KCNJ4

Chr 22

potassium inwardly rectifying channel subfamily J member 4

Also known as: HIR, HIRK2, HRK1, IRK-3, IRK3, Kir2.3

NCBI Gene: 3761 ENSG00000168135 UniProt: P48050

The protein is an inwardly rectifying potassium channel that preferentially allows potassium flow into cells rather than out, playing a key role in neuronal and muscle cell excitability. This gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.29), suggesting that mutations likely cause severe developmental phenotypes, though specific associated diseases have not yet been definitively established in the literature. The high constraint scores indicate that pathogenic variants in this gene would be expected to cause significant clinical consequences.

ResearchSummary from RefSeq, UniProt

Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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