CLCNKA

chloride voltage-gated channel Ka, the group of Chloride voltage-gated channels

Basic information

Region (hg38): 1:16018875-16034050

Links

ENSG00000186510 ∙ NCBI:1187 ∙ OMIM:602024 ∙ HGNC:2026 ∙ Uniprot:P51800 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bartter disease type 4B (Limited), mode of inheritance: AR
• Bartter disease type 4B (Moderate), mode of inheritance: Unknown
• Bartter syndrome type 4 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bartter syndrome, type 4, digenic	AR/Digenic	Audiologic/Otolaryngologic; Renal	Due to renal salt wasting, individuals can present with dehydration and life-threatening hypotension, and electrolyte management can be beneficial; In some forms, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Renal	15044642; 18310267
Digenic inheritance (with CLCNKB) has been described

ClinVar

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

• Inborn_genetic_diseases (98 variants)
• not_provided (60 variants)
• Bartter_disease_type_4B (15 variants)
• not_specified (13 variants)
• Bartter_syndrome_type_4 (2 variants)
• CHARGE_syndrome (1 variants)
• Deafness (1 variants)
• Bartter_disease_type_3 (1 variants)
• Hearing_loss,_autosomal_recessive (1 variants)
• Sensorineural_hearing_loss_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLCNKA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004070.4. 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			2	11	6	19
missense	1	1	101	20	2	125
nonsense	1	2				3
start loss						0
frameshift		1	4			5
splice donor/acceptor (+/-2bp)						0
Total	2	4	107	31	8

Highest pathogenic variant AF is 0.00017162776

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLCNKA	protein_coding	protein_coding	ENST00000331433	19	15176

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.23e-17	0.0777	125198	0	550	125748	0.00219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.334	406	387	1.05	0.0000235	4404
Missense in Polyphen		124	128.3	0.96647		1455
Synonymous	-2.53	210	168	1.25	0.0000114	1443
Loss of Function	1.00	29	35.4	0.818	0.00000179	383

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00974	0.00873
Ashkenazi Jewish	0.00	0.00
East Asian	0.000927	0.000925
Finnish	0.00129	0.00129
European (Non-Finnish)	0.00283	0.00279
Middle Eastern	0.000927	0.000925
South Asian	0.000457	0.000457
Other	0.00229	0.00228

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
• 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;Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.192

Intolerance Scores

• loftool: 0.0670
• rvis_EVS: 1.54
• rvis_percentile_EVS: 95.58

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.139
• ghis: 0.405

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.147

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clcnkb
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism 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); renal/urinary system phenotype

Gene ontology

• Biological process: excretion;ion transmembrane transport;regulation of ion transmembrane transport;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;chloride channel complex
• Molecular function: voltage-gated chloride channel activity;identical protein binding;metal ion binding