CLCNKA (chloride voltage-gated channel Ka)

Gene

• Entrez ID: 1187
• Gene name: Chloride voltage-gated channel Ka
• Gene symbol: CLCNKA
• Synonyms (NCBI Gene): CLCK1, ClC-K1, hClC-Ka
• Chromosome: 1
• Chromosome location: 1p36.13
• Summary: This gene is a member of the CLC family of voltage-gated chloride channels. The encoded protein is predicted to have 12 transmembrane domains, and requires a beta subunit called barttin to form a functional channel. It is thought to function in salt reabs

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121909137	G>C,T	Pathogenic	Missense variant, intron variant, coding sequence variant
rs121909138	C>G,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs1557458426	G>T	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT894890	hsa-miR-1292	CLIP-seq
MIRT894891	hsa-miR-3192	CLIP-seq
MIRT894892	hsa-miR-4314	CLIP-seq
MIRT894893	hsa-miR-4471	CLIP-seq
MIRT894894	hsa-miR-4646-5p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
KLF15	Unknown	10982849;11473619
MAZ	Unknown	10982849;11473619

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005247	Function	Voltage-gated chloride channel activity	IBA
GO:0005247	Function	Voltage-gated chloride channel activity	IEA
GO:0005247	Function	Voltage-gated chloride channel activity	TAS	8041726
GO:0005254	Function	Chloride channel activity	IDA	12111250
GO:0005254	Function	Chloride channel activity	IEA
GO:0005515	Function	Protein binding	IPI	12111250, 32296183
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	8041726
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006821	Process	Chloride transport	IBA
GO:0006821	Process	Chloride transport	IEA
GO:0015108	Function	Chloride transmembrane transporter activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016323	Component	Basolateral plasma membrane	IEA
GO:0030321	Process	Transepithelial chloride transport	TAS	8041726
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034707	Component	Chloride channel complex	IEA
GO:0042802	Function	Identical protein binding	IPI	17562318
GO:0046872	Function	Metal ion binding	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0070293	Process	Renal absorption	IEA
GO:0070293	Process	Renal absorption	TAS	8041726
GO:1902476	Process	Chloride transmembrane transport	IEA

Other IDs

• MIM: 602024
• HGNC: 2026
• e!Ensembl: ENSG00000186510

Protein

• UniProt ID: P51800
• Protein name: Chloride channel protein ClC-Ka (Chloride channel Ka) (ClC-K1)
• Protein function: Anion-selective channel permeable to small monovalent anions with ion selectivity for chloride > bromide > nitrate > iodide (PubMed:11734858, PubMed:12111250). Forms a homodimeric channel where each subunit has its own ion conduction pathway. Ma
• PDB: 2PFI
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00654	Voltage_CLC	102 → 514	Voltage gated chloride channel	Family
  PF00571	CBS	547 → 605	CBS domain	Domain

• Sequence:

  MEELVGLREGFSGDPVTLQELWGPCPHIRRAIQGGLEWLKQKVFRLGEDWYFLMTLGVLM
  ALVSYAMNFAIGCVVRAHQWLYREIGDSHLLRYLSWTVYPVALVSFSSGFSQSITPSSGG
  SGIPELKTMLAGVILEDYLDIKNFGAKVVGLSCTLATGSTLFLGKVGPFVHLSVMIAAYL
  GRVRTTTIGEPENKSKQNEMLVAAAAVGVATVFAAPFSGVLFSIEVMSSHFSVRDYWRGF
  FAATCGAFIFRLLAVFNSEQETITSLYKTSFRVDVPFDLPEIFFFVALGGICGVLSCAYL
  FCQRTFLSFIKTNRYSSKLLATSKPVYSALATLLLASITYPPGVGHFLASRLSMKQHLDS
  LFDNHSWALMTQNSSPPWPEELDPQHLWWEWYHPRFTIFGTLAFFLVMKFWMLILATTIP
  MPAGYFMPIFILGAAIGRLLGEALAVAFPEGIVTGGVTNPIMPGGYALAGAAAFSGAVTH
  TISTALLAFELTGQIVHALPVLMAVLAANAIAQSCQPSFYDGTIIVKKLPYLPRILGRNI
  GSHHVRVEHFMNHSITTLAKDTPLEEVVKVVTSTDVTEYPLVESTESQILVGIVQRAQLV
  QALQAEPPSRAPGHQQCLQDILARGCPTEPVTLTLFSETTLHQAQNLFKLLNLQSLFVTS
  RGRAVGCVSWVEMKKAISNLTNPPAPK

• Sequence length: 687

Pathways

Reactome:

Stimuli-sensing channels

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Bartter disease type 4B	Pathogenic; Likely pathogenic	rs121909137, rs121909138, rs2524331289, rs373187796	RCV000008027 RCV000008028 RCV003333332 RCV006250097	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Deafness	Likely pathogenic; Pathogenic	rs1557458426	RCV000679814	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hearing loss, autosomal recessive	Likely pathogenic; Pathogenic	rs1557458426	RCV001291225	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Bartter disease type 3	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARTTER SYNDROME TYPE 4	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARTTER SYNDROME, TYPE 3	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARTTER SYNDROME, TYPE 4B	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARTTER SYNDROME, TYPE 4B, NEONATAL, WITH SENSORINEURAL DEAFNESS	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARGE syndrome	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGESTIVE HEART FAILURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART FAILURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTROPHIC CARDIOMYOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensorineural hearing loss disorder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Bartter Disease	Bartter syndrome	BEFREE	10831588, 18310267, 28334417		★☆☆☆☆ Found in Text Mining only
Bartter Disease	Bartter syndrome	LHGDN	18094726		★☆☆☆☆ Found in Text Mining only
Bartter Syndrome	Bartter syndrome	Pubtator	21937999, 38069401	Associate	★☆☆☆☆ Found in Text Mining only
BARTTER SYNDROME, TYPE 4B	Bartter syndrome	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARTTER SYNDROME, TYPE 4B, NEONATAL, WITH SENSORINEURAL DEAFNESS	Bartter syndrome	UNIPROT_DG	15044642, 18310267		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARTTER SYNDROME, TYPE 4B, NEONATAL, WITH SENSORINEURAL DEAFNESS	Bartter syndrome	GENOMICS_ENGLAND_DG	18310267		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARTTER SYNDROME, TYPE 4B, NEONATAL, WITH SENSORINEURAL DEAFNESS	Bartter syndrome	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathy Dilated	Dilated cardiomyopathy	Pubtator	32916098	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Abnormalities	Cardiovascular abnormalities	Pubtator	24454898	Associate	★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	21248228		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Essential Hypertension	Hypertension	BEFREE	25919862		★☆☆☆☆ Found in Text Mining only
Essential Hypertension	Hypertension	Pubtator	25919862	Associate	★☆☆☆☆ Found in Text Mining only
Gitelman Syndrome	Gitelman syndrome	Pubtator	30999883	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	32725165	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	38069401	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	38069401	Associate	★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	21248228		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heart Failure	Heart failure	Pubtator	21248228, 22499703	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperaldosteronism	Hyperaldosteronism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypernatriuria	Hypernatriuria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	17652939, 28334417	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	BEFREE	17510212, 17652939, 28334417		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	LHGDN	17510212		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	CTD_human_DG	18480177		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypochloremia (disorder)	Hypochloremia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypokalemic hypochloremic metabolic alkalosis	Hypokalemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Infantile Bartter syndrome with sensorineural deafness	Bartter Syndrome With Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nephrogenic Diabetes Insipidus	Nephrogenic Diabetes Insipidus	BEFREE	10831588		★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only