SLC12A3

solute carrier family 12 member 3, the group of Solute carrier family 12|MicroRNA protein coding host genes

Basic information

Region (hg38): 16:56865207-56915850

Links

ENSG00000070915OMIM:600968HGNC:10912Uniprot:P55017AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Gitelman syndrome (Strong), mode of inheritance: AR
  • Gitelman syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Gitelman syndromeARCardiovascular; RenalSurveillance for, treatment of, and prevention of electrolyte abnormalities may be beneficial; Individuals with cardiovascular manifestations (eg, arrhythmias such as QTc prolongation) that may warrant interventions have also been describedCardiovascular; Renal5929460; 1436349; 81436349; 16120871; 17000984; 17981812; 22009145
Individuals have been reported with cardiovascular manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC12A3 gene.

  • not_provided (1367 variants)
  • Familial_hypokalemia-hypomagnesemia (685 variants)
  • Inborn_genetic_diseases (132 variants)
  • not_specified (69 variants)
  • SLC12A3-related_disorder (50 variants)
  • Bartter_syndrome (16 variants)
  • Hypokalemia (3 variants)
  • Myalgia (2 variants)
  • Renal_tubular_acidosis (2 variants)
  • Hypermagnesemia (2 variants)
  • Muscle_weakness (2 variants)
  • Renal_tubulopathies (1 variants)
  • Familial_aortopathy (1 variants)
  • Inherited_renal_tubular_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC12A3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001126108.2. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
28
clinvar
488
clinvar
2
clinvar
522
missense
39
clinvar
156
clinvar
349
clinvar
32
clinvar
1
clinvar
577
nonsense
42
clinvar
14
clinvar
1
clinvar
57
start loss
3
3
frameshift
76
clinvar
33
clinvar
2
clinvar
111
splice donor/acceptor (+/-2bp)
32
clinvar
45
clinvar
2
clinvar
79
Total 193 251 382 520 3

Highest pathogenic variant AF is 0.0015203538

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SLC12A3protein_codingprotein_codingENST00000438926 2650644
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
3.03e-320.000091312552202261257480.000899
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.9366826171.110.00003926705
Missense in Polyphen242232.051.04292524
Synonymous-1.082762541.090.00001752052
Loss of Function0.3625052.80.9460.00000269578

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001390.00139
Ashkenazi Jewish0.0001990.000198
East Asian0.001410.00120
Finnish0.000.00
European (Non-Finnish)0.001210.00120
Middle Eastern0.001410.00120
South Asian0.001030.000980
Other0.0006530.000652

dbNSFP

Source: dbNSFP

Function
FUNCTION: Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the proinflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity). {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22009145}.;
Disease
DISEASE: Gitelman syndrome (GTLMNS) [MIM:263800]: An autosomal recessive disorder characterized by hypokalemic alkalosis in combination with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. Patients are often asymptomatic or present transient periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. The phenotype is highly heterogeneous in terms of age at onset and severity. Cardinal features such as hypocalciuria and hypomagnesemia might also change during the life cycle of a given patient. It has overlapping features with Bartter syndrome. {ECO:0000269|PubMed:10616841, ECO:0000269|PubMed:10988270, ECO:0000269|PubMed:11168953, ECO:0000269|PubMed:11940055, ECO:0000269|PubMed:12008755, ECO:0000269|PubMed:12112667, ECO:0000269|PubMed:15069170, ECO:0000269|PubMed:15687331, ECO:0000269|PubMed:16429844, ECO:0000269|PubMed:17654016, ECO:0000269|PubMed:17873326, ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:26099046, ECO:0000269|PubMed:8528245, ECO:0000269|PubMed:8900229, ECO:0000269|PubMed:8954067, ECO:0000269|PubMed:9734597}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Diuretics Pathway, Pharmacodynamics;Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Cystinuria;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Kidney Function;Glucose Transporter Defect (SGLT2);Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;Chlorothiazide Action Pathway;Cation-coupled Chloride cotransporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules (Consensus)

Recessive Scores

pRec
0.278

Intolerance Scores

loftool
0.0228
rvis_EVS
-1.62
rvis_percentile_EVS
2.89

Haploinsufficiency Scores

pHI
0.238
hipred
N
hipred_score
0.251
ghis
0.516

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.911

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Slc12a3
Phenotype
renal/urinary system phenotype; 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); homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name
slc12a3
Affected structure
pronephric duct
Phenotype tag
abnormal
Phenotype quality
morphology

Gene ontology

Biological process
ion transport;sodium ion transport;cell volume homeostasis;sodium ion transmembrane transport;chloride ion homeostasis;potassium ion homeostasis;sodium ion homeostasis;chloride transmembrane transport;potassium ion import across plasma membrane
Cellular component
cytosol;plasma membrane;integral component of plasma membrane;membrane;apical plasma membrane;extracellular exosome
Molecular function
transporter activity;protein binding;sodium:potassium:chloride symporter activity;sodium ion transmembrane transporter activity;sodium:chloride symporter activity;potassium:chloride symporter activity