KCNA4 (potassium voltage-gated channel subfamily A member 4)

Gene

• Entrez ID: 3739
• Gene name: Potassium voltage-gated channel subfamily A member 4
• Gene symbol: KCNA4
• Synonyms (NCBI Gene): HBK4, HK1, HPCN2, HUKII, KCNA4L, KCNA8, KV1.4, MCIDDS, PCN2
• Chromosome: 11
• Chromosome location: 11p14.1
• Summary: Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, e

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs779101828	C>G,T	Pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017281	hsa-miR-335-5p	Microarray	18185580
MIRT657071	hsa-miR-8485	HITS-CLIP	23824327
MIRT657070	hsa-miR-329-3p	HITS-CLIP	23824327
MIRT657069	hsa-miR-362-3p	HITS-CLIP	23824327
MIRT657068	hsa-miR-603	HITS-CLIP	23824327
MIRT657067	hsa-miR-4789-3p	HITS-CLIP	23824327
MIRT657066	hsa-miR-3941	HITS-CLIP	23824327
MIRT657065	hsa-miR-3682-5p	HITS-CLIP	23824327
MIRT657064	hsa-miR-4789-5p	HITS-CLIP	23824327
MIRT657063	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT657071	hsa-miR-8485	HITS-CLIP	23824327
MIRT657070	hsa-miR-329-3p	HITS-CLIP	23824327
MIRT657069	hsa-miR-362-3p	HITS-CLIP	23824327
MIRT657068	hsa-miR-603	HITS-CLIP	23824327
MIRT657067	hsa-miR-4789-3p	HITS-CLIP	23824327
MIRT657066	hsa-miR-3941	HITS-CLIP	23824327
MIRT657065	hsa-miR-3682-5p	HITS-CLIP	23824327
MIRT657064	hsa-miR-4789-5p	HITS-CLIP	23824327
MIRT657063	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT1080251	hsa-miR-329	CLIP-seq
MIRT1080252	hsa-miR-4639-3p	CLIP-seq
MIRT2251834	hsa-miR-1301	CLIP-seq
MIRT1080251	hsa-miR-329	CLIP-seq
MIRT2251835	hsa-miR-377	CLIP-seq
MIRT2251836	hsa-miR-5047	CLIP-seq
MIRT2251837	hsa-miR-548n	CLIP-seq
MIRT2251838	hsa-miR-548t	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001508	Process	Action potential	IBA
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005249	Function	Voltage-gated potassium channel activity	IDA	8495559
GO:0005249	Function	Voltage-gated potassium channel activity	IEA
GO:0005249	Function	Voltage-gated potassium channel activity	IMP	19912772, 27582084
GO:0005249	Function	Voltage-gated potassium channel activity	TAS	2001794
GO:0005251	Function	Delayed rectifier potassium channel activity	IBA
GO:0005267	Function	Potassium channel activity	IEA
GO:0005515	Function	Protein binding	IPI	7477295, 9786987, 11937501, 16169070, 19968958, 24550280, 32296183, 33961781
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IMP	8495559, 19912772
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006813	Process	Potassium ion transport	IEA
GO:0006813	Process	Potassium ion transport	TAS	2001794
GO:0008076	Component	Voltage-gated potassium channel complex	IBA
GO:0008076	Component	Voltage-gated potassium channel complex	IEA
GO:0008076	Component	Voltage-gated potassium channel complex	IMP	8495559
GO:0008076	Component	Voltage-gated potassium channel complex	ISS
GO:0008076	Component	Voltage-gated potassium channel complex	TAS	2001794
GO:0016020	Component	Membrane	IBA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	ISS
GO:0030424	Component	Axon	IBA
GO:0030424	Component	Axon	IEA
GO:0030424	Component	Axon	ISS
GO:0030955	Function	Potassium ion binding	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034702	Component	Monoatomic ion channel complex	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043194	Component	Axon initial segment	IEA
GO:0043197	Component	Dendritic spine	IBA
GO:0051260	Process	Protein homooligomerization	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0071805	Process	Potassium ion transmembrane transport	IBA
GO:0071805	Process	Potassium ion transmembrane transport	IDA	8495559
GO:0071805	Process	Potassium ion transmembrane transport	IEA
GO:0071805	Process	Potassium ion transmembrane transport	IMP	19912772
GO:0099505	Process	Regulation of presynaptic membrane potential	IEA
GO:0099508	Function	Voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IEA

Other IDs

• MIM: 176266
• HGNC: 6222
• e!Ensembl: ENSG00000182255

Protein

• UniProt ID: P22459
• Protein name: Potassium voltage-gated channel subfamily A member 4 (HPCN2) (Voltage-gated K(+) channel HuKII) (Voltage-gated potassium channel HBK4) (Voltage-gated potassium channel HK1) (Voltage-gated potassium channel subunit Kv1.4)
• Protein function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channe
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07941	K_channel_TID	1 → 75	Potassium channel Kv1.4 tandem inactivation domain	Family
  PF02214	BTB_2	178 → 269	BTB/POZ domain	Domain
  PF00520	Ion_trans	306 → 571	Ion transport protein	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in brain, and at lower levels in the testis, lung, kidney, colon and heart (PubMed:27582084). Detected in heart ventricle. {ECO:0000269|PubMed:2001794, ECO:0000269|PubMed:27582084}.
• Sequence:

  MEVAMVSAESSGCNSHMPYGYAAQARARERERLAHSRAAAAAAVAAATAAVEGSGGSGGG
  SHHHHQSRGACTSHDPQSSRGSRRRRRQRSEKKKAHYRQSSFPHCSDLMPSGSEEKILRE
  LSEEEEDEEEEEEEEEEGRFYYSEDDHGDECSYTDLLPQDEGGGGYSSVRYSDCCERVVI
  NVSGLRFETQMKTLAQFPETLLGDPEKRTQYFDPLRNEYFFDRNRPSFDAILYYYQSGGR
  LKRPVNVPFDIFTEEVKFYQLGEEALLKFREDEGFVREEEDRALPENEFKKQIWLLFEYP
  ESSSPARGIAIVSVLVILISIVIFCLETLPEFRDDRDLVMALSAGGHGGLLNDTSAPHLE
  NSGHTIFNDPFFIVETVCIVWFSFEFVVRCFACPSQALFFKNIMNIIDIVSILPYFITLG
  TDLAQQQGGGNGQQQQAMSFAILRIIRLVRVFRIFKLSRHSKGLQILGHTLRASMRELGL
  LIFFLFIGVILFSSAVYFAEADEPTTHFQSIPDAFWWAVVTMTTVGYGDMKPITVGGKIV
  GSLCAIAGVLTIALPVPVIVSNFNYFYHRETENEEQTQLTQNAVSCPYLPSNLLKKFRSS
  TSSSLGDKSEYLEMEEGVKESLCAKEEKCQGKGDDSETDKNNCSNAKAVETDV

• Sequence length: 653

Pathways

KEGG:

Cortisol synthesis and secretion
Cushing syndrome

Reactome:

Voltage gated Potassium 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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum	Uncertain significance	ClinVar ClinVar, Disgenet, GenCC, HPO ClinVar, Disgenet, GenCC, HPO ClinVar, Disgenet, GenCC, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PREECLAMPSIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arrhythmias Cardiac	Cardiac arrhythmias	Pubtator	28575239	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	24578158	Associate	★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital long QT syndrome	Congenital Long QT Syndrome	BEFREE	14661677, 16253929		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	30944034		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	35439054	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	33498463	Associate	★☆☆☆☆ Found in Text Mining only
Graves Ophthalmopathy	Graves ophthalmopathy	Pubtator	32908802	Associate	★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	Pubtator	34226506	Associate	★☆☆☆☆ Found in Text Mining only
Long QT Syndrome	Long QT Syndrome	BEFREE	10483966, 10984545, 11113008, 17470695, 9386136		★☆☆☆☆ Found in Text Mining only
Long QT Syndrome	Long qt syndrome	Pubtator	9307251	Associate	★☆☆☆☆ Found in Text Mining only
Long QT Syndrome 1	Long QT Syndrome	BEFREE	9386136, 9641694		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	1879830		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
MICROCEPHALY, CATARACTS, IMPAIRED INTELLECTUAL DEVELOPMENT, AND DYSTONIA WITH ABNORMAL STRIATUM	Microcystic meningioma	UNIPROT_DG	27582084		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Pulmonary Arterial Hypertension	Pulmonary arterial hypertension	Pubtator	34349187	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	30944034		★☆☆☆☆ Found in Text Mining only
Romano-Ward Syndrome	Romano-Ward Syndrome	BEFREE	9641694		★☆☆☆☆ Found in Text Mining only
Torsades de Pointes	Torsades de Pointes	BEFREE	16253929, 29456831		★☆☆☆☆ Found in Text Mining only
Ventricular Fibrillation	Ventricular Fibrillation	BEFREE	29395134		★☆☆☆☆ Found in Text Mining only