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KCTD7
potassium channel tetramerization domain containing 7
KCTD7 is located on the long (q) arm of chromosome 7, at band 7q11.21. Arm ratio per GRCh38 - banding schematic.
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Overview
KCTD7 (potassium channel tetramerization domain containing 7) is located on chromosome 7 and encodes a 289-amino-acid protein thought to participate in neuronal function and survival. Although the precise molecular role of KCTD7 remains under investigation, evidence suggests the protein contributes to cellular quality control processes within the brain.
Pathogenic variants in KCTD7 follow an autosomal recessive inheritance pattern, meaning affected individuals carry alterations in both gene copies. Loss of functional KCTD7 protein is associated with a progressive neurological disorder that typically emerges in early childhood, characterised by seizures, cognitive decline, and motor impairment.
What the gene does
The KCTD7 protein is believed to participate in cellular pathways that maintain neuronal health, although its exact biochemical function has not been fully elucidated. Research suggests the protein may interact with components involved in protein degradation and cellular recycling, processes essential for removing damaged or misfolded proteins from neurons.
Evidence indicates KCTD7 may function within systems that regulate cellular responses to stress and coordinate protein turnover. Disruption of these quality-control mechanisms can lead to the accumulation of abnormal cellular material, particularly affecting neurons that have high metabolic demands. The protein's role appears most critical during brain development and in maintaining long-term neuronal function, which may explain why loss of KCTD7 activity manifests primarily as a neurological phenotype.
Given the gene's involvement in neuronal maintenance, researchers continue to investigate how KCTD7 integrates with broader cellular pathways that safeguard brain tissue from degenerative processes.
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Chromosome location
KCTD7 is located at chromosomal position 7q11.21 on the long arm of chromosome 7. This genomic region contains several genes involved in diverse cellular functions. The gene spans multiple exons that are transcribed and processed to generate the mature messenger RNA template for the KCTD7 protein.
Protein structure
The KCTD7 protein contains a BTB domain spanning amino acids 51 to 149, a structural element found in many proteins that mediate protein-protein interactions and participate in forming multi-subunit complexes. The BTB domain typically enables the assembly of functional protein units and may facilitate KCTD7's interactions with other cellular components.
The N-terminal region of the protein, encompassing amino acids 1 to 35, is predicted to be disordered, lacking a fixed three-dimensional structure. Disordered regions often serve regulatory roles or provide flexibility that allows proteins to interact with multiple binding partners. The combination of a structured BTB domain and flexible disordered region suggests KCTD7 functions as part of larger protein assemblies within the cell.
Key variants
Pathogenic variants in KCTD7 disrupt the protein's normal function, leading to loss of its cellular activity. Most disease-causing changes are predicted to result in absent or severely truncated protein products. Because KCTD7-related conditions follow autosomal recessive inheritance, affected individuals typically carry pathogenic variants on both gene copies, while carriers with one altered copy generally remain asymptomatic.
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.295C>T | p.Arg99Ter | Pathogenic | ★★☆☆ | Progressive myoclonic epilepsy type 3 |
c.339_340del | p.Asp115fs | Pathogenic | ★★☆☆ | Progressive myoclonic epilepsy type 3 |
c.550C>T | p.Arg184Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.631C>T | p.Arg211Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.827A>G | p.Tyr276Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Progressive myoclonic epilepsy type 3 |
g.(?_66068499)_(66098288_?)del | - | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy type 3 |
g.(?_66103220)_(66104219_?)del | - | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy type 3 |
c.338C>G | p.Ser113Ter | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy type 3 |
c.367C>T | p.Arg123Ter | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy type 3 |
c.514G>T | p.Glu172Ter | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy type 3 |
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
Biallelic pathogenic variants in KCTD7 cause a rare form of progressive myoclonic epilepsy, a neurological condition characterised by myoclonus (sudden muscle jerks), seizures that worsen over time, and progressive neurological deterioration. The condition typically presents in early childhood with developmental delay followed by regression of previously acquired skills.
Affected individuals experience a range of neurological symptoms including ataxia (impaired coordination), cognitive decline, and vision loss. The progressive nature of the disorder reflects ongoing neuronal dysfunction and degeneration in the absence of functional KCTD7 protein. This condition is classified among the neuronal ceroid lipofuscinoses, a group of inherited disorders affecting the nervous system.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic KCTD7 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
KCTD7 appears on several NHS Genomic Medicine Service gene panels with green classification, indicating strong evidence supporting its clinical validity. The gene is included in the DDG2P panel, the Early Onset or Syndromic Epilepsy panel (R59), the Intellectual Disability panel (R29), and the Neuronal Ceroid Lipofuscinosis panel (R231). These panel memberships reflect the gene's established role in early-onset neurological conditions and inform testing pathways within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does it mean to be a carrier of a KCTD7 variant?
Carriers have one altered KCTD7 gene copy and one working copy, which is typically sufficient for normal protein function. Carriers generally do not experience symptoms but can pass the variant to their children.
How is KCTD7-related epilepsy inherited?
The condition follows autosomal recessive inheritance, meaning a child must inherit pathogenic variants from both parents to be affected. When both parents are carriers, each pregnancy has a 25% chance of resulting in an affected child.
Is genetic testing for KCTD7 available through the NHS?
Testing may be available through NHS clinical genetics services for individuals with symptoms consistent with progressive myoclonic epilepsy or related neurological conditions. Referral typically requires assessment by a specialist.