KCNH1

Chr 1AD

potassium voltage-gated channel subfamily H member 1

Also known as: EAG, EAG1, K(V)10.1, Kv10.1, TMBTS, ZLS1, h-eag, hEAG

NCBI Gene: 3756 ENSG00000143473 UniProt: O95259 OMIM: 603305

The protein forms voltage-gated potassium channels that regulate neuronal excitability and is highly expressed in brain and muscle. Gain-of-function mutations cause Temple-Baraitser syndrome and Zimmermann-Laband syndrome 1, both inherited in an autosomal dominant pattern. The pathogenic mechanism involves altered potassium channel function that disrupts normal neuronal signaling.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Temple-Baraitser syndromeMIM #611816

Zimmermann-Laband syndrome 1MIM #135500

Clinical highlights

Gene-disease validity (ClinGen)

KCNH1 associated disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the established mechanism, 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

0.39

LOEUF

GOF

Mechanism· annotated

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GeneReview available — KCNH1