KCNN4

Chr 19q13.31

potassium calcium-activated channel subfamily N member 4

Aliases:: KCa3.1, hSK4, hKCa4, hIKCa1, IK
MANE:: ENST00000648319.1

OMIM: 602754 ↗NCBI: 3783 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

KCNN4 · O15554

v62025-08-01

Predicted Aligned Error matrix for KCNN4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

84.2/ 100

Confident

427 residues

Confidence breakdown

Very high(≥ 90)51%
Confident(70–90)36%
Low(50–70)7%
Very low(< 50)7%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Rare anaemia
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

dehydrated hereditary stomatocytosis
0.72
hereditary disease
0.41
cystic fibrosis
0.39
breast carcinoma
0.37
dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema
0.35
breast cancer
0.26
luminal A breast carcinoma
0.25
sickle cell disease
0.19
reading
0.15
Alzheimer disease
0.13

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Intermediate conductance calcium-activated potassium channel protein 4

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 calcium allowing its opening (PubMed:10026195, PubMed:10961988, PubMed:11425865, PubMed:15831468, PubMed:17157250, PubMed:18796614, PubMed:26148990, PubMed:9326665, PubMed:9380751, PubMed:9407042). The current is characterized by a voltage-independent activation, an intracellular calcium concentration increase-dependent activation and a single-channel conductance of about 25 picosiemens (PubMed:9326665, PubMed:9380751, PubMed:9407042). Also presents an inwardly rectifying current, thus reducing its already small outward conductance of potassium ions, which is particularly the case when the membrane potential displays positive values, above + 20 mV (PubMed:9326665, PubMed:9380751, PubMed:9407042). Controls calcium influx during vascular contractility by being responsible of membrane hyperpolarization induced by vasoactive factors in proliferative vascular smooth muscle cell types (By similarity). Following calcium influx, the consecutive activation of KCNN4 channel leads to a hyperpolarization of the cell membrane potential and hence an increase of the electrical driving force for further calcium influx promoting sustained calcium entry in response to stimulation with chemotactic peptides (PubMed:26418693). Required for maximal calcium influx and proliferation during the reactivation of naive T-cells (PubMed:17157250, PubMed:18796614). Plays a role in the late stages of EGF-induced macropinocytosis through activation by PI(3)P (PubMed:24591580)