KCNN2 (potassium calcium-activated channel subfamily N member 2)

Gene

• Entrez ID: 3781
• Gene name: Potassium calcium-activated channel subfamily N member 2
• Gene symbol: KCNN2
• Synonyms (NCBI Gene): DYT34, KCa2.2, NEDMAB, SK2, SKCA2, SKCa 2, hSK2
• Chromosome: 5
• Chromosome location: 5q22.3
• Summary: Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1554086554	TAT>-	Likely-pathogenic	Coding sequence variant, inframe deletion, intron variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029340	hsa-miR-26b-5p	Microarray	19088304

Transcription factors

Transcription factor	Regulation	Reference
ERG	Unknown	23185447

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005242	Function	Inward rectifier potassium channel activity	IDA	12382077
GO:0005242	Function	Inward rectifier potassium channel activity	IEA
GO:0005515	Function	Protein binding	IPI	19815520, 24951510
GO:0005516	Function	Calmodulin binding	IBA
GO:0005516	Function	Calmodulin binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	19815520, 27165696
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	NAS	10991935
GO:0006813	Process	Potassium ion transport	TAS	9287325, 10991935, 13679367, 33242881
GO:0009986	Component	Cell surface	IDA	19815520
GO:0015269	Function	Calcium-activated potassium channel activity	IDA	17110593
GO:0015269	Function	Calcium-activated potassium channel activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	NAS	10991935
GO:0016286	Function	Small conductance calcium-activated potassium channel activity	IBA
GO:0016286	Function	Small conductance calcium-activated potassium channel activity	IDA	9287325, 10991935, 12382077, 13679367, 24951510, 33242881
GO:0016286	Function	Small conductance calcium-activated potassium channel activity	IEA
GO:0016286	Function	Small conductance calcium-activated potassium channel activity	IMP	19815520
GO:0016286	Function	Small conductance calcium-activated potassium channel activity	ISS	19139040
GO:0016286	Function	Small conductance calcium-activated potassium channel activity	TAS	10991935
GO:0019904	Function	Protein domain specific binding	IPI	19815520
GO:0030018	Component	Z disc	IEA
GO:0030018	Component	Z disc	ISS	24951510
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0042803	Function	Protein homodimerization activity	IPI	17110593
GO:0043025	Component	Neuronal cell body	IBA
GO:0043197	Component	Dendritic spine	IBA
GO:0051393	Function	Alpha-actinin binding	IPI	17110593
GO:0071805	Process	Potassium ion transmembrane transport	IBA
GO:0071805	Process	Potassium ion transmembrane transport	IDA	12382077, 17110593, 24951510
GO:0071805	Process	Potassium ion transmembrane transport	ISS	19139040
GO:0098914	Process	Membrane repolarization during atrial cardiac muscle cell action potential	ISS	19139040
GO:1901379	Process	Regulation of potassium ion transmembrane transport	IDA	17110593

Other IDs

• MIM: 605879
• HGNC: 6291
• e!Ensembl: ENSG00000080709

Protein

• UniProt ID: Q9H2S1
• Protein name: Small conductance calcium-activated potassium channel protein 2 (SK2) (SKCa 2) (SKCa2) (KCa2.2)
• Protein function: Small conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calcium all
• PDB: 5V02, 5WBX, 5WC5, 6ALE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03530	SK_channel	120 → 233	Calcium-activated SK potassium channel	Family
  PF07885	Ion_trans_2	304 → 398	Ion channel	Family
  PF02888	CaMBD	412 → 486	Calmodulin binding domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in atrial myocytes (at protein level) (PubMed:13679367). Widely expressed. {ECO:0000269|PubMed:13679367}.
• Sequence:

  MSSCRYNGGVMRPLSNLSASRRNLHEMDSEAQPLQPPASVGGGGGASSPSAAAAAAAAVS
  SSAPEIVVSKPEHNNSNNLALYGTGGGGSTGGGGGGGGSGHGSSSGTKSSKKKNQNIGYK
  LGHRRALFEKRKRLSDYALIFGMFGIVVMVIETELSWGAYDKASLYSLALKCLISLSTII
  LLGLIIVYHAREIQLFMVDNGADDWRIAMTYERIFFICLEILVCAIHPIPGNYTFTWTAR
  LAFSYAPSTTTADVDIILSIPMFLRLYLIARVMLLHSKLFTDASSRSIGALNKINFNTRF
  VMKTLMTICPGTVLLVFSISLWIIAAWTVRACERYHDQQDVTSNFLGAMWLISITFLSIG
  YGDMVPNTYCGKGVCLLTGIMGAGCTALVVAVVARKLELTKAEKHVHNFMMDTQLTKRVK
  NAAANVLRETWLIYKNTKLVKKIDHAKVRKHQRKFLQAIHQLRSVKMEQRKLNDQANTLV
  DLAKTQNIMYDMISDLNERSEDFEKRIVTLETKLETLIGSIHALPGLISQTIRQQQRDFI
  EAQMESYDKHVTYNAERSRSSSRRRRSSSTAPPTSSESS

• Sequence length: 579

Pathways

KEGG:

Serotonergic synapse
Insulin secretion
GnRH secretion
Bile secretion

Reactome:

Ca2+ activated K+ 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
Autistic behavior	Pathogenic; Likely pathogenic	rs774833524, rs1758880343, rs1761282515, rs1761282724, rs1761822790, rs1761825165	RCV001201168 RCV001201169 RCV001201172 RCV001201173 RCV001201174 RCV001201175	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Cerebellar ataxia	Pathogenic; Likely pathogenic	rs1758879579, rs1761282515, rs1747594790	RCV001201167 RCV001201172 RCV001201176	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Dyskinesia	Pathogenic	rs1747594790	RCV001201176	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Dystonia 34, myoclonic	Pathogenic	rs2531643196	RCV004006243	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Likely pathogenic; Pathogenic	rs1554086554, rs774833524, rs1758879579, rs1758880343, rs1761282515, rs1761282724, rs1761822790, rs1747594790, rs1761825165	RCV001201170 RCV001201168 RCV001201167 RCV001201169 RCV001201172 RCV001201173 RCV001201174 RCV001201176 RCV001201175	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intellectual disability	Likely pathogenic	rs1758880343, rs1761282515	RCV001201169 RCV001201172	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
KCNN2-related disorder	Likely pathogenic; Pathogenic	rs1554086554	RCV003424193	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mild intellectual disability	Pathogenic; Likely pathogenic	rs1758879579, rs1761282724, rs1747594790	RCV001201167 RCV001201173 RCV001201176	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Moderate intellectual disability	Pathogenic; Likely pathogenic	rs1761822790, rs1761825165	RCV001201174 RCV001201175	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Motor tics	Pathogenic; Likely pathogenic	rs774833524, rs1758880343	RCV001201168 RCV001201169	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder	Likely pathogenic	rs2150115220	RCV002273226	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities	Likely pathogenic; Pathogenic	rs2531615369, rs2531643196, rs1554086554, rs774833524, rs1758880343, rs1761282515, rs1747594790, rs1761825165	RCV003223507 RCV004006243 RCV005626121 RCV001822865 RCV001822866 RCV003224884 RCV001822867 RCV003151833	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Seizure	Likely pathogenic; Pathogenic	rs1761282724, rs1761825165	RCV001201173 RCV001201175	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe intellectual disability	Pathogenic	rs774833524	RCV001201168	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARRHYTHMIAS, CARDIAC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bradykinesia	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, HEPATOCELLULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIAC ARREST	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIAC ARRHYTHMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOEMBOLIC STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOVASCULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ANEURYSM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSKINETIC SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EDEMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART SEPTAL DEFECT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE IDIOPATHIC ARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KCNN2-related Neurodevelopmental movement disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 1 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alveolar rhabdomyosarcoma	Alveolar Rhabdomyosarcoma	BEFREE	23185447		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	26830138		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	27442679, 29545482	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	GWASCAT_DG	28416818, 29892015, 30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	CTD_human_DG	29892015, 30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cognition Disorders	Cognition disorder	Pubtator	37510285	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Aneurysm	Coronary Aneurysm	BEFREE	23677057		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Aneurysm	Coronary Aneurysm	GWASCAT_DG	23677057		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	30545309		★☆☆☆☆ Found in Text Mining only
Dystonia	Dystonia	Pubtator	35106185	Associate	★☆☆☆☆ Found in Text Mining only
Essential Tremor	Essential tremor	Pubtator	37510285	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	16817201	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	27442679	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	CTD_human_DG	28284560		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	CLINVAR_DG	10200319, 11181977, 15184377, 15190101, 15194823, 15234350, 15937479, 17329434, 18604572, 19075508, 19515965, 20553876, 21923633, 21942705, 22072564, 22495311, 23430260, 24434522, 25917818, 26166566, 27048600		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement disorder	Pubtator	35106185	Associate	★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	BEFREE	23677057		★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	GWASDB_DG	23677057		★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	GWASCAT_DG	23677057		★☆☆☆☆ Found in Text Mining only
Myoclonic dystonia	Myoclonic dystonia	Pubtator	35106185	Associate	★☆☆☆☆ Found in Text Mining only
Paroxysmal atrial fibrillation	Paroxysmal atrial fibrillation	CTD_human_DG	29892015, 30061737		★☆☆☆☆ Found in Text Mining only
Sarcoma	Sarcoma	Pubtator	34294833	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	31374203		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tremor	Tremor	Pubtator	37510285	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Fibrillation	Ventricular fibrillation	Pubtator	27442679	Associate	★☆☆☆☆ Found in Text Mining only