KCNK4

Chr 11AD

potassium two pore domain channel subfamily K member 4

Also known as: FHEIG, K2p4.1, TRAAK, TRAAK1

NCBI Gene: 50801 ENSG00000182450 UniProt: Q9NYG8 OMIM: 605720

The protein forms homodimeric outwardly rectifying potassium channels that are regulated by polyunsaturated fatty acids, temperature, and mechanical membrane deformation, with primary expression in neural tissues where it may regulate noxious input thresholds in dorsal root ganglia neurons. Gain-of-function mutations cause an autosomal dominant syndrome characterized by facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth. The altered channel function likely disrupts normal neuronal excitability and potassium homeostasis in affected tissues.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the TWIK-related arachidonic acid-stimulated two pore potassium channel subfamily. The encoded protein homodimerizes and functions as an outwardly rectifying channel. This channel is regulated by polyunsaturated fatty acids, temperature and mechanical deformation of the lipid membrane. This protein is expressed primarily in neural tissues and may be involved in regulating the noxious input threshold in dorsal root ganglia neurons. Alternate splicing results in multiple transcript variants. Naturally occurring read-through transcripts also exist between this gene and the downstream testis expressed 40 (TEX40) gene, as represented in GeneID: 106780802. [provided by RefSeq, Nov 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndromeMIM #618381

Clinical highlights

Gene-disease validity (ClinGen)

facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome · ADModerateconsider for supplementary testing

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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.83

LOEUF

GOF*

Mechanism· G2P

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GeneReview available — KCNK4