SLC8A3

solute carrier family 8 member A3, the group of Solute carrier family 8

Basic information

Region (hg38): 14:70044214-70189480

Links

ENSG00000100678 ∙ NCBI:6547 ∙ OMIM:607991 ∙ HGNC:11070 ∙ Uniprot:P57103 ∙ 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 SLC8A3 gene.

• Inborn genetic diseases (44 variants)
• not provided (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC8A3 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				3	4	7
missense			43	2	2	47
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	43	5	6

Variants in SLC8A3

This is a list of pathogenic ClinVar variants found in the SLC8A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-70045982-T-C		not specified	Uncertain significance (May 04, 2022)
14-70045983-G-A			Likely benign (Dec 19, 2017)
14-70046073-G-T		not specified	Uncertain significance (Aug 02, 2021)
14-70046172-C-G			Benign (Dec 31, 2019)
14-70046261-C-T		not specified	Uncertain significance (Nov 18, 2022)
14-70046302-G-C		not specified	Uncertain significance (Oct 12, 2022)
14-70048761-T-C			Uncertain significance (Dec 17, 2020)
14-70048788-C-T		not specified	Uncertain significance (Sep 28, 2022)
14-70048859-A-G		not specified	Uncertain significance (Aug 30, 2021)
14-70048895-A-G		not specified	Uncertain significance (Jul 26, 2022)
14-70048896-C-T		not specified	Uncertain significance (Oct 27, 2022)
14-70048984-G-A			Likely benign (Jan 03, 2019)
14-70049016-C-T		not specified	Uncertain significance (Nov 13, 2023)
14-70049034-C-T		not specified	Uncertain significance (Nov 21, 2022)
14-70051035-A-G		not specified	Uncertain significance (Feb 15, 2023)
14-70051107-T-C		not specified	Uncertain significance (Nov 21, 2022)
14-70052093-G-T		not specified	Uncertain significance (Jun 02, 2023)
14-70052100-T-C		not specified	Uncertain significance (Jul 20, 2022)
14-70055810-A-C		not specified	Uncertain significance (Feb 11, 2022)
14-70055813-G-A		not specified	Likely benign (Aug 10, 2023)
14-70060856-C-A		not specified	Uncertain significance (Jan 31, 2024)
14-70166663-A-C		not specified	Uncertain significance (Jul 14, 2021)
14-70166733-C-T		Malignant tumor of prostate	Uncertain significance (-)
14-70166750-G-A		not specified	Uncertain significance (Apr 12, 2022)
14-70166786-C-G		not specified	Uncertain significance (Dec 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC8A3	protein_coding	protein_coding	ENST00000381269	7	144854

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000734	0.999	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.417	508	535	0.949	0.0000293	6106
Missense in Polyphen		181	219.14	0.82596		2431
Synonymous	-0.108	211	209	1.01	0.0000119	1874
Loss of Function	3.30	11	30.8	0.358	0.00000172	353

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000554	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.0000554	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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, both in muscle and in brain. 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. SLC8A3 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In neurons, 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 (By similarity). Required for normal oligodendrocyte differentiation and for normal myelination (PubMed:21959935). Mediates Ca(2+) efflux from mitochondria and contributes to mitochondrial Ca(2+) ion homeostasis (By similarity). {ECO:0000250|UniProtKB:S4R2P9, ECO:0000269|PubMed:21959935}.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;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;Mitochondrial calcium ion transport;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.157

Intolerance Scores

• loftool: 0.388
• rvis_EVS: -1.06
• rvis_percentile_EVS: 7.55

Haploinsufficiency Scores

• pHI: 0.823
• hipred: Y
• hipred_score: 0.652
• ghis: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.311

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc8a3
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: hematopoietic progenitor cell differentiation;ion transport;mitochondrial calcium ion transmembrane transport;cellular calcium ion homeostasis;cell communication;learning;memory;regulation of skeletal muscle contraction;telencephalon development;sodium ion transmembrane transport;myelination;oligodendrocyte differentiation;mitochondrial calcium ion homeostasis;regulation of postsynaptic membrane potential;long-term synaptic potentiation;calcium ion transmembrane transport;cellular response to cAMP;cellular response to hypoxia;calcium ion import across plasma membrane;regulation of cardiac conduction;calcium ion export across plasma membrane
• Cellular component: mitochondrial outer membrane;endoplasmic reticulum membrane;microtubule;plasma membrane;integral component of plasma membrane;sarcoplasm;cell junction;intrinsic component of plasma membrane;neuromuscular junction;sarcolemma;dendritic spine;perikaryon;perinuclear region of cytoplasm;integral component of postsynaptic membrane
• Molecular function: calcium:sodium antiporter activity;calmodulin binding;metal ion binding;ion antiporter activity involved in regulation of postsynaptic membrane potential