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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Bartter disease type 4B	Pathogenic; Likely pathogenic	rs121909137, rs121909138, rs2524331289, rs373187796	RCV000008027 RCV000008028 RCV003333332 RCV006250097
Deafness	Likely pathogenic; Pathogenic	rs1557458426	RCV000679814
Hearing loss, autosomal recessive	Likely pathogenic; Pathogenic	rs1557458426	RCV001291225

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Bartter disease type 3	Conflicting classifications of pathogenicity	rs202069201	RCV000714828
CHARGE syndrome	Conflicting classifications of pathogenicity	rs556704888	RCV005863920
Cholangiocarcinoma	Benign	rs67179509	RCV005923404
Gastric cancer	Benign	rs9442191	RCV005920123
Hepatocellular carcinoma	Benign	rs6669935	RCV005918958
Lung cancer	Benign	rs67179509	RCV005923405
Malignant tumor of esophagus	Conflicting classifications of pathogenicity	rs201309731	RCV005913456
Nonpapillary renal cell carcinoma	Benign	rs9442191	RCV005920121
Ovarian cancer	Benign	rs9442191	RCV005920122
Ovarian serous cystadenocarcinoma	Benign; Conflicting classifications of pathogenicity	rs9442191, rs201309731	RCV005920124 RCV005913457
Sensorineural hearing loss disorder	Conflicting classifications of pathogenicity	rs202069201	RCV001353202
Thymoma	Benign	rs9442191	RCV005920125
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity	rs201309731	RCV005913458
Uterine corpus endometrial carcinoma	Benign; Likely benign	rs140290085	RCV005908624

Associations from Text Mining
Disease Name	Relationship Type	References
Alkalosis	Associate	38069401
Bartter Syndrome	Associate	21937999, 38069401
Cardiomyopathy Dilated	Associate	32916098
Cardiovascular Abnormalities	Associate	24454898
Daneman Davy Mancer syndrome	Associate	38069401
Essential Hypertension	Associate	25919862
Gitelman Syndrome	Associate	30999883
Glioma	Associate	32725165
Hearing Loss	Associate	38069401
Hearing Loss Sensorineural	Associate	38069401
Heart Failure	Associate	21248228, 22499703
Hypertension	Associate	17652939, 28334417
Nonsyndromic sensorineural hearing loss	Associate	21937999, 38069401