On this page
KCNQ5
potassium voltage-gated channel subfamily Q member 5
KCNQ5 encodes a voltage-gated potassium channel essential for controlling electrical signalling in the brain and nervous system. The KCNQ5 gene provides instructions for making a protein that forms part of a voltage-gated potassium channel, which regulates the flow of potassium ions across nerve cell membranes.
KCNQ5 is located on the long (q) arm of chromosome 6, at band 6q13. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 6 in the library →Overview
KCNQ5 belongs to the KCNQ family of voltage-gated potassium channels, which play fundamental roles in controlling electrical excitability in nerve and muscle cells. The protein encoded by this gene forms channels that allow potassium ions to flow out of cells in response to changes in membrane voltage, helping to reset neurons after they fire and preventing over-excitation. This regulatory function is particularly important in the brain, where precise control of neuronal firing patterns is essential for normal cognitive function and seizure prevention.
Variants that impair KCNQ5 channel function can lead to neurological manifestations, reflecting the protein's critical role in maintaining balanced electrical activity in the nervous system. The gene is recognised in UK clinical genetics panels for epilepsy and intellectual disability, highlighting its clinical relevance in neurodevelopmental and neurological conditions.
What the gene does
The KCNQ5 protein forms voltage-gated potassium channels that regulate the flow of potassium ions across cell membranes in response to changes in electrical potential. These channels function as tetramers, meaning four protein subunits assemble together to create a functional pore through which potassium ions can pass. KCNQ5 can form channels either by combining four identical KCNQ5 subunits or by partnering with other KCNQ family members such as KCNQ3, creating heterotetrameric channels with distinct functional properties.
The primary cellular function of KCNQ5 channels is to generate M-current, a slowly activating potassium current that helps stabilise the resting membrane potential of neurons and limits repetitive firing. By allowing potassium ions to exit the cell, KCNQ5 channels counteract depolarising influences and help prevent excessive neuronal excitability. This moderating effect is crucial in brain regions involved in learning, memory and seizure control. The channels are modulated by calmodulin and other regulatory proteins, which fine-tune their activity in response to cellular conditions and signalling pathways.
Video: Genetics 101
Chromosome location
KCNQ5 is located on the long arm of chromosome 6 at position 6q13. This chromosomal region contains multiple genes involved in neurological function and development. The genomic structure of KCNQ5 spans a substantial region, with the gene organised into multiple exons that encode the 932 amino acid protein through alternative splicing and regulatory mechanisms.
Protein structure
The KCNQ5 protein is 932 amino acids in length and contains several functionally important regions. The protein includes two regions for interaction with calmodulin (a calcium-binding regulatory protein), located at amino acids 370-378 and 521-528, which allow calcium-dependent regulation of channel activity. The structure also contains three disordered regions at amino acids 404-465, 655-678, and 876-919. These disordered segments are flexible portions of the protein that may facilitate interactions with regulatory molecules or undergo conformational changes during channel gating. Like other KCNQ family members, KCNQ5 contains six transmembrane domains that form the channel pore and voltage-sensing apparatus, though detailed structural mapping of all functional domains continues to be refined through ongoing research.
Key variants
Pathogenic variants in KCNQ5 typically affect the channel's ability to properly regulate potassium ion flow, either by impairing voltage sensing, disrupting pore formation, or interfering with regulatory interactions. Loss-of-function variants that reduce channel activity can lead to neuronal hyperexcitability, whilst some variants may produce gain-of-function effects with different clinical consequences. The inheritance pattern is autosomal dominant (monoallelic mechanism, meaning variants in one gene copy are sufficient to cause disease), so a single altered copy of the gene in each cell is sufficient to cause related conditions, though the severity and specific features can vary even within families.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1039G>A | p.Gly347Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Intellectual disability, autosomal dominant 46 |
c.1105C>A | p.Pro369Thr | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.532C>T | p.Arg178Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Intellectual disability, autosomal dominant 46 |
c.739C>T | p.Arg247Ter | Pathogenic | ★★☆☆ | Intellectual disability, autosomal dominant 46 |
g.(?_73331918)_(73905137_?)del | - | Pathogenic | ★☆☆☆ | not provided |
c.1040G>C | p.Gly347Ala | Pathogenic | ★☆☆☆ | Intellectual disability, autosomal dominant 46 |
c.1105C>T | p.Pro369Ser | Pathogenic | ★☆☆☆ | not provided |
c.1106C>A | p.Pro369Gln | Pathogenic | ★☆☆☆ | Intellectual disability, autosomal dominant 46 |
c.1286G>T | p.Ser429Ile | Pathogenic | ★☆☆☆ | Intellectual disability, autosomal dominant 46 |
c.253del | p.Ala85fs | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in KCNQ5 are associated with neurological conditions affecting brain development and function. The gene is recognised on UK clinical genetics panels for early-onset or syndromic epilepsy and intellectual disability, reflecting its role in maintaining proper neuronal excitability. Individuals with pathogenic KCNQ5 variants may experience seizures, developmental delays, learning difficulties, or a combination of neurological features. The phenotype can range from relatively mild learning difficulties to more significant developmental and epileptic encephalopathy (severe epilepsy with developmental impairment), depending on the specific variant and individual factors. The specific manifestations and severity can vary depending on the nature and location of the genetic variant and how it affects channel function.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic KCNQ5 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
In the UK National Health Service Genomic Medicine Service, KCNQ5 is included on several clinical gene panels. It appears as a green gene on the DDG2P panel (monoallelic mechanism), the Early Onset or Syndromic Epilepsy panel (R59), and the Intellectual Disability panel (R29). Green classification indicates strong evidence linking variants in this gene to the relevant conditions, supporting its use in clinical diagnostic testing for patients presenting with seizures, developmental delay, or intellectual disability.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What conditions are associated with KCNQ5 variants?
Pathogenic variants in KCNQ5 are associated with neurological conditions including epilepsy and intellectual disability. The gene is recognised on UK clinical genetics panels for early-onset or syndromic epilepsy and developmental disorders affecting cognition and learning.
How is KCNQ5 inherited?
KCNQ5-related conditions follow an autosomal dominant inheritance pattern. This means a variant in just one copy of the gene can be sufficient to cause the associated condition, and an affected parent has a 50% chance of passing the variant to each child.
What is the function of KCNQ5 in the brain?
KCNQ5 forms voltage-gated potassium channels that help regulate neuronal excitability by generating M-current. This current stabilises nerve cell activity and prevents excessive firing, which is essential for normal brain function and seizure prevention.