SLC8A2

Summary

SLC8A2 (solute carrier family 8 member A2, HGNC:11069) is a protein-coding gene on chromosome 19q13.32, encoding Sodium/calcium exchanger 2 (Q9UPR5). Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes.

Predicted to enable calcium:monoatomic cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration and calcium:sodium antiporter activity. Predicted to be involved in several processes, including learning or memory; monoatomic cation transmembrane transport; and regulation of short-term neuronal synaptic plasticity. Predicted to act upstream of or within several processes, including modulation of chemical synaptic transmission; regulation of action potential firing pattern; and response to ischemia. Located in presynapse. Biomarker of Alzheimer’s disease.

Source: NCBI Gene 6543 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_015063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11069
Approved symbol	SLC8A2
Name	solute carrier family 8 member A2
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	NCX2, KIAA1087
Ensembl gene	ENSG00000118160
Ensembl biotype	protein_coding
OMIM	601901
Entrez	6543

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000236877, ENST00000539381, ENST00000542837, ENST00000594353, ENST00000597014, ENST00000600576, ENST00000601757, ENST00000885652, ENST00000953455

RefSeq mRNA: 1 — MANE Select: NM_015063 NM_015063

CCDS: CCDS33065

Canonical transcript exons

ENST00000236877 — 10 exons

Exon	Start	End
ENSE00000952970	47447809	47448231
ENSE00000952974	47465729	47466419
ENSE00002533035	47428017	47430465
ENSE00003088142	47471789	47471893
ENSE00003491200	47437462	47437561
ENSE00003529578	47437849	47437973
ENSE00003551877	47441337	47441440
ENSE00003622341	47441169	47441186
ENSE00003658104	47456930	47457594
ENSE00003741174	47432167	47432445

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 97.57.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5591 / max 354.8451, expressed in 286 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181766	3.0817	257
181765	1.0916	192
181767	0.7990	77
181768	0.5453	66
208878	0.0416	26

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.57	gold quality
cerebellar hemisphere	UBERON:0002245	97.51	gold quality
cerebellar cortex	UBERON:0002129	97.46	gold quality
cerebellum	UBERON:0002037	96.75	gold quality
paraflocculus	UBERON:0005351	95.80	gold quality
prefrontal cortex	UBERON:0000451	94.64	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.06	gold quality
cortical plate	UBERON:0005343	93.06	gold quality
frontal cortex	UBERON:0001870	92.33	gold quality
right frontal lobe	UBERON:0002810	92.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.78	gold quality
frontal pole	UBERON:0002795	91.21	gold quality
neocortex	UBERON:0001950	90.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.20	gold quality
cerebral cortex	UBERON:0000956	89.29	gold quality
superior frontal gyrus	UBERON:0002661	88.91	gold quality
cingulate cortex	UBERON:0003027	88.83	gold quality
anterior cingulate cortex	UBERON:0009835	88.77	gold quality
cerebellar vermis	UBERON:0004720	87.94	gold quality
postcentral gyrus	UBERON:0002581	86.24	gold quality
telencephalon	UBERON:0001893	85.84	gold quality
entorhinal cortex	UBERON:0002728	85.49	gold quality
orbitofrontal cortex	UBERON:0004167	85.41	gold quality
Ammon’s horn	UBERON:0001954	85.25	gold quality
brain	UBERON:0000955	84.91	gold quality
CA1 field of hippocampus	UBERON:0003881	84.58	silver quality
amygdala	UBERON:0001876	84.56	gold quality
forebrain	UBERON:0001890	84.51	gold quality
temporal lobe	UBERON:0001871	84.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.39

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ATP2B1	Unknown
RCAN3	Unknown

Upstream regulators (CollecTRI, top): APP, ESR1

miRNA regulators (miRDB)

142 targeting SLC8A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 13)

• plasma membrane Na+/Ca2+ exchangers have inhibitory interactions with the 14-3-3 proteins (PMID:16679322)
• The aim of this study was to investigate if NCX2 might be a tumour suppressor gene involved in glioma. Results indicate that DNA methylation may play a key role in the transcriptional silencing of NCX2. (PMID:20132488)
• Results demonstrate a selective regulation of NCX1, NCX2 and NCX3 isoforms in Alzheimer’s disease cortex, specifically in terminals containing amyloid-beta. (PMID:21382638)
• Data suggest that NCX-mediated Ca(2+) fluxes normally exist in human ASM (potentially contributing to rapid Ca(2+) fluxes), and contribute to enhanced Ca(2+) regulation in airway inflammation. (PMID:21858195)
• NCX isoforms (NCX2, NCX3) contribute to mitochondrial Na(+)/Ca(2+) exchange in human DAergic neurons and may act downstream of PINK1 in the prevention of neurodegeneration by m[Ca(2+)] accumulation. (PMID:23224884)
• the large cytosolic loop of NCX1, NCX2, and NCX3 is involved in acquisition of immunosuppressive drug specificity (PMID:23224887)
• 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. (PMID:23224890)
• SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma (PMID:29047259)
• Structure-Dynamic Coupling Through Ca(2+)-Binding Regulatory Domains of Mammalian NCX Isoform/Splice Variants (PMID:29594857)
• Methylation on SLC8A2 is associated with the development of anti-tuberculosis drug-induced liver injury. (PMID:31247120)
• miR-206 Reduces the Severity of Motor Neuron Degeneration in the Facial Nuclei of the Brainstem in a Mouse Model of SMA. (PMID:32075715)
• The downregulation of NCXs is positively correlated with the prognosis of stage II-IV colon cancer. (PMID:34127021)
• NCX2 Regulates Intracellular Calcium Homeostasis and Translocation of HIF-1alpha into the Nucleus to Inhibit Glioma Invasion. (PMID:36334237)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc8a2a	ENSDARG00000008912
danio_rerio	slc8a2b	ENSDARG00000100592
mus_musculus	Slc8a2	ENSMUSG00000030376
rattus_norvegicus	Slc8a2	ENSRNOG00000001492
caenorhabditis_elegans		WBGENE00003568

Paralogs (7): SLC8A3 (ENSG00000100678), FRAS1 (ENSG00000138759), FREM2 (ENSG00000150893), ADGRV1 (ENSG00000164199), FREM1 (ENSG00000164946), SLC8A1 (ENSG00000183023), FREM3 (ENSG00000183090)

Protein

Protein identifiers

Sodium/calcium exchanger 2 — Q9UPR5 (reviewed: Q9UPR5)

Alternative names: Na(+)/Ca(2+)-exchange protein 2, Solute carrier family 8 member 2

All UniProt accessions (4): Q9UPR5, F5H6L7, M0R1Z4, M0R211

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes. Contributes to cellular Ca(2+) homeostasis in excitable cells. Contributes to the rapid decrease of cytoplasmic Ca(2+) levels back to baseline after neuronal activation, and thereby contributes to modulate synaptic plasticity, learning and memory. Plays a role in regulating urinary Ca(2+) and Na(+) excretion.

Subcellular location. Cell membrane. Basolateral cell membrane. Perikaryon. Cell projection. Dendrite. Dendritic spine.

Activity regulation. Calcium transport is down-regulated by Na(+) and stimulated by Ca(2+).

Domain organisation. The cytoplasmic Calx-beta domains bind the regulatory Ca(2+). The first Calx-beta domain can bind up to four Ca(2+) ions. The second domain can bind another two Ca(2+) ions that are essential for calcium-regulated ion exchange.

Similarity. Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.

RefSeq proteins (1): NP_055878* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003644	Calx_beta	Domain
IPR004836	Na_Ca_Ex	Family
IPR004837	NaCa_Exmemb	Domain
IPR032452	Na_Ca_Ex_C-exten	Domain
IPR038081	CalX-like_sf	Homologous_superfamily
IPR044880	NCX_ion-bd_dom_sf	Homologous_superfamily
IPR051171	CaCA	Family

Pfam: PF01699, PF03160, PF16494

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) + 3 Na(+)(out) = Ca(2+)(out) + 3 Na(+)(in) (RHEA:69955)

UniProt features (62 total): binding site 26, topological domain 12, transmembrane region 11, repeat 2, domain 2, region of interest 2, glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPR5-F1	77.22	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (26): 407; 407; 407; 443; 443; 468; 469; 469; 469; 469; 471; 473 …

Post-translational modifications (1): 622

Glycosylation sites (2): 34, 817

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-418359	Reduction of cytosolic Ca++ levels
R-HSA-425561	Sodium/Calcium exchangers
R-HSA-5578775	Ion homeostasis
R-HSA-109582	Hemostasis
R-HSA-382551	Transport of small molecules
R-HSA-397014	Muscle contraction
R-HSA-418346	Platelet homeostasis
R-HSA-418360	Platelet calcium homeostasis
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 225 (showing top): GOBP_MEMORY, ACTACCT_MIR196A_MIR196B, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_SHORT_TERM_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GGGCATT_MIR365, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL

GO Biological Process (28): response to ischemia (GO:0002931), monoatomic ion transport (GO:0006811), intracellular calcium ion homeostasis (GO:0006874), cell communication (GO:0007154), learning or memory (GO:0007611), learning (GO:0007612), memory (GO:0007613), regulation of gene expression (GO:0010468), sodium ion transmembrane transport (GO:0035725), regulation of short-term neuronal synaptic plasticity (GO:0048172), synapse organization (GO:0050808), cognition (GO:0050890), regulation of cytosolic calcium ion concentration (GO:0051480), long-term synaptic potentiation (GO:0060291), neuron cellular homeostasis (GO:0070050), calcium ion transmembrane transport (GO:0070588), calcium ion import across plasma membrane (GO:0098703), modulation of excitatory postsynaptic potential (GO:0098815), regulation of action potential firing pattern (GO:0099608), regulation of calcineurin-mediated signaling (GO:0106056), transport across blood-brain barrier (GO:0150104), positive regulation of intracellular signal transduction (GO:1902533), regulation of cardiac conduction (GO:1903779), calcium ion export across plasma membrane (GO:1990034), sodium ion transport (GO:0006814), calcium ion transport (GO:0006816), transmembrane transport (GO:0055085), regulation of postsynaptic cytosolic calcium ion concentration (GO:0099566)

GO Molecular Function (7): calcium:sodium antiporter activity (GO:0005432), calmodulin binding (GO:0005516), sodium ion transmembrane transporter activity (GO:0015081), calcium ion transmembrane transporter activity (GO:0015085), metal ion binding (GO:0046872), calcium:monoatomic cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration (GO:1905060), antiporter activity (GO:0015297)

GO Cellular Component (16): plasma membrane (GO:0005886), postsynaptic density (GO:0014069), basolateral plasma membrane (GO:0016323), axon (GO:0030424), dendrite (GO:0030425), sarcolemma (GO:0042383), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), perikaryon (GO:0043204), axon terminus (GO:0043679), synapse (GO:0045202), presynapse (GO:0098793), postsynapse (GO:0098794), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Platelet calcium homeostasis	1
Metal ion SLC transporters	1
Cardiac conduction	1
Hemostasis	1
Platelet homeostasis	1
Transport of small molecules	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
learning or memory	2
monoatomic cation transmembrane transport	2
calcium:monoatomic cation antiporter activity	2
metal ion transmembrane transporter activity	2
neuron projection	2
plasma membrane	2
synapse	2
response to stress	1
transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
cellular process	1
behavior	1
cognition	1
gene expression	1
regulation of macromolecule biosynthetic process	1
sodium ion transport	1
regulation of neuronal synaptic plasticity	1
cell junction organization	1
nervous system process	1
intracellular calcium ion homeostasis	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
cellular homeostasis	1
calcium ion transport	1
calcium ion import	1
calcium ion transmembrane import into cytosol	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
regulation of signal transduction	1
regulation of nervous system process	1
regulation of membrane potential	1
modulation of chemical synaptic transmission	1
excitatory postsynaptic potential	1
spike train	1
regulation of action potential	1
regulation of calcium-mediated signaling	1
calcineurin-mediated signaling	1
sodium ion transmembrane transporter activity	1

Protein interactions and networks

STRING

1752 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC8A2	SLC8B1	Q6J4K2	650
SLC8A2	ADAMTSL2	Q86TH1	577
SLC8A2	SLC6A1	P30531	568
SLC8A2	COL8A2	P25067	523
SLC8A2	ATP2B4	P23634	503
SLC8A2	COL16A1	Q07092	502
SLC8A2	ADAMTS10	Q9H324	502
SLC8A2	ATP2B1	P20020	500
SLC8A2	ATP2B2	Q01814	472
SLC8A2	ATP2B3	Q16720	461
SLC8A2	SV2B	Q7L1I2	454
SLC8A2	CAMK2A	Q9UQM7	448
SLC8A2	KCNH3	Q9ULD8	427
SLC8A2	ITPKA	P23677	425
SLC8A2	SLC17A7	Q9P2U7	412

IntAct

13 interactions, top by confidence:

A	B	Type	Score
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC8A2	GPR35	psi-mi:“MI:0915”(physical association)	0.370
SLC8A2	GPR37	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC8A3	GPD2	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
S1PR3	STXBP3	psi-mi:“MI:0914”(association)	0.350
SYP	TMEM223	psi-mi:“MI:0914”(association)	0.350
UPK2	IFT56	psi-mi:“MI:0914”(association)	0.350
ZDHHC11	NRP1	psi-mi:“MI:0914”(association)	0.350
SLC8A2	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): SLC8A2 (Affinity Capture-MS), SLC8A2 (Affinity Capture-MS), SLC8A2 (Two-hybrid), SLC8A2 (Two-hybrid), SLC8A2 (Affinity Capture-RNA), SLC8A2 (Affinity Capture-MS), SLC8A2 (Affinity Capture-MS), SLC8A2 (Affinity Capture-MS), ACTG1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), CLTC (Affinity Capture-MS), CORO1C (Affinity Capture-MS), DBN1 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IQZ2, A0A125YSC7, A0A125YZH9, A0A1D3TGZ2, A0A1G4GWI6, A0A384J983, A0A384JSZ0, A0A679KXN5, A2WV32, C4LWU5, C8ZJM1, G4YM00, G4Z2L3, G5EBM5, O76819, P0CD92, P14773, P16393, P20715, P21441, P48768, P54960, P57103, P70549, P84737, Q0IWF3, Q28614, Q4P333, Q5JN63, Q6WNG7, Q6ZXT3, Q76L34, Q7EYH7, Q8K596, Q8S9F2, Q8VIH3, Q93Z13, Q9AT74, Q9ATN0, Q9ERH8

Diamond homologs: B8K1V7, O22252, O54701, P23685, P32418, P48765, P48766, P48767, P48768, P57103, P70414, P70549, Q01728, Q2R041, Q6H641, Q8BUN9, Q8CGQ8, Q8K596, Q8NFF2, Q99PD7, Q9EPQ0, Q9HC58, Q9UI40, Q9UPR5, Q9VDG5, Q9VN12, S4R2P9, O60721, O46383, P45394, P87122, Q0ZAI3, Q28139, Q49SH1, Q57556, Q71RS6, Q8C261, Q8TPA6, Q91WD8, Q9IAL7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

98 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1635 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47430461:CGTGT:C	acceptor_gain	1.0000
19:47430462:GTGT:G	acceptor_gain	1.0000
19:47430463:TGT:T	acceptor_gain	1.0000
19:47430463:TGTC:T	acceptor_loss	1.0000
19:47430464:GT:G	acceptor_gain	1.0000
19:47430464:GTCT:G	acceptor_loss	1.0000
19:47430466:C:CC	acceptor_gain	1.0000
19:47430466:CT:C	acceptor_loss	1.0000
19:47437971:CCC:C	acceptor_gain	1.0000
19:47437972:CCC:C	acceptor_gain	1.0000
19:47441353:AAG:A	donor_gain	1.0000
19:47471783:TCTTA:T	donor_loss	1.0000
19:47471784:CTTA:C	donor_loss	1.0000
19:47471785:TTA:T	donor_loss	1.0000
19:47471786:TA:T	donor_loss	1.0000
19:47471787:A:AT	donor_loss	1.0000
19:47471788:C:CG	donor_loss	1.0000
19:47432214:T:TA	donor_gain	0.9900
19:47437970:TCCC:T	acceptor_gain	0.9900
19:47437971:CCCC:C	acceptor_gain	0.9900
19:47437972:CC:C	acceptor_gain	0.9900
19:47437973:CC:C	acceptor_gain	0.9900
19:47437973:CCTGC:C	acceptor_loss	0.9900
19:47441187:C:CC	acceptor_gain	0.9900
19:47441331:CCTCA:C	donor_loss	0.9900
19:47441332:CTCA:C	donor_loss	0.9900
19:47441333:TCA:T	donor_loss	0.9900
19:47441334:CACCT:C	donor_loss	0.9900
19:47441335:A:T	donor_loss	0.9900
19:47441336:C:G	donor_loss	0.9900

AlphaMissense

5977 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47432359:A:G	W733R	1.000
19:47432359:A:T	W733R	1.000
19:47437501:A:G	W691R	1.000
19:47437501:A:T	W691R	1.000
19:47437545:A:G	L676P	1.000
19:47437849:C:A	K670N	1.000
19:47437849:C:G	K670N	1.000
19:47437853:A:C	F669C	1.000
19:47437853:A:G	F669S	1.000
19:47437871:A:T	I663N	1.000
19:47441378:A:T	I609N	1.000
19:47441384:A:G	F607S	1.000
19:47441403:A:G	Y601H	1.000
19:47441420:A:T	I595K	1.000
19:47447827:A:G	F582S	1.000
19:47447897:A:C	Y559D	1.000
19:47447933:G:T	R547S	1.000
19:47447998:A:G	F525S	1.000
19:47448004:C:T	G523D	1.000
19:47448013:T:A	D520V	1.000
19:47448013:T:C	D520G	1.000
19:47448013:T:G	D520A	1.000
19:47448016:T:A	D519V	1.000
19:47448016:T:G	D519A	1.000
19:47448018:G:C	D518E	1.000
19:47448018:G:T	D518E	1.000
19:47448019:T:A	D518V	1.000
19:47448019:T:G	D518A	1.000
19:47448020:C:G	D518H	1.000
19:47448025:A:C	I516S	1.000

dbSNP variants (sampled 300 via entrez): RS1000057688 (19:47443039 C>T), RS1000154369 (19:47442234 A>G), RS1000202611 (19:47472181 GC>G), RS1000284176 (19:47437241 A>G), RS1000334946 (19:47448505 A>G), RS1000366170 (19:47449123 G>T), RS1000378549 (19:47430733 T>C,G), RS1000441081 (19:47472030 G>A), RS1000462680 (19:47444810 G>A), RS1000545017 (19:47438257 A>G), RS1000614776 (19:47436976 G>C), RS1000719189 (19:47436812 G>A), RS1000726143 (19:47473203 C>T), RS1000743055 (19:47464915 A>C,T), RS1000792195 (19:47471680 C>A)

Disease associations

OMIM: gene MIM:601901 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006138_43	Resting-state electroencephalogram vigilance	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC8 family of sodium/calcium exchangers

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
neurounina-1	Activation	8.77	pEC50
SAR296968	Inhibition	7.64	pIC50

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
sodium arsenite	affects methylation, increases expression	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Triclosan	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4QL	HCT116-SLC8A2-KO-c4	Cancer cell line	Male
CVCL_D4QM	HCT116-SLC8A2-KO-c6	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.