SLC12A1

solute carrier family 12 member 1, the group of Solute carrier family 12

Basic information

Region (hg38): 15:48178438-48304078

Links

ENSG00000074803 ∙ NCBI:6557 ∙ OMIM:600839 ∙ HGNC:10910 ∙ Uniprot:Q13621 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• antenatal Bartter syndrome (Supportive), mode of inheritance: AR
• Bartter disease type 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bartter syndrome, antenatal, type 1	AR	Renal	Sequelae can be lethal; Medical treatment of manifestations including hypokalemia and metabolic alkalosis (eg, with KCl supplementation, NSAIDs), as well as related findings such as nephrocalcinosis, can be beneficial	Renal	3863906; 8457138; 3888887; 8640224; 9355073; 19513753; 20219833

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC12A1 gene.

• not_provided (727 variants)
• Bartter_disease_type_1 (306 variants)
• Inborn_genetic_diseases (126 variants)
• SLC12A1-related_disorder (24 variants)
• not_specified (23 variants)
• Bartter_syndrome (12 variants)
• Nephrocalcinosis (3 variants)
• Nephrolithiasis (3 variants)
• Familial_hypokalemia-hypomagnesemia (3 variants)
• Juvenile_polyposis_syndrome (2 variants)
• See_cases (2 variants)
• Bartter_disease_type_3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC12A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000338.3. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	235	3	245
missense	1	24	323	18	2	368
nonsense	27	8	2			37
start loss						0
frameshift	25	17	3			45
splice donor/acceptor (+/-2bp)	2	33	2			37
Total	55	82	337	253	5

Highest pathogenic variant AF is 0.0000527616

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC12A1	protein_coding	protein_coding	ENST00000396577	26	112415

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.68e-17	0.984	125465	0	128	125593	0.000510

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.16	502	581	0.864	0.0000291	7188
Missense in Polyphen		212	269.91	0.78545		3340
Synonymous	-0.603	222	211	1.05	0.0000119	2076
Loss of Function	2.63	35	56.3	0.621	0.00000280	700

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00133	0.00132
Ashkenazi Jewish	0.0000995	0.0000993
East Asian	0.000437	0.000435
Finnish	0.000464	0.000462
European (Non-Finnish)	0.000462	0.000449
Middle Eastern	0.000437	0.000435
South Asian	0.000473	0.000457
Other	0.000826	0.000816

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
• 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: 0.105

Intolerance Scores

• loftool: 0.0632
• rvis_EVS: -0.83
• rvis_percentile_EVS: 11.49

Haploinsufficiency Scores

• pHI: 0.559
• hipred: Y
• hipred_score: 0.651
• ghis: 0.435

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.171

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc12a1
• Phenotype: immune system phenotype; renal/urinary system phenotype; skeleton 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); hematopoietic 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

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