SLC8B1

Summary

SLC8B1 (solute carrier family 8 member B1, HGNC:26175) is a protein-coding gene on chromosome 12q24.13, encoding Mitochondrial sodium/calcium exchanger protein (Q6J4K2). Mitochondrial sodium/calcium antiporter that mediates sodium-dependent calcium efflux from mitochondrion, by mediating the exchange of 3 sodium ions per 1 calcium ion.

SLC24A6 belongs to a family of potassium-dependent sodium/calcium exchangers that maintain cellular calcium homeostasis through the electrogenic countertransport of 4 sodium ions for 1 calcium ion and 1 potassium ion (Cai and Lytton, 2004 [PubMed 14625281]).

Source: NCBI Gene 80024 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_001358345

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26175
Approved symbol	SLC8B1
Name	solute carrier family 8 member B1
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22233, NCKX6, NCLX
Ensembl gene	ENSG00000089060
Ensembl biotype	protein_coding
OMIM	609841
Entrez	80024

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000202831, ENST00000546737, ENST00000548186, ENST00000548477, ENST00000548518, ENST00000549069, ENST00000549181, ENST00000549372, ENST00000549605, ENST00000550047, ENST00000550672, ENST00000551230, ENST00000552014, ENST00000552565, ENST00000552613, ENST00000553238, ENST00000680972, ENST00000900295

RefSeq mRNA: 3 — MANE Select: NM_001358345 NM_001330466, NM_001358345, NM_024959

CCDS: CCDS31909, CCDS81744

Canonical transcript exons

ENST00000680972 — 16 exons

Exon	Start	End
ENSE00003477480	113321056	113321108
ENSE00003483800	113307691	113307844
ENSE00003517232	113320850	113320907
ENSE00003553812	113306495	113306575
ENSE00003600168	113304321	113304385
ENSE00003608945	113316526	113316656
ENSE00003609679	113310234	113310355
ENSE00003635617	113320581	113320686
ENSE00003651656	113318964	113319071
ENSE00003665321	113315335	113315476
ENSE00003666193	113332723	113332960
ENSE00003694048	113316942	113317001
ENSE00003786432	113321196	113321348
ENSE00003787150	113320331	113320498
ENSE00003914631	113334443	113335109
ENSE00003914706	113298771	113299974

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2681 / max 668.0896, expressed in 1796 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133358	16.2681	1796

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland cortex	UBERON:0035825	97.59	gold quality
right adrenal gland	UBERON:0001233	97.48	gold quality
right adrenal gland cortex	UBERON:0035827	97.44	gold quality
left adrenal gland	UBERON:0001234	97.31	gold quality
left ovary	UBERON:0002119	96.51	gold quality
adrenal cortex	UBERON:0001235	96.33	gold quality
adrenal gland	UBERON:0002369	96.26	gold quality
right ovary	UBERON:0002118	96.04	gold quality
adrenal tissue	UBERON:0018303	93.56	gold quality
ovary	UBERON:0000992	91.97	gold quality
spleen	UBERON:0002106	91.71	gold quality
mucosa of transverse colon	UBERON:0004991	91.42	gold quality
sural nerve	UBERON:0015488	91.39	gold quality
metanephros cortex	UBERON:0010533	91.09	gold quality
granulocyte	CL:0000094	91.08	gold quality
lower esophagus mucosa	UBERON:0035834	90.30	gold quality
colonic epithelium	UBERON:0000397	90.20	gold quality
apex of heart	UBERON:0002098	90.15	gold quality
blood	UBERON:0000178	89.99	gold quality
endocervix	UBERON:0000458	89.52	gold quality
transverse colon	UBERON:0001157	89.23	gold quality
skin of leg	UBERON:0001511	89.22	gold quality
body of pancreas	UBERON:0001150	89.14	gold quality
upper lobe of left lung	UBERON:0008952	89.03	gold quality
mucosa of stomach	UBERON:0001199	89.02	gold quality
minor salivary gland	UBERON:0001830	89.02	gold quality
monocyte	CL:0000576	88.83	gold quality
leukocyte	CL:0000738	88.82	gold quality
mononuclear cell	CL:0000842	88.80	gold quality
right lobe of liver	UBERON:0001114	88.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting SLC8B1, 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-12121	99.99	66.64	255
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6076	98.61	65.69	637
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-634	97.74	67.11	818
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-885-3P	95.14	63.08	448

Literature-anchored findings (GeneRIF, showing 13)

• NCKX6 is a novel member of the Na+/Ca2+ exchanger superfamily (PMID:14625281)
• NCLX catalyzes active Li(+)/Ca(2+) exchange. (PMID:15060069)
• NCLX, but not LETM1, mediates Ca(2+) extrusion from mitochondria. By controlling the duration of matrix Ca(2+) elevations, NCLX contributes to the regulation of NAD(P)H production and to the conversion of Ca(2+) signals into redox changes. (PMID:24898248)
• It has been shown that the propagation of the TRPV1-induced cytosolic calcium and sodium fluxes into mitochondria is dependent on coordinated activity of NCLX and MCU. (PMID:27627464)
• Store-operated Ca(2+) entry activates a mitochondrial redox transient which is dependent on NCLX and is required for preventing Orai1 inactivation through oxidation of a critical cysteine (Cys195) in the third transmembrane helix of Orai1. (PMID:28219928)
• mild fluctuations in mitochondrial membrane potential, which do not affect Ca(2+) influx, are sufficient to strongly regulate NCLX. (PMID:30566870)
• The unique crosstalk of this exchanger with Na(+) and Ca(2+) signaling pathways in the cell membrane and the endoplasmic reticulum, and with protein kinases that posttranslationally modulate NCLX activity. (PMID:30658153)
• Dichotomous role of the human mitochondrial Na(+)/Ca2(+)/Li(+) exchanger NCLX in colorectal cancer growth and metastasis. (PMID:32914752)
• Aberrant activity of mitochondrial NCLX is linked to impaired synaptic transmission and is associated with mental retardation. (PMID:34079053)
• Disrupted expression of mitochondrial NCLX sensitizes neuroglial networks to excitotoxic stimuli and renders synaptic activity toxic. (PMID:34942149)
• Physiological and Pathophysiological Roles of Mitochondrial Na(+)-Ca(2+) Exchanger, NCLX, in Hearts. (PMID:34944520)
• Spatial and Functional Crosstalk between the Mitochondrial Na(+)-Ca(2+) Exchanger NCLX and the Sarcoplasmic Reticulum Ca(2+) Pump SERCA in Cardiomyocytes. (PMID:35887296)
• CKII Control of Axonal Plasticity Is Mediated by Mitochondrial Ca[2+] via Mitochondrial NCLX. (PMID:36552754)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc8b1	ENSDARG00000105584
mus_musculus	Slc8b1	ENSMUSG00000032754
rattus_norvegicus	Slc8b1	ENSRNOG00000001383
drosophila_melanogaster	CG12376	FBGN0033323
drosophila_melanogaster	CG14744	FBGN0033324
drosophila_melanogaster	CG14743	FBGN0033326
drosophila_melanogaster	CG13223	FBGN0033599
drosophila_melanogaster	CG5348	FBGN0034156
caenorhabditis_elegans		WBGENE00003571
caenorhabditis_elegans		WBGENE00003572
caenorhabditis_elegans		WBGENE00003573
caenorhabditis_elegans		WBGENE00003574

Protein

Protein identifiers

Mitochondrial sodium/calcium exchanger protein — Q6J4K2 (reviewed: Q6J4K2)

Alternative names: Na(+)/K(+)/Ca(2+)-exchange protein 6, Sodium/calcium exchanger protein, mitochondrial, Sodium/potassium/calcium exchanger 6, Solute carrier family 24 member 6, Solute carrier family 8 member B1

All UniProt accessions (8): Q6J4K2, A0A0B4J252, F8VR99, F8VTU4, F8VW44, F8VWW9, F8W134, H0YI75

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial sodium/calcium antiporter that mediates sodium-dependent calcium efflux from mitochondrion, by mediating the exchange of 3 sodium ions per 1 calcium ion. Plays a central role in mitochondrial calcium homeostasis by mediating mitochondrial calcium extrusion: calcium efflux is essential for mitochondrial function and cell survival, notably in cardiomyocytes. Regulates rates of glucose-dependent insulin secretion in pancreatic beta-cells during the first phase of insulin secretion: acts by mediating efflux of calcium from mitochondrion, thereby affecting cytoplasmic calcium responses. Required for store-operated Ca(2+) entry (SOCE) and Ca(2+) release-activated Ca(2+) (CRAC) channel regulation: sodium transport by SLC8B1 leads to promote calcium-shuttling that modulates mitochondrial redox status, thereby regulating SOCE activity. Involved in B-lymphocyte chemotaxis. Able to transport Ca(2+) in exchange of either Li(+) or Na(+), explaining how Li(+) catalyzes Ca(2+) exchange. In contrast to other members of the family its function is independent of K(+).

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Present in pancreatic beta-cells (at protein level).

Post-translational modifications. Phosphorylation at Ser-258 by PKA prevents calcium overload.

Activity regulation. Inhibited by the sodium/calcium exchanger inhibitor CGP-37157. Strongly inhibited by zinc.

Similarity. Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6J4K2-1	1	yes
Q6J4K2-2	2, S-NCLX

RefSeq proteins (3): NP_001317395, NP_001345274, NP_079235 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004837	NaCa_Exmemb	Domain
IPR044880	NCX_ion-bd_dom_sf	Homologous_superfamily
IPR051359	CaCA_antiporter	Family

Pfam: PF01699

Catalyzed reactions (Rhea), 2 shown:

• Ca(2+)(in) + 3 Na(+)(out) = Ca(2+)(out) + 3 Na(+)(in) (RHEA:69955)
• 3 Li(+)(out) + Ca(2+)(in) = 3 Li(+)(in) + Ca(2+)(out) (RHEA:72631)

UniProt features (50 total): topological domain 14, transmembrane region 13, mutagenesis site 13, sequence conflict 3, sequence variant 2, signal peptide 1, chain 1, modified residue 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6J4K2-F1	80.91	0.45

Functional residue map

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

Post-translational modifications (1): 258

Glycosylation sites (1): 60

Mutagenesis-validated functional residues (13):

Position	Phenotype
149	lithium-selective; displays reduced calcium:sodium antiporter activity while retaining almost normal calcium:lithium ant
152	lithium-selective; displays markedly reduced calcium:sodium antiporter activity while retaining almost normal calcium:li
153	lithium-selective; displays markedly reduced calcium:sodium antiporter activity while retaining almost normal calcium:li
176	non-selective; displays similar reduction of calcium:sodium and calcium:lithium antiporter activities.
258	abolished ability to prevent calcium overload.
258	phosphomimetic mutant; prevents calcium overload.
467	has no effect on calcium:sodium antiporter activity.
467	lithium-selective; displays markedly reduced calcium:sodium antiporter activity while retaining normal calcium:lithium a
468	lithium-selective; displays markedly reduced calcium:sodium antiporter activity while retaining almost normal calcium:li
471	sodium-selective; has little effect on calcium:sodium antiporter activity while displaying markedly reduced calcium:lith
471	non-selective; displays reduction of both calcium:sodium and calcium:lithium antiporter activities.
494	lithium-selective; displays markedly reduced calcium:sodium antiporter activity while retaining almost normal calcium:li
498	non-selective; displays similar reduction of calcium:sodium and calcium:lithium antiporter activities.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-425561	Sodium/Calcium exchangers
R-HSA-8949215	Mitochondrial calcium ion transport
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 206 (showing top): GOBP_CELL_CHEMOTAXIS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INSULIN_SECRETION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_MITOCHONDRIAL_CALCIUM_ION_HOMEOSTASIS, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_TAXIS, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_LEUKOCYTE_MIGRATION

GO Biological Process (16): monoatomic ion transport (GO:0006811), mitochondrial calcium ion transmembrane transport (GO:0006851), intracellular calcium ion homeostasis (GO:0006874), glucose homeostasis (GO:0042593), regulation of insulin secretion (GO:0050796), regulation of cytosolic calcium ion concentration (GO:0051480), mitochondrial calcium ion homeostasis (GO:0051560), regulation of cardiac muscle cell membrane potential (GO:0086036), calcium export from the mitochondrion (GO:0099093), regulation of lymphocyte chemotaxis (GO:1901623), regulation of store-operated calcium entry (GO:2001256), sodium ion transport (GO:0006814), calcium ion transport (GO:0006816), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (6): calcium:sodium antiporter activity (GO:0005432), calcium:monoatomic cation antiporter activity (GO:0015368), protein homodimerization activity (GO:0042803), calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential (GO:0086038), antiporter activity (GO:0015297), identical protein binding (GO:0042802)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), plasma membrane (GO:0005886), membrane (GO:0016020), mitochondrial crista (GO:0030061), mitochondrial membrane (GO:0031966), sarcolemma (GO:0042383)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transport of small molecules	2
Metal ion SLC transporters	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
intracellular calcium ion homeostasis	2
mitochondrion	2
metal ion transport	2
monoatomic cation transmembrane transport	2
cellular anatomical structure	2
calcium ion transmembrane transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
carbohydrate homeostasis	1
insulin secretion	1
regulation of protein secretion	1
regulation of peptide hormone secretion	1
regulation of membrane potential	1
mitochondrial calcium ion transmembrane transport	1
release of sequestered calcium ion into cytosol	1
regulation of leukocyte chemotaxis	1
lymphocyte chemotaxis	1
regulation of lymphocyte migration	1
store-operated calcium entry	1
regulation of calcium ion transport	1
sodium ion transport	1
cellular process	1
calcium ion transport	1
sodium ion transmembrane transporter activity	1
calcium:monoatomic cation antiporter activity	1
calcium ion transmembrane transporter activity	1
metal cation:monoatomic cation antiporter activity	1
identical protein binding	1
protein dimerization activity	1
calcium:sodium antiporter activity	1
regulation of cardiac muscle cell membrane potential	1
secondary active transmembrane transporter activity	1
protein binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC8B1	LETM1	O95202	864
SLC8B1	MICU1	Q9BPX6	806
SLC8B1	MCU	Q8NE86	789
SLC8B1	MICU2	Q8IYU8	775
SLC8B1	MCUR1	Q96AQ8	706
SLC8B1	MICU3	Q86XE3	667
SLC8B1	SMDT1	Q9H4I9	661
SLC8B1	SLC8A3	P57103	653
SLC8B1	SLC8A2	Q9UPR5	650
SLC8B1	MCUB	Q9NWR8	649
SLC8B1	ITPR3	Q14573	587
SLC8B1	PPIF	P30405	585
SLC8B1	ITPR1	Q14643	574
SLC8B1	VDAC1	P21796	571
SLC8B1	SLC8A1	P32418	568

IntAct

3 interactions, top by confidence:

A	B	Type	Score
	NPC1	psi-mi:“MI:0914”(association)	0.350
SLC8B1	GAA	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): SLC8B1 (Affinity Capture-RNA), SLC8B1 (Affinity Capture-RNA), SLC8B1 (Affinity Capture-RNA), SLC8B1 (Affinity Capture-RNA), CDC5L (Affinity Capture-MS), CSTF3 (Affinity Capture-MS), CYFIP2 (Affinity Capture-MS), EIF2S3 (Affinity Capture-MS), EIF4H (Affinity Capture-MS), ELP4 (Affinity Capture-MS), GAA (Affinity Capture-MS), HCFC1 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP4 (Affinity Capture-MS), NCKAP1 (Affinity Capture-MS)

ESM2 similar proteins: A1L272, A4FV75, A5A6S6, A6QL92, B0BMY1, B8AF63, F1NXU8, O54902, O80605, P49281, P49282, P57057, P57758, Q17QZ3, Q28HR4, Q3TIT8, Q5EAL3, Q5F383, Q5F3N0, Q5R6J3, Q5R839, Q5RD30, Q5ZJX0, Q640L2, Q6DHU1, Q6DIV6, Q6IR74, Q6J4K2, Q6NTJ7, Q6P499, Q6PF45, Q6YK44, Q6ZP29, Q8BGN5, Q8BJA2, Q8BXA5, Q8C4N4, Q8IVJ1, Q8NA29, Q8NCC5

Diamond homologs: F1NXU8, O04034, O60721, Q49SH1, Q6AXS0, Q6J4K2, Q71RS6, Q925Q3, Q9FKP1, Q9FKP2, O46383, O54701, P34322, P45394, P48768, Q0ZAI3, Q28139, Q2R041, Q6H641, Q8BUN9, Q8CGQ8, Q8K596, Q8NFF2, Q91WD8, Q99PD7, Q9EPQ0, Q9HC58, Q9IAL7, Q9IAL8, Q9QZM6, Q9U6A0, Q9UI40, Q9UPR5, Q9VDG5, O16242, P34315, P47144, Q8C261, Q9VN12, P57103

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	SLC8B1	phosphorylation
PKA	“up-regulates activity”	SLC8B1	phosphorylation
SLC8B1	“up-regulates quantity”	calcium(2+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2933 predictions. Top by Δscore:

Variant	Effect	Δscore
12:113306493:A:AC	donor_gain	1.0000
12:113306494:C:CC	donor_gain	1.0000
12:113307692:T:TA	donor_gain	1.0000
12:113310352:CCAT:C	acceptor_gain	1.0000
12:113310353:CAT:C	acceptor_gain	1.0000
12:113310353:CATC:C	acceptor_gain	1.0000
12:113310356:C:CC	acceptor_gain	1.0000
12:113315326:GATAC:G	donor_loss	1.0000
12:113315327:ATAC:A	donor_loss	1.0000
12:113315328:TACT:T	donor_loss	1.0000
12:113315329:ACTC:A	donor_loss	1.0000
12:113315331:TCA:T	donor_loss	1.0000
12:113315332:CACAG:C	donor_loss	1.0000
12:113315333:A:AC	donor_gain	1.0000
12:113315333:ACAGG:A	donor_loss	1.0000
12:113315334:C:CG	donor_gain	1.0000
12:113315334:CAG:C	donor_gain	1.0000
12:113315334:CAGG:C	donor_gain	1.0000
12:113315334:CAGGT:C	donor_gain	1.0000
12:113315472:GGCAG:G	acceptor_gain	1.0000
12:113315473:GCAG:G	acceptor_gain	1.0000
12:113315474:CAG:C	acceptor_gain	1.0000
12:113315474:CAGC:C	acceptor_gain	1.0000
12:113315475:AG:A	acceptor_gain	1.0000
12:113315477:C:CC	acceptor_gain	1.0000
12:113315477:C:CG	acceptor_loss	1.0000
12:113316521:CCTAC:C	donor_loss	1.0000
12:113316522:CTACC:C	donor_loss	1.0000
12:113316523:TACCT:T	donor_loss	1.0000
12:113316524:ACC:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008973 (12:113310541 G>C), RS1000159972 (12:113329172 C>T), RS1000170698 (12:113298814 A>T), RS1000256390 (12:113316084 C>T), RS1000286385 (12:113322336 G>A,C), RS1000413194 (12:113328543 C>T), RS1000592848 (12:113333854 A>G), RS1000803261 (12:113300737 A>T), RS1000807704 (12:113314827 T>G), RS1000820563 (12:113312397 G>C), RS1000831884 (12:113312659 C>T), RS1000888464 (12:113328724 C>G), RS1000935195 (12:113327271 C>T), RS1001064739 (12:113317995 A>G), RS1001126800 (12:113308986 T>C)

Disease associations

OMIM: gene MIM:609841 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001738_6	Response to fenofibrate (adiponectin levels)	5.000000e-08
GCST005951_2	Body mass index	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3763001 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC24 family of sodium/potassium/calcium exchangers

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
CGP-37157	Inhibition	5.8	pIC50

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.80	IC50	1600	nM	CHEMBL1495071

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2-one	1277316: Inhibition of mitochondrial sodium/calcium exchanger (unknown origin)	ic50	1.6000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression, increases abundance	1
nickel sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3766982	Binding	Inhibition of mitochondrial sodium/calcium exchanger (unknown origin)	Neuroprotective profile of pyridothiazepines with blocking activity of the mitochondrial Na(+)/Ca(2+) exchanger. — Eur J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4QN	HCT116-SLC8B1-KO-c5	Cancer cell line	Male
CVCL_D4QP	HCT116-SLC8B1-KO-c6	Cancer cell line	Male
CVCL_D8VG	Ubigene HCT 116 SLC8B1 KO	Cancer cell line	Male
CVCL_TP17	HAP1 SLC8B1 (-) 1	Cancer cell line	Male
CVCL_XT38	HAP1 SLC8B1 (-) 2	Cancer cell line	Male
CVCL_XT39	HAP1 SLC8B1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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