KCNQ1

Chr 11ADAR

potassium voltage-gated channel subfamily Q member 1

Also known as: ATFB1, ATFB3, JLNS1, KCNA8, KCNA9, KVLQT1, Kv1.9, Kv7.1

NCBI Gene: 3784 ENSG00000053918 UniProt: P51787 OMIM: 607542

This gene encodes a voltage-gated potassium channel subunit that is essential for cardiac repolarization and also functions in the inner ear, stomach, and colon. Mutations cause long QT syndrome type 1 (Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, short QT syndrome type 2, and familial atrial fibrillation, with inheritance patterns that are autosomal dominant for isolated cardiac phenotypes and autosomal recessive for Jervell and Lange-Nielsen syndrome which includes both cardiac arrhythmias and congenital deafness. The gene is extremely intolerant to loss-of-function variants (pLI near 0, LOEUF 0.81), reflecting its critical role in cardiac and auditory function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Long QT syndrome 1, acquired, susceptibility to}MIM #192500

Atrial fibrillation, familial, 3MIM #607554

Jervell and Lange-Nielsen syndromeMIM #220400

Long QT syndrome 1MIM #192500

Short QT syndrome 2MIM #609621

UniProtType 2 diabetes mellitus

Clinical highlights

Gene-disease validity (ClinGen)

Jervell and Lange-Nielsen syndrome · ARDefinitivesufficient evidence for diagnostic panels4 gene-disease associations curated in total

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

174

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

Multiple*

Mechanism· G2P

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