KCNN4 (potassium calcium-activated channel subfamily N member 4)

Gene

• Entrez ID: 3783
• Gene name: Potassium calcium-activated channel subfamily N member 4
• Gene symbol: KCNN4
• Synonyms: DHS2, IK, IK1, IKCA1, KCA4, KCa3.1, SK4, SKCa4, hIK1, hIKCa1, hKCa4, hSK4
• Chromosome: 19
• Chromosome location: 19q13.31
• Summary: The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded p

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs774455945	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1057519076	C>A,T	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519077	A>T	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001448	hsa-miR-16-5p	pSILAC	18668040
MIRT019994	hsa-miR-375	Microarray	20215506
MIRT024000	hsa-miR-1-3p	Proteomics	18668040
MIRT028637	hsa-miR-30a-5p	Proteomics	18668040
MIRT001448	hsa-miR-16-5p	Proteomics;Other	18668040
MIRT731965	hsa-miR-497-5p	Luciferase reporter assay, qRT-PCR, Western blot	27531900
MIRT731965	hsa-miR-497-5p	Luciferase reporter assay, qRT-PCR, Western blot	27531900
MIRT1082200	hsa-miR-103a	CLIP-seq
MIRT1082201	hsa-miR-107	CLIP-seq
MIRT1082202	hsa-miR-15a	CLIP-seq
MIRT1082203	hsa-miR-15b	CLIP-seq
MIRT1082204	hsa-miR-16	CLIP-seq
MIRT1082205	hsa-miR-195	CLIP-seq
MIRT1082206	hsa-miR-3135b	CLIP-seq
MIRT1082207	hsa-miR-3174	CLIP-seq
MIRT1082208	hsa-miR-338-3p	CLIP-seq
MIRT1082209	hsa-miR-3689d	CLIP-seq
MIRT1082210	hsa-miR-424	CLIP-seq
MIRT1082211	hsa-miR-4487	CLIP-seq
MIRT1082212	hsa-miR-4524	CLIP-seq
MIRT1082213	hsa-miR-4530	CLIP-seq
MIRT1082214	hsa-miR-4693-3p	CLIP-seq
MIRT1082215	hsa-miR-4786-3p	CLIP-seq
MIRT1082216	hsa-miR-497	CLIP-seq
MIRT1082217	hsa-miR-503	CLIP-seq
MIRT1082218	hsa-miR-545	CLIP-seq
MIRT1082219	hsa-miR-646	CLIP-seq
MIRT1082220	hsa-miR-766	CLIP-seq
MIRT1082221	hsa-miR-921	CLIP-seq
MIRT2020478	hsa-miR-1224-3p	CLIP-seq
MIRT2020479	hsa-miR-125a-3p	CLIP-seq
MIRT2020480	hsa-miR-1260	CLIP-seq
MIRT2020481	hsa-miR-1260b	CLIP-seq
MIRT2020482	hsa-miR-1280	CLIP-seq
MIRT2020483	hsa-miR-188-3p	CLIP-seq
MIRT2020484	hsa-miR-1912	CLIP-seq
MIRT2020485	hsa-miR-3130-5p	CLIP-seq
MIRT2020486	hsa-miR-3156-3p	CLIP-seq
MIRT2020487	hsa-miR-3677-3p	CLIP-seq
MIRT2020488	hsa-miR-3934	CLIP-seq
MIRT2020489	hsa-miR-4277	CLIP-seq
MIRT2020490	hsa-miR-4293	CLIP-seq
MIRT2020491	hsa-miR-4326	CLIP-seq
MIRT2020492	hsa-miR-4482	CLIP-seq
MIRT2020493	hsa-miR-4691-5p	CLIP-seq
MIRT2020494	hsa-miR-562	CLIP-seq
MIRT2020495	hsa-miR-596	CLIP-seq
MIRT2020496	hsa-miR-764	CLIP-seq
MIRT1082200	hsa-miR-103a	CLIP-seq
MIRT1082201	hsa-miR-107	CLIP-seq
MIRT1082202	hsa-miR-15a	CLIP-seq
MIRT1082203	hsa-miR-15b	CLIP-seq
MIRT1082204	hsa-miR-16	CLIP-seq
MIRT1082205	hsa-miR-195	CLIP-seq
MIRT1082206	hsa-miR-3135b	CLIP-seq
MIRT1082207	hsa-miR-3174	CLIP-seq
MIRT2252201	hsa-miR-3659	CLIP-seq
MIRT1082209	hsa-miR-3689d	CLIP-seq
MIRT1082210	hsa-miR-424	CLIP-seq
MIRT1082211	hsa-miR-4487	CLIP-seq
MIRT1082212	hsa-miR-4524	CLIP-seq
MIRT1082214	hsa-miR-4693-3p	CLIP-seq
MIRT1082216	hsa-miR-497	CLIP-seq
MIRT1082217	hsa-miR-503	CLIP-seq
MIRT1082219	hsa-miR-646	CLIP-seq
MIRT1082221	hsa-miR-921	CLIP-seq
MIRT2389671	hsa-miR-2467-3p	CLIP-seq
MIRT2389672	hsa-miR-3678-3p	CLIP-seq
MIRT2389673	hsa-miR-4447	CLIP-seq
MIRT2389674	hsa-miR-4472	CLIP-seq
MIRT2389675	hsa-miR-4481	CLIP-seq
MIRT2389676	hsa-miR-4745-5p	CLIP-seq
MIRT2389677	hsa-miR-591	CLIP-seq
MIRT2389678	hsa-miR-759	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
REST	Repression	16209944

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002376	Process	Immune system process	IEA
GO:0005267	Function	Potassium channel activity	TAS
GO:0005515	Function	Protein binding	IPI	12198491, 18796614, 27092946, 32296183
GO:0005516	Function	Calmodulin binding	IBA	21873635
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IDA	26148990
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Ion transport	IBA	21873635
GO:0006813	Process	Potassium ion transport	TAS	9380751
GO:0006816	Process	Calcium ion transport	IDA	18796614
GO:0006884	Process	Cell volume homeostasis	IEA
GO:0006952	Process	Defense response	TAS	9407042
GO:0008076	Component	Voltage-gated potassium channel complex	IC	18796614
GO:0015269	Function	Calcium-activated potassium channel activity	IDA	18796614, 26148990
GO:0016286	Function	Small conductance calcium-activated potassium channel activity	IEA
GO:0019903	Function	Protein phosphatase binding	IPI	18796614
GO:0022894	Function	Intermediate conductance calcium-activated potassium channel activity	IBA	21873635
GO:0030322	Process	Stabilization of membrane potential	IDA	18796614
GO:0031982	Component	Vesicle	IDA	25468996
GO:0043005	Component	Neuron projection	IBA	21873635
GO:0043025	Component	Neuronal cell body	IBA	21873635
GO:0045332	Process	Phospholipid translocation	IEA
GO:0046541	Process	Saliva secretion	IEA
GO:0050714	Process	Positive regulation of protein secretion	IEA
GO:0050862	Process	Positive regulation of T cell receptor signaling pathway	IDA	18796614
GO:0071805	Process	Potassium ion transmembrane transport	IBA	21873635

Other IDs

• MIM: 602754
• HGNC: 6293
• e!Ensembl: ENSG00000104783

Protein

• UniProt ID: O15554
• Protein name: Intermediate conductance calcium-activated potassium channel protein 4 (SKCa 4) (SKCa4) (hSK4) (Gardos channel) (IKCa1) (hIK1) (KCa3.1) (Putative Gardos channel) (hKCa4)
• Protein function: Intermediate 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 calc
• PDB: 6CNM, 6CNN, 6CNO, 6D42
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03530	SK_channel	11 → 124	Calcium-activated SK potassium channel	Family
  PF07885	Ion_trans_2	211 → 291	Ion channel	Family
  PF02888	CaMBD	304 → 375	Calmodulin binding domain	Family

• Sequence:

  MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFL
  VKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPA
  PVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYR
  SIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDT
  LWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHN
  FMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRK
  LREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLP
  EPSQQSK

• Sequence length: 427

Pathways

KEGG:

Insulin secretion
GnRH secretion
Salivary secretion
Protein digestion and absorption

Reactome:

Ca2+ activated K+ channels

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia, Hemolytic	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Breast carcinoma	Breast Carcinoma	rs80359671, rs11540652, rs28934575, rs28897672, rs137886232, rs193922376, rs80357783, rs80359306, rs80359405, rs80359507, rs80359598, rs80358429, rs397507683, rs397515636, rs80359451, rs397507859, rs80359709, rs80359742, rs80359205, rs80357627, rs80357004, rs80357571, rs80357767, rs80357653, rs80358086, rs80357608, rs28897696, rs41293465, rs146650273, rs63751017, rs63750617, rs63750726, rs63750199, rs63749848, rs398122618, rs398122653, rs397509211, rs80357791, rs121912666, rs587778541, rs121908698, rs536907995, rs587781302, rs140342925, rs587781506, rs587782652, rs587782849, rs587783057, rs10520699, rs11852999, rs139770721, rs374950566, rs786202800, rs863224451, rs377153250, rs747727055, rs876658804, rs780001540, rs760815829, rs878854926, rs775248597, rs886040658, rs886040192, rs786203523, rs886040319, rs397508006, rs587782011, rs1060502772, rs1555461727, rs1553333072, rs1114167702, rs1257401983, rs886040950, rs1060502759, rs774684620, rs142947311, rs1555580883, rs748513310, rs376170600, rs863224499, rs1593909229, rs748453607, rs1294578913, rs1574737047, rs1593909960, rs2081922847, rs2082559544, rs2053694038	29059683
Dehydrated hereditary stomatocytosis	DEHYDRATED HEREDITARY STOMATOCYTOSIS 2, Dehydrated hereditary stomatocytosis	rs774455945, rs1057519076, rs1057519077	26148990, 26178367, 26198474
Hyperbilirubinemia	Hyperbilirubinemia	rs34993780, rs587784535, rs797046090, rs797046091

Unknown
Disease name	Disease term	dbSNP ID	References
Abetalipoproteinemia	Abetalipoproteinemia
Xerocytosis	Xerocytosis		26148990, 26198474