SLC8A1

solute carrier family 8 member A1, the group of Solute carrier family 8

Basic information

Region (hg38): 2:40097269-40611053

Previous symbols: [ "NCX1" ]

Links

ENSG00000183023 ∙ NCBI:6546 ∙ OMIM:182305 ∙ HGNC:11068 ∙ Uniprot:P32418 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC8A1 gene.

• Inborn genetic diseases (26 variants)
• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC8A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	4	9
missense			26	2		28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	26	7	4

Variants in SLC8A1

This is a list of pathogenic ClinVar variants found in the SLC8A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-40115284-A-G		not specified	Uncertain significance (Oct 26, 2022)
2-40115329-C-A		not specified	Uncertain significance (Sep 07, 2022)
2-40115345-T-C		not specified	Uncertain significance (Feb 02, 2024)
2-40115354-G-A		not specified	Uncertain significance (Sep 17, 2021)
2-40115390-G-T			Benign (Jun 26, 2018)
2-40115405-C-T		not specified	Uncertain significance (Sep 20, 2023)
2-40115460-G-T			Benign (Dec 31, 2019)
2-40115467-G-A		not specified	Uncertain significance (May 27, 2022)
2-40115488-T-A		not specified	Uncertain significance (Feb 14, 2023)
2-40115550-C-T			Benign (Aug 08, 2018)
2-40115591-A-G		not specified	Uncertain significance (Apr 19, 2023)
2-40139474-G-C		not specified	Uncertain significance (Jan 10, 2023)
2-40139495-G-A			Likely benign (May 14, 2018)
2-40139572-C-T		not specified	Uncertain significance (Dec 19, 2023)
2-40139617-C-A		not specified	Uncertain significance (Jan 17, 2024)
2-40139663-G-C		not specified	Uncertain significance (Aug 16, 2021)
2-40160778-G-A			Likely benign (Mar 29, 2018)
2-40160780-T-C		not specified	Uncertain significance (May 27, 2022)
2-40160859-A-T			Likely benign (Jul 01, 2022)
2-40164934-G-A		not specified	Uncertain significance (Oct 05, 2021)
2-40164983-G-A			Likely benign (Jun 26, 2018)
2-40177826-C-T			Likely benign (Aug 01, 2022)
2-40178403-C-G		not specified	Uncertain significance (Aug 08, 2023)
2-40178486-T-C		not specified	Uncertain significance (Oct 13, 2023)
2-40428505-A-C		not specified	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC8A1	protein_coding	protein_coding	ENST00000403092	10	513784

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00430	125699	0	10	125709	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.20	395	538	0.734	0.0000281	6409
Missense in Polyphen		87	230.42	0.37757		2705
Synonymous	-3.02	259	204	1.27	0.0000114	1935
Loss of Function	4.74	4	33.7	0.119	0.00000165	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000623	0.0000616
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000656	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)- dependent cellular processes (PubMed:1374913, PubMed:11241183, PubMed:1476165). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions. {ECO:0000250|UniProtKB:P70414, ECO:0000269|PubMed:11241183, ECO:0000269|PubMed:1374913, ECO:0000269|PubMed:1476165}.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Mineral absorption - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Arrhythmogenic Right Ventricular Cardiomyopathy;Vitamin D Receptor Pathway;Myometrial Relaxation and Contraction Pathways;VEGFA-VEGFR2 Signaling Pathway;Calcium Regulation in the Cardiac Cell;Ion homeostasis;Sodium/Calcium exchangers;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Cardiac conduction;Muscle contraction;Hemostasis;Reduction of cytosolic Ca++ levels;Platelet calcium homeostasis;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.362
• rvis_EVS: -1.15
• rvis_percentile_EVS: 6.29

Haploinsufficiency Scores

• pHI: 0.392
• hipred: Y
• hipred_score: 0.768
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.658

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc8a1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype

Zebrafish Information Network

• Gene name: slc8a1a
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: regulation of the force of heart contraction;regulation of heart rate;regulation of sodium ion transport;ion transport;cellular sodium ion homeostasis;muscle contraction;response to glucose;regulation of cell communication by electrical coupling;positive regulation of fibroblast migration;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;regulation of cardiac muscle contraction by calcium ion signaling;vascular smooth muscle contraction;telencephalon development;positive regulation of bone mineralization;response to ATP;sodium ion transmembrane transport;response to immobilization stress;response to muscle stretch;sodium ion export across plasma membrane;response to hydrogen peroxide;relaxation of smooth muscle;negative regulation of cytosolic calcium ion concentration;cardiac muscle cell development;calcium ion homeostasis;relaxation of cardiac muscle;cardiac muscle contraction;regulation of postsynaptic membrane potential;cytosolic calcium ion transport;calcium ion transport into cytosol;calcium ion import;calcium ion transmembrane transport;cellular response to caffeine;cellular response to cAMP;cellular response to hypoxia;membrane depolarization during cardiac muscle cell action potential;cell communication by electrical coupling involved in cardiac conduction;sodium ion import across plasma membrane;positive regulation of the force of heart contraction;regulation of cardiac conduction
• Cellular component: nucleoplasm;mitochondrion;microtubule;plasma membrane;integral component of plasma membrane;intercalated disc;Z disc;T-tubule;sarcolemma;dendritic spine;dendritic shaft;integral component of postsynaptic membrane
• Molecular function: calcium:sodium antiporter activity;calcium ion binding;protein binding;calmodulin binding;cytoskeletal protein binding;ankyrin binding;ion channel binding;ion antiporter activity involved in regulation of postsynaptic membrane potential