KCNN2

Chr 5

potassium calcium-activated channel subfamily N member 2

Also known as: DYT34, KCa2.2, NEDMAB, SK2, SKCA2, SKCa 2, hSK2

NCBI Gene: 3781 ENSG00000080709 UniProt: Q9H2S1

This gene encodes a small conductance calcium-activated potassium channel that regulates neuronal excitability by mediating calcium-dependent potassium efflux and contributing to the afterhyperpolarization that follows action potentials. Mutations cause autosomal dominant dystonia 34 (myoclonic type) and neurodevelopmental disorder with variable movement or behavioral abnormalities. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.27), indicating intolerance to protein-disrupting mutations.

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. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDystonia 34, myoclonic

UniProtNeurodevelopmental disorder with or without variable movement or behavioral abnormalities

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.27

LOEUF· LoF intol.

LOF*

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429