## Pathways and Molecular Function The primary molecular function of [SLC8A2](/details-gene/6543) is its activity as a [Calcium:sodium antiporter activity](/details-go/GO:0005432), which directly contributes to the [Reduction of cytosolic ca++ levels](/details-pathway/R-HSA-418359). This core mechanism underpins its involvement in a wide array of biological processes. Functionally, [SLC8A2](/details-gene/6543) is integral to neuronal signaling and cognitive functions. Gene Ontology annotations link it to [Long-term synaptic potentiation](/details-go/GO:0060291), [Learning or memory](/details-go/GO:0007611), and the [Modulation of excitatory postsynaptic potential](/details-go/GO:0098815). These processes are highly dependent on the precise regulation of calcium levels at the synapse. Consistent with this, its protein product is localized to critical synaptic compartments, including the [Postsynapse](/details-go/GO:0098794), [Presynapse](/details-go/GO:0098793), [Dendrite](/details-go/GO:0030425), and [Axon terminus](/details-go/GO:0043679). Reactome pathway analysis places [SLC8A2](/details-gene/6543) centrally within the [Sodium/calcium exchangers](/details-pathway/R-HSA-425561) pathway, which is part of the larger [Slc-mediated transmembrane transport](/details-pathway/R-HSA-425407) system. Its annotated involvement in [Cardiac conduction](/details-pathway/R-HSA-5576891) and [Muscle contraction](/details-pathway/R-HSA-397014) highlights the conserved role of NCX proteins in managing calcium fluxes in various types of excitable cells, although the provided expression data emphasizes its primary importance in the nervous and endocrine systems. ## Research Directions The specific expression pattern of [SLC8A2](/details-gene/6543) in distinct populations of excitable cells, combined with its fundamental role in calcium homeostasis, suggests it may be a critical node in both physiological function and disease. **Proposed Hypotheses:** 1. Given its high significance in glutamatergic and GABAergic neurons and its established role in synaptic plasticity, dysregulation of [SLC8A2](/details-gene/6543) activity in cortical neurons may impair the excitation-inhibition balance, contributing to the pathophysiology of seizure disorders or neurodevelopmental conditions such as autism, a field where other ion channel mutations have been implicated [Link](https://doi.org/10.1093/hmg/ddu056). 2. The prominent expression of [SLC8A2](/details-gene/6543) in pancreatic islet cells suggests that genetic variants affecting its transport efficiency could alter the dynamics of glucose-stimulated insulin secretion from [type B pancreatic cell](/details-cell/CL0000169), potentially representing a risk factor for the development or progression of type 2 diabetes. **Experimental Approach:** To test the hypothesis regarding its role in pancreatic function, a targeted experiment could be designed. A CRISPR-Cas9-mediated knockout of [SLC8A2](/details-gene/6543) could be generated in a human beta-cell line (e.g., EndoC-βH1). The impact of its deletion on cellular function would be assessed by comparing intracellular calcium dynamics in wild-type versus knockout cells using a fluorescent calcium indicator during a glucose challenge. Subsequent glucose-stimulated insulin secretion (GSIS) assays, with insulin levels quantified by ELISA, would directly determine whether loss of [SLC8A2](/details-gene/6543) leads to aberrant insulin release kinetics. **Therapeutic Potential:** As a cell-surface ion transporter, [SLC8A2](/details-gene/6543) is a druggable target. However, its crucial role in the central nervous system presents a significant challenge for therapeutic development due to the high risk of on-target neurological side effects. Small molecule modulators could theoretically be developed to either enhance or inhibit its activity. Activation of [SLC8A2](/details-gene/6543) could be beneficial in conditions of calcium overload, such as after ischemic injury, by promoting calcium extrusion. Conversely, targeted inhibition might be explored to modulate hormone secretion or neuronal firing. Any therapeutic strategy would likely require highly specific allosteric modulators or cell-type-specific delivery systems to minimize adverse effects.

Genular Protein ID: 3923501449

Symbol: NAC2_HUMAN

Name: Sodium/calcium exchanger 2

UniProtKB Accession Codes:

Q9UPR5 B4DYQ9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 28 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 43 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 Rhea 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10470851

Title: Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10470851

DOI: 10.1093/dnares/6.3.197

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 23506867

Title: The SLC8 gene family of sodium-calcium exchangers (NCX) - structure, function, and regulation in health and disease.

PubMed ID: 23506867

DOI: 10.1016/j.mam.2012.07.003

PubMed ID: 24501278

Title: Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation.

PubMed ID: 24501278

DOI: 10.1093/hmg/ddu056

Sequence Information:

  • Length: 921
  • Mass: 100368
  • Checksum: 798CDF7E32B9410C
  • Sequence:
    • MAPLALVGVT LLLAAPPCSG AATPTPSLPP PPANDSDTST GGCQGSYRCQ PGVLLPVWEP 
DDPSLGDKAA RAVVYFVAMV YMFLGVSIIA DRFMAAIEVI TSKEKEITIT KANGETSVGT 
VRIWNETVSN LTLMALGSSA PEILLSVIEV CGHNFQAGEL GPGTIVGSAA FNMFVVIAVC 
IYVIPAGESR KIKHLRVFFV TASWSIFAYV WLYLILAVFS PGVVQVWEAL LTLVFFPVCV 
VFAWMADKRL LFYKYVYKRY RTDPRSGIII GAEGDPPKSI ELDGTFVGAE APGELGGLGP 
GPAEARELDA SRREVIQILK DLKQKHPDKD LEQLVGIANY YALLHQQKSR AFYRIQATRL 
MTGAGNVLRR HAADASRRAA PAEGAGEDED DGASRIFFEP SLYHCLENCG SVLLSVTCQG 
GEGNSTFYVD YRTEDGSAKA GSDYEYSEGT LVFKPGETQK ELRIGIIDDD IFEEDEHFFV 
RLLNLRVGDA QGMFEPDGGG RPKGRLVAPL LATVTILDDD HAGIFSFQDR LLHVSECMGT 
VDVRVVRSSG ARGTVRLPYR TVDGTARGGG VHYEDACGEL EFGDDETMKT LQVKIVDDEE 
YEKKDNFFIE LGQPQWLKRG ISALLLNQGD GDRKLTAEEE EARRIAEMGK PVLGENCRLE 
VIIEESYDFK NTVDKLIKKT NLALVIGTHS WREQFLEAIT VSAGDEEEEE DGSREERLPS 
CFDYVMHFLT VFWKVLFACV PPTEYCHGWA CFGVSILVIG LLTALIGDLA SHFGCTVGLK 
DSVNAVVFVA LGTSIPDTFA SKVAALQDQC ADASIGNVTG SNAVNVFLGL GVAWSVAAVY 
WAVQGRPFEV RTGTLAFSVT LFTVFAFVGI AVLLYRRRPH IGGELGGPRG PKLATTALFL 
GLWLLYILFA SLEAYCHIRG F