KCNN3

Chr 1AD

potassium calcium-activated channel subfamily N member 3

Also known as: KCa2.3, SK3, SKCA3, ZLS3, hSK3

NCBI Gene: 3782 ENSG00000143603 UniProt: Q9UGI6 OMIM: 602983

The protein forms a small conductance calcium-activated potassium channel that regulates neuronal excitability by mediating afterhyperpolarization following action potentials. Mutations cause Zimmermann-Laband syndrome 3, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI=0.97, LOEUF=0.32), indicating strong intolerance to disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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 mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Zimmermann-Laband syndrome 3MIM #618658

Clinical highlights

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

GOF*

Mechanism· G2P

Some data sources returned errors (1)