Functional Annotation of KCTD7 (BTB/POZ Domain-Containing Protein KCTD7) in Human

Gene Identity and Key Characteristics

KCTD7 (Potassium Channel Tetramerization Domain-containing protein 7) is a human protein encoded by the KCTD7 gene (UniProt Q96MP8). Despite its name, KCTD7 is not an ion channel itself, but was named for a conserved N-terminal domain homologous to the T1 tetramerization domain of Kv potassium channels (pubmed.ncbi.nlm.nih.gov). This N-terminal region is a BTB/POZ domain – a ~120-amino-acid Broad-Complex/Tramtrack/Bric-à-brac motif – which mediates protein-protein interactions and homo-oligomerization (pmc.ncbi.nlm.nih.gov). The human genome encodes 26 KCTD family members sharing this structural motif (pmc.ncbi.nlm.nih.gov). KCTD7 is one of these BTB-domain proteins, originally of unknown function but implicated in a rare pediatric epilepsy syndrome (pmc.ncbi.nlm.nih.gov). It was first identified in 2007 when KCTD7 mutations were found to cause progressive myoclonic epilepsy type 3 (EPM3), a severe early-onset epilepsy with neurodegeneration (pmc.ncbi.nlm.nih.gov). Pathogenic variants in KCTD7 also lead to neuronal ceroid lipofuscinosis 14 (CLN14) – a form of Batten disease – and have been reported in opsoclonus-myoclonus ataxia syndrome, underscoring the gene’s clinical significance (pmc.ncbi.nlm.nih.gov). In summary, KCTD7 is a BTB-domain adapter protein whose loss of function causes infantile-onset epilepsy and neurodegenerative disease, suggesting it plays an essential role in neuronal physiology.

Expression and Subcellular Localization

KCTD7 is predominantly a neuronal protein, expressed broadly in the central nervous system. Initial studies in mice showed high expression in the cerebellar Purkinje cells, hippocampus, and cortical neurons (www.ncbi.nlm.nih.gov). Human transcriptome data indicate KCTD7 is expressed in many tissues but is enriched in the brain and retina, fitting with its neuron-specific functions (www.proteinatlas.org) (www.proteinatlas.org). In fact, KCTD7 mRNA is classified as “tissue-enhanced” in retina and brain, clustering with genes involved in neuronal signaling (www.proteinatlas.org) (www.proteinatlas.org). Within cells, KCTD7 is localized to the cytosol. Confocal microscopy reveals KCTD7 has a diffuse cytosolic distribution, and it co-localizes with its binding partners in the cytoplasm (pmc.ncbi.nlm.nih.gov). Biochemical fractionation confirms that both KCTD7 and its known substrates are highly enriched in the cytosolic fraction, with little presence in membrane or nuclear compartments (pmc.ncbi.nlm.nih.gov). (Notably, one study reported a minor membrane association for a mutant substrate, as discussed below, but wild-type KCTD7 itself is mainly intracellular cytosolic (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).) This subcellular localization aligns with KCTD7’s role as a cytosolic regulatory protein, rather than a membrane-spanning receptor or channel. In summary, KCTD7 is expressed postnatally in neurons of the CNS (and to a lesser extent in other tissues) and functions primarily in the cytosolic compartment of the cell (www.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Molecular Function: Cullin-3 E3 Ubiquitin Ligase Adaptor

Current Understanding: KCTD7’s primary molecular function is as an adaptor protein for a Cullin-3 (CUL3) E3 ubiquitin ligase complex. Like many BTB-domain proteins, KCTD7 can bind CUL3 and recruit specific substrate proteins for ubiquitination (pmc.ncbi.nlm.nih.gov). Early evidence of this came from Azizieh et al. (2011), who showed that KCTD7 physically interacts with CUL3 in co-immunoprecipitation assays (pubmed.ncbi.nlm.nih.gov). This suggested KCTD7 might function analogously to other BTB-containing ubiquitin ligase adaptors (e.g. KLHL family proteins), even before its substrates were known. Indeed, the BTB/POZ domain in KCTD7 is required for CUL3 binding (pmc.ncbi.nlm.nih.gov), and disease-causing mutations in KCTD7 disrupt the KCTD7–CUL3 interaction (pmc.ncbi.nlm.nih.gov). Once bound to CUL3, KCTD7 forms a Cullin-3 RING ligase (CRL3) complex together with the Rbx1 RING-finger protein (which recruits a ubiquitin-conjugating enzyme) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In this complex, KCTD7 serves as the substrate-recognition subunit (the “adapter”) that confers target specificity (pmc.ncbi.nlm.nih.gov). Until recently, the identity of KCTD7’s target substrates was unclear, and the protein’s function was “uncharacterized” in molecular terms (pmc.ncbi.nlm.nih.gov). However, breakthrough studies in 2022–2023 have identified two key substrate pathways of KCTD7’s CRL3 complex: one involving calpain proteases and another involving a lysosomal trafficking protein CLN5.

• Regulation of Calpain Proteases: In 2023, Sharma et al. discovered that KCTD7 targets the ubiquitous calcium-dependent proteases calpain-1 (CAPN1) and calpain-2 (CAPN2) for atypical, non-degradative ubiquitination (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Normally, calpains are cysteine proteases that cleave various substrates and are tightly regulated in cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The KCTD7–CUL3 complex was found to bind directly to calpain-1 and -2 (via the calpain domain III) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) and attach multi-ubiquitin chains on specific lysine residues of the calpains (lysine-398 on calpain-1, and lysines-280/674 on calpain-2) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These chains were “atypical” ubiquitin linkages (mainly K6-, K27-, K29-, and K63-linked chains rather than the canonical K48 proteasomal tag) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Importantly, adding these ubiquitin chains did not lead to calpain degradation – consistent with no change in calpain levels upon KCTD7 manipulation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) – but instead suppressed calpain activity (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Mechanistically, ubiquitination of calpain reduced its enzymatic activity and altered its localization: mutant calpain-1 that cannot be ubiquitinated (K398R) showed abnormally increased binding to its stabilizing subunit (CAPNS1) and mislocalized more to the plasma membrane, resulting in hyperactivation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By ubiquitinating calpains, KCTD7 keeps these proteases largely cytosolic and in a restrained state (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This negative regulation of calpain is a novel function – it effectively tethers and inactivates calpains via ubiquitin signals rather than destroying them. Loss of KCTD7 leads to unchecked calpain activity (see Biological Processes below), which has dire consequences for neurons (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This recent finding “unveils a novel mechanism” for controlling calpains and positions KCTD7 as a critical regulator of protease signaling (pmc.ncbi.nlm.nih.gov).

• Regulation of Lysosomal Protein (CLN5): In 2022, Wang et al. reported another KCTD7 target that illuminates the lysosomal storage aspect of KCTD7-deficient disease (pmc.ncbi.nlm.nih.gov). They found that the CRL3–KCTD7 complex targets the lysosomal protein CLN5 for ubiquitin-mediated degradation* (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). *CLN5 is a glycoprotein required for lysosomal enzyme trafficking, and mutations in CLN5 cause a form of Batten disease. In KCTD7’s normal function, it binds and ubiquitinates CLN5, marking it for proteasomal turnover (pmc.ncbi.nlm.nih.gov). In cells lacking functional KCTD7, CLN5 accumulates to abnormally high levels, and this excess CLN5 disrupts lysosomal enzyme trafficking (pmc.ncbi.nlm.nih.gov). Specifically, the accumulated CLN5 was shown to interfere with the interactions of CLN6/CLN8 (ER proteins) with lysosomal hydrolases in the endoplasmic reticulum, thereby blocking ER-to-Golgi transport of multiple lysosomal enzymes (pmc.ncbi.nlm.nih.gov). The result is a broad lysosomal dysfunction with reduced delivery of enzymes to lysosomes and consequent buildup of undegraded substrates (manifesting as ceroid lipofuscin storage in neurons) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This work revealed “previously unrecognized roles of KCTD7-mediated CLN5 proteolysis in lysosomal homeostasis” (pmc.ncbi.nlm.nih.gov). In essence, KCTD7 normally acts to degrade CLN5 at the proper time, preventing CLN5 from reaching excessive levels that would perturb the lysosomal system (pmc.ncbi.nlm.nih.gov). The 2022 study also noted that disease-causing mutations in KCTD7 often disrupt the KCTD7–CUL3 interaction or the KCTD7–CLN5 binding, thus impairing ubiquitination of CLN5 and leading to its pathological accumulation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Together with the calpain findings, this identifies KCTD7 as a multi-functional adaptor: it can assemble distinct CRL3 complexes to modulate both protease activity (calpains) and protein turnover (lysosomal enzymes) depending on the substrate. These molecular functions explain how KCTD7 loss derails cellular homeostasis on multiple fronts.

Biological Processes and Pathways Involving KCTD7

Through the above molecular interactions, KCTD7 is involved in several critical biological processes:

• Regulation of Neuronal Excitability: A hallmark of KCTD7’s function is its impact on neuronal resting membrane potential and excitability. Loss-of-function mutations in KCTD7 lead to neuronal hyperexcitability and seizures, whereas KCTD7 overexpression causes hypo-excitability. In patch-clamp studies on cultured neurons, introducing KCTD7 was found to hyperpolarize the cell’s resting membrane potential and reduce firing frequency (pubmed.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). Conversely, neurons lacking KCTD7 (or from KCTD7-deficient mice) show a depolarized resting potential and increased propensity for spontaneous firing and seizures (www.ncbi.nlm.nih.gov). This effect was demonstrated by Van Bogaert et al. and Azizieh et al.: patient-derived KCTD7 nonsense mutations resulted in depolarized neuronal membranes, while wild-type KCTD7 transfection drove a more negative resting potential (www.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). The mechanism underlying this electrophysiological effect appears to be indirect via KCTD7’s control of calpain. Calpain hyperactivity can cleave neuronal ion channels and synaptic proteins, potentially leading to altered ion currents. For example, excessive calpain activity is known to cleave the K-Cl cotransporter KCC2 and other regulators of inhibitory signaling, which can make GABAergic currents depolarizing (pmc.ncbi.nlm.nih.gov). Although the exact substrates in KCTD7-deficient neurons remain under investigation, the current model is that KCTD7 restrains calpains to maintain ion channel and receptor integrity, thereby stabilizing the resting membrane potential. In KCTD7’s absence, calpains likely aberrantly cleave key ion channel subunits or scaffold proteins, resulting in reduced potassium conductance and neuronal depolarization (pubmed.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). Supporting this, KCTD7 was originally described as a “regulator of potassium conductance in neurons” based on its hyperpolarizing effect (www.jle.com). Thus, KCTD7 is intimately involved in neuronal excitability pathways – not by acting as a channel itself, but by safeguarding the components (channels, transporters, etc.) that determine neuronal resting potential and firing thresholds.

• Ubiquitin-Proteasome and Protein Quality Control Pathways: As an adaptor for a ubiquitin ligase, KCTD7 is part of the ubiquitin-proteasome system (UPS). It guides the CRL3 E3 ligase to specific targets, thereby influencing protein stability and signaling. One relevant pathway is the antigen processing and MHC class I presentation pathway, where ubiquitination plays a key role in generating peptides – indeed, pathway databases list KCTD7 among proteins in ubiquitination modules of antigen presentation (www.genecards.org). More directly, KCTD7-mediated ubiquitination of CLN5 ties it into the lysosome–autophagy pathway: by regulating lysosomal enzyme trafficking, KCTD7 affects cellular degradative capacity and proteostasis (pmc.ncbi.nlm.nih.gov). In KCTD7-deficient cells, lysosomal catabolic function is impaired (due to misrouting of enzymes), linking KCTD7 to lysosomal storage disease mechanisms (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This places KCTD7 at the crossroads of UPS and lysosomal degradation pathways – two major proteolytic systems in cells. Additionally, KCTD7’s control of calpains represents involvement in a non-lysosomal protease pathway: calpains are calcium-activated proteases that modulate cytoskeletal dynamics, cell death, synaptic plasticity, and other processes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By restraining calpain activity, KCTD7 indirectly influences these downstream pathways. For instance, calpain hyperactivation can trigger apoptotic cascades; in KCTD7 knockout neurons, unchecked calpain led to excessive cleavage of α-spectrin (a cytoskeletal protein) and activation of caspase-3, a hallmark of apoptosis (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Therefore, KCTD7 participates in cell survival pathways, preventing aberrant protease activation that would otherwise damage the cytoskeleton and activate cell death programs. In summary, KCTD7 links to multiple biochemical pathways: it is a component of the Cullin–RING ubiquitin ligase network, it upholds lysosomal function by regulating enzyme trafficking, and it modulates calcium-dependent signaling through calpain control. These combined actions maintain neuronal health by balancing protein turnover and proteolysis.

• Neurodevelopment and Neurovascular Interactions: Emerging evidence suggests KCTD7 also plays a role in neurodevelopmental processes, likely as a downstream consequence of its core functions. A 2019 study examined KCTD7 in mouse retinal development – an accessible CNS model – and found that Kctd7 knockout mice have defects in retinal neuron populations and blood vessel patterning (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, Kctd7⁻/⁻ mice showed ~30% increases in abnormal branching of retinal vasculature in deep layers, along with significantly altered vessel density (pmc.ncbi.nlm.nih.gov). These vascular defects were traced to neuronal causes: KCTD7 is expressed in inner retinal neurons (but not in vessels), and loss of KCTD7 led to an excess of certain interneurons (bipolar cells) during development, which in turn dysregulated angiogenic cues (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By postnatal day 8, Kctd7⁻/⁻ retinas had ~21% more bipolar cells than normal, correlating with delayed and disorganized vessel layer formation (pmc.ncbi.nlm.nih.gov). Functional consequences were seen in the electroretinogram: Kctd7⁻/⁻ mice had ~30–40% reduced retinal responses (a- and b-wave amplitudes), indicating impaired retinal circuit function (pmc.ncbi.nlm.nih.gov). This study highlights that neuronal KCTD7 influences neurovascular development, potentially through regulating proteostasis in developing neurons that secrete angiogenic factors. While the precise molecular mechanism wasn’t fully resolved, the authors suggest it may involve KCTD7-regulated neurovascular signaling – an example of how KCTD7’s cellular role (protease regulation) can have broader tissue-level effects (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These findings align with the human phenotype: children with KCTD7 mutations often experience developmental regression and neurological decline, hinting that KCTD7 is required for normal neural network maturation. Thus, beyond its immediate biochemical pathways, KCTD7 contributes to higher-order biological processes like synaptic development and neuron–glia–vascular interactions necessary for healthy brain function (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Clinical Significance and Current Developments

Disease Association: Mutations in KCTD7 cause KCTD7-related Progressive Myoclonic Epilepsy (PME), also designated EPM3, which typically begins in infancy. A review of reported cases shows onset of neurological symptoms (myoclonic seizures often being the first sign) between about 5 months and 3 years of age (www.ncbi.nlm.nih.gov). Affected infants develop frequent, refractory seizures (myoclonic and generalized types) and progressive neurocognitive decline. Importantly, many patients also exhibit features of a lysosomal storage disorder: some have intracellular inclusions of lipofuscin in tissues, linking this condition to neuronal ceroid lipofuscinosis (now classified as CLN14 in the NCL disease spectrum) (pmc.ncbi.nlm.nih.gov). Pathogenic variants in KCTD7 are usually biallelic loss-of-function (e.g. nonsense, frameshift, or missense disrupting the BTB domain). For example, the first family described had a homozygous nonsense mutation (p.R184) (www.jle.com), and subsequent studies identified various missense mutations that abolish either CUL3 binding or substrate interaction (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By 2012, at least a half-dozen distinct KCTD7 mutations were reported across unrelated PME families worldwide (www.jle.com) (www.jle.com), and more have been discovered since (including compound heterozygous cases in diverse ethnic backgrounds (www.jle.com)). Genetic testing for KCTD7 mutations is now part of the diagnostic workup for early-onset progressive myoclonic epilepsies (www.ncbi.nlm.nih.gov), and a 2025 review noted that KCTD7* mutations account for a small but significant subset of PME cases globally (www.ncbi.nlm.nih.gov).

Pathogenic Mechanism: The convergence of recent research has largely clarified how KCTD7 loss leads to disease. The two major pathogenic mechanisms are calpain hyperactivation and lysosomal dysfunction, as described above. In KCTD7-deficient neurons, calpain activity is abnormally high, resulting in excessive cleavage of neuronal substrates and synaptic proteins (pmc.ncbi.nlm.nih.gov). This likely causes synaptic deterioration, altered ion channel function, and activation of cell death pathways (caspase-3 mediated apoptosis), which together produce epilepsy and neurodegeneration (pmc.ncbi.nlm.nih.gov). At the same time, accumulation of CLN5 and mis-trafficking of lysosomal enzymes lead to lysosomal storage and impaired waste clearance in neurons (pmc.ncbi.nlm.nih.gov). This combination – excitotoxicity from protease overactivity and toxic buildup from lysosomal failure – explains the rapid neurodegeneration seen in patients. Notably, mouse models of KCTD7 deficiency closely mirror the human disease: Kctd7⁻/⁻ mice develop ataxia, motor impairment, and progressive neurodegeneration (for instance, they show significant Purkinje cell loss in the cerebellum accompanied by activated caspase-3 and gliosis) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These mice also exhibit spontaneous seizures and shortened lifespans, validating the causal role of KCTD7 loss in epilepsy. Importantly, when Kctd7-knockout mice were treated with a calpain inhibitor, their neurodegenerative phenotypes were largely rescued (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Sharma et al. (2023) administered the broad-spectrum calpain inhibitor E-64 to Kctd7⁻/⁻ mice starting at weaning, and over 5 weeks this treatment significantly prevented the usual decline: the Kctd7 knockout mice on E-64 showed preserved motor function and much less neuronal death compared to untreated knockouts (pmc.ncbi.nlm.nih.gov). This striking result demonstrates that calpain hyperactivation is a major driver of pathology in KCTD7-related disease, and that it can be ameliorated by therapeutically targeting calpains (pmc.ncbi.nlm.nih.gov). It also proves the principle that the molecular discoveries have direct translational potential.

Current and Future Applications: While there is currently no cure for KCTD7-PME/CLN14, these new insights suggest potential interventions. One avenue is the use of calpain inhibitors as a therapeutic strategy. Some calpain inhibitors (such as MDL-28170 and others) have shown neuroprotective effects in preclinical models of neurodegeneration (pmc.ncbi.nlm.nih.gov). In fact, selective calpain inhibitors are in early clinical trials for conditions like Alzheimer’s disease (pmc.ncbi.nlm.nih.gov), given calpain’s role in neurodegenerative pathways. For KCTD7-deficient patients, calpain inhibition could conceivably reduce neuronal damage and slow disease progression – a hypothesis supported by the mouse rescue experiments (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Another application is in diagnostics and counseling: recognizing that KCTD7 mutations cause a syndrome that overlaps epilepsy and Batten disease has led to broader genetic screening. Children presenting with unexplained early epilepsy and developmental regression are now often tested for KCTD7 among other genes (www.ncbi.nlm.nih.gov). Early diagnosis can inform supportive care (seizure management, physical therapy, low-vision interventions if applicable) and allow family planning via carrier testing (www.ncbi.nlm.nih.gov). From a research standpoint, KCTD7 is now a promising target to study neurodegeneration mechanisms. Its dual control of calpains and lysosomal function links two key pathological processes. Experts have noted that calpain hyperactivity contributes to common disorders such as type II diabetes, muscular dystrophy, and neurodegenerative diseases like Parkinson’s and Alzheimer’s (pmc.ncbi.nlm.nih.gov). Thus, understanding the KCTD7–calpain regulatory axis could yield insight into those diseases as well. The discovery of KCTD7’s role as a calpain “brake” is particularly significant – as one 2023 paper emphasized, these results reveal “a novel mechanism and potential target to restrain calpain activity in human disease” (pmc.ncbi.nlm.nih.gov). In a broader sense, KCTD7 exemplifies how a once-mysterious protein can be functionally annotated through modern techniques (tandem affinity purification, CRISPR knockouts, cryo-EM structures (pdbj.org)) to uncover its interactome and role. The cryo-EM structure of the KCTD7–CUL3 complex (solved in 2023) now provides a blueprint at atomic resolution for how KCTD7 assembles with CUL3 (pdbj.org). This structural knowledge could guide drug discovery – for instance, screening for small molecules that enhance or mimic KCTD7’s binding to calpain, effectively substituting its function in patients with loss-of-function mutations. In summary, current research is not only deepening our understanding of KCTD7’s function but is actively suggesting therapeutic angles, from repurposing calpain inhibitors to potentially stabilizing the mutant KCTD7–CUL3 complex, all of which offer hope for addressing the devastating disorder caused by KCTD7 mutations.

Expert Commentary

Authoritative sources highlight the importance of KCTD7 in maintaining neuronal homeostasis. A 2025 clinical review notes that KCTD7 is expressed widely in the CNS and that its loss leads to an “inherited defect of the neuron plasma membrane’s resting potential”, linking this to the observed seizures (www.ncbi.nlm.nih.gov). This underscores that KCTD7’s effect on excitability is a primary feature of the disease. In a 2022 Science Advances article, researchers remarked that their findings “reveal previously unrecognized roles of KCTD7-mediated [protein] proteolysis in lysosomal homeostasis” and that KCTD7 and its substrate CLN5 “function in a common neurodegenerative pathway.” (pmc.ncbi.nlm.nih.gov). This expert analysis places KCTD7 as a key node in the network of proteins that, when disrupted, lead to neurodegeneration. Likewise, the 2023 study by Sharma et al. concluded that “these results unveil a novel mechanism … to restrain calpain activity in human disease and shed light on the molecular pathogenesis of KCTD7-associated disease.” (pmc.ncbi.nlm.nih.gov). Leading epilepsy researchers (e.g. Minassian et al., 2016) have pointed out that KCTD7 firmly belongs in the PME gene catalog alongside ion-channel genes, even though KCTD7 itself is not an ion channel – an insight that only makes sense now that we know it regulates ion channel-modulating proteases (www.jle.com) (www.ncbi.nlm.nih.gov). In summary, experts consider KCTD7 a crucial regulator of neuronal stability, whose absence triggers a cascade of proteostatic and excitability disturbances. The recent elucidation of its molecular function has been hailed as an important step toward understanding and eventually treating the severe epilepsy and neurodegeneration seen in KCTD7 deficiency (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

In conclusion, KCTD7 is a BTB-domain adaptor protein that plays a vital role in neurons by assembling a Cullin-3 ubiquitin ligase complex to ubiquitinate specific targets. It protects neurons from hyperexcitability and degeneration by (1) dampening calpain protease activity through non-degradative ubiquitination, and (2) promoting lysosomal protein turnover (e.g. degrading CLN5) to ensure proper enzyme trafficking. Its loss leads to a combination of uncontrolled proteolysis and lysosomal dysfunction, explaining the progressive epilepsy and neuronal cell death in patients with KCTD7 mutations. Ongoing research (2022–2024) has not only clarified these functions with molecular precision but also opened avenues for therapeutic intervention, exemplifying how functional annotation of a previously enigmatic gene can directly inform clinical strategies. The story of KCTD7 – from an obscure “potassium channel tetramerization” protein to a key modulator of calpains and neuronal survival – highlights the power of modern genomics and proteomics in uncovering the critical roles of proteins that were once defined only by name and sequence. (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)

References: (Key references in chronological order)

• Van Bogaert et al. (2007), Annals of Neurology – Identified KCTD7 mutation in progressive myoclonic epilepsy (pmc.ncbi.nlm.nih.gov).
• Azizieh et al. (2011), Molecular Neurobiology – Demonstrated KCTD7’s hyperpolarizing effect on neurons and interaction with CUL3 (pubmed.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov).
• Staropoli et al. (2012), American Journal of Human Genetics – Linked KCTD7 mutation to ubiquitin-proteasome system and ceroid lipofuscinosis (www.jle.com).
• Liu et al. (2013), Cell & Bioscience – Reviewed KCTD protein family structure/function (pmc.ncbi.nlm.nih.gov).
• Alevy et al. (2019), Neurochemistry International – Kctd7 knockout mouse study showing retinal neurovascular defects (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
• Wang et al. (2022), Science Advances – Showed CRL3-KCTD7 targets CLN5 for degradation; explained lysosomal pathology (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
• Sharma et al. (2023), Cell Discovery – Identified calpains as substrates of KCTD7-Cullin3 complex; uncovered non-degradative ubiquitination mechanism (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
• GeneReviews (2025) – Comprehensive clinical synopsis of KCTD7-PME/CLN14, with updated molecular insights (www.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov).

Citations

1. AnnotationURLCitation(end_index=617, start_index=446, title='Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21710140/#:~:text=The%20potassium%20channel%20tetramerization%20domain,in%20the%20hippocampal%20and%20Purkinje')
2. AnnotationURLCitation(end_index=958, start_index=799, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=KCTD7%20has%20been%20shown%20to,ligases%20%28CRLs%29%20and%20function%20as')
3. AnnotationURLCitation(end_index=1165, start_index=1038, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=not%20well%20understood,But%20whether%20and')
4. AnnotationURLCitation(end_index=1435, start_index=1294, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=unknown%20function%20that%20is%20defective,30%20%2C%2032')
5. AnnotationURLCitation(end_index=1756, start_index=1615, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=unknown%20function%20that%20is%20defective,30%20%2C%2032')
6. AnnotationURLCitation(end_index=2128, start_index=1987, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=unknown%20function%20that%20is%20defective,30%20%2C%2032')
7. AnnotationURLCitation(end_index=2788, start_index=2589, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=KCTD7%20is%20expressed%20postnatally%20throughout,causes%20hyperpolarization%20and%20decreased%20excitation')
8. AnnotationURLCitation(end_index=3122, start_index=2947, title='Tissue expression of KCTD7 - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000243335-KCTD7/tissue#:~:text=HUMAN%20PROTEIN%20ATLAS%20INFORMATION,i%7D%20Pending%20normal%20tissue%20annotation')
9. AnnotationURLCitation(end_index=3273, start_index=3123, title='Tissue expression of KCTD7 - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000243335-KCTD7/tissue#:~:text=cluster%20%28RNA%29,i%7D%20Evidence%20at%20protein%20level')
10. AnnotationURLCitation(end_index=3581, start_index=3406, title='Tissue expression of KCTD7 - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000243335-KCTD7/tissue#:~:text=HUMAN%20PROTEIN%20ATLAS%20INFORMATION,i%7D%20Pending%20normal%20tissue%20annotation')
11. AnnotationURLCitation(end_index=3751, start_index=3582, title='Tissue expression of KCTD7 - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000243335-KCTD7/tissue#:~:text=Pending%20normal%20tissue%20annotation,based%20on%20tissue%20RNA%20expression')
12. AnnotationURLCitation(end_index=4074, start_index=3941, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=necessary%20and%20sufficient%20for%20calpain,S1g')
13. AnnotationURLCitation(end_index=4386, start_index=4256, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=KCTD7%20with%20either%20calpain%20subunits,38')
14. AnnotationURLCitation(end_index=4686, start_index=4551, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=match%20at%20L315%20calpain%201,K398R%20expression')
15. AnnotationURLCitation(end_index=4802, start_index=4687, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=calpain%201,K398R%20expression')
16. AnnotationURLCitation(end_index=5319, start_index=5120, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=KCTD7%20is%20expressed%20postnatally%20throughout,causes%20hyperpolarization%20and%20decreased%20excitation')
17. AnnotationURLCitation(end_index=5450, start_index=5320, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=KCTD7%20with%20either%20calpain%20subunits,38')
18. AnnotationURLCitation(end_index=5926, start_index=5767, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=KCTD7%20has%20been%20shown%20to,ligases%20%28CRLs%29%20and%20function%20as')
19. AnnotationURLCitation(end_index=6226, start_index=6072, title='Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21710140/#:~:text=of%20KCTD7%20in%20patients%20with,of%20the%20neuron%20plasma%20membrane%27s')
20. AnnotationURLCitation(end_index=6590, start_index=6463, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=that%20KCTD7%20interacts%20with%20Cullin,3')
21. AnnotationURLCitation(end_index=6799, start_index=6668, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Immunoprecipitation%20%28IP%29%20of%20Cullin,1')
22. AnnotationURLCitation(end_index=7117, start_index=6966, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=1c%20%29.%20Cullin,probably%20functions%20as%20an%20intramolecular')
23. AnnotationURLCitation(end_index=7245, start_index=7118, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Co,an%20adapter%20for%20calpain%20subunits')
24. AnnotationURLCitation(end_index=7521, start_index=7362, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=KCTD7%20has%20been%20shown%20to,ligases%20%28CRLs%29%20and%20function%20as')
25. AnnotationURLCitation(end_index=7803, start_index=7662, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=unknown%20function%20that%20is%20defective,30%20%2C%2032')
26. AnnotationURLCitation(end_index=8396, start_index=8255, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=protein%20of%20previously%20uncharacterized%20function,3')
27. AnnotationURLCitation(end_index=8562, start_index=8397, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=show%20that%20KCTD7%20works%20in,and%20resulted%20in%20calpain%20hyperactivation')
28. AnnotationURLCitation(end_index=8839, start_index=8672, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Calpains%20are%20a%20class%20of,function%20whose%20pathogenic%20mutations%20result')
29. AnnotationURLCitation(end_index=8998, start_index=8840, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Calpains%20are%20a%20unique%20class,to%20the%20involvement%20of%20calpain')
30. AnnotationURLCitation(end_index=9243, start_index=9099, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=interaction%20between%20KCTD7%20and%20calpain,Supplementary')
31. AnnotationURLCitation(end_index=9371, start_index=9244, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Co,an%20adapter%20for%20calpain%20subunits')
32. AnnotationURLCitation(end_index=9629, start_index=9510, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=non,mediated%20ubiquitination%20to')
33. AnnotationURLCitation(end_index=9762, start_index=9630, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=KCTD7%E2%80%93Cullin,2%20at%20K280%20and%20K674')
34. AnnotationURLCitation(end_index=10029, start_index=9910, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=non,mediated%20ubiquitination%20to')
35. AnnotationURLCitation(end_index=10195, start_index=10030, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=show%20that%20KCTD7%20works%20in,and%20resulted%20in%20calpain%20hyperactivation')
36. AnnotationURLCitation(end_index=10503, start_index=10350, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=To%20test%20whether%20calpains%20are,cells%20did%20not%20result%20in')
37. AnnotationURLCitation(end_index=10676, start_index=10504, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=We%20therefore%20sought%20to%20determine,without%20affecting%20their%20protein%20levels')
38. AnnotationURLCitation(end_index=10895, start_index=10723, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=We%20therefore%20sought%20to%20determine,without%20affecting%20their%20protein%20levels')
39. AnnotationURLCitation(end_index=11050, start_index=10896, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=i%29.%20Cleaved%20caspase,ubiquitin%20ligase%20controls%20calpain%201')
40. AnnotationURLCitation(end_index=11472, start_index=11357, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=calpain%201,K398R%20expression')
41. AnnotationURLCitation(end_index=11622, start_index=11473, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=activation.%20Ubiquitination,for%20calpain%201%20stability%20and')
42. AnnotationURLCitation(end_index=11837, start_index=11724, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=calpain%201,CAPNS1%20complex')
43. AnnotationURLCitation(end_index=11987, start_index=11838, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=activation.%20Ubiquitination,for%20calpain%201%20stability%20and')
44. AnnotationURLCitation(end_index=12406, start_index=12278, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=K27,associated%20disease.%20Finally%2C%20we')
45. AnnotationURLCitation(end_index=12561, start_index=12407, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=i%29.%20Cleaved%20caspase,ubiquitin%20ligase%20controls%20calpain%201')
46. AnnotationURLCitation(end_index=12878, start_index=12702, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=calpain%20hyperactivation%2C%20aberrant%20cleavage%20of,shed%20light%20on%20the%20molecular')
47. AnnotationURLCitation(end_index=13215, start_index=13053, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
48. AnnotationURLCitation(end_index=13496, start_index=13334, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
49. AnnotationURLCitation(end_index=13647, start_index=13497, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=a%20unique%20NCL%20subtype,demonstrate%20that%20KCTD7%20and%20CLN5')
50. AnnotationURLCitation(end_index=14022, start_index=13872, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=a%20unique%20NCL%20subtype,demonstrate%20that%20KCTD7%20and%20CLN5')
51. AnnotationURLCitation(end_index=14320, start_index=14170, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=a%20unique%20NCL%20subtype,demonstrate%20that%20KCTD7%20and%20CLN5')
52. AnnotationURLCitation(end_index=14708, start_index=14558, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=a%20unique%20NCL%20subtype,demonstrate%20that%20KCTD7%20and%20CLN5')
53. AnnotationURLCitation(end_index=15045, start_index=14906, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=Lysosomes%20are%20central%20organelles%20for,CLN5%20and')
54. AnnotationURLCitation(end_index=15208, start_index=15046, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
55. AnnotationURLCitation(end_index=15458, start_index=15321, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=enzymes,in%20a%20common%20neurodegenerative%20pathway')
56. AnnotationURLCitation(end_index=15781, start_index=15619, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
57. AnnotationURLCitation(end_index=16168, start_index=16006, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
58. AnnotationURLCitation(end_index=16324, start_index=16169, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=Mechanistically%2C%20the%20CRL3,demonstrate%20that%20KCTD7%20and%20CLN5')
59. AnnotationURLCitation(end_index=17435, start_index=17281, title='Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21710140/#:~:text=of%20KCTD7%20in%20patients%20with,of%20the%20neuron%20plasma%20membrane%27s')
60. AnnotationURLCitation(end_index=17577, start_index=17436, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Bogaert%20et%20al%202007,Azizieh%20et%20al%202011')
61. AnnotationURLCitation(end_index=17887, start_index=17746, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Bogaert%20et%20al%202007,Azizieh%20et%20al%202011')
62. AnnotationURLCitation(end_index=18323, start_index=18124, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=KCTD7%20is%20expressed%20postnatally%20throughout,causes%20hyperpolarization%20and%20decreased%20excitation')
63. AnnotationURLCitation(end_index=18465, start_index=18324, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Bogaert%20et%20al%202007,Azizieh%20et%20al%202011')
64. AnnotationURLCitation(end_index=19039, start_index=18887, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=cause%20human%20disease,calpains%2C%20however%2C%20do%20not%20exist')
65. AnnotationURLCitation(end_index=19624, start_index=19453, title='Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21710140/#:~:text=The%20potassium%20channel%20tetramerization%20domain,in%20the%20hippocampal%20and%20Purkinje')
66. AnnotationURLCitation(end_index=19766, start_index=19625, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Bogaert%20et%20al%202007,Azizieh%20et%20al%202011')
67. AnnotationURLCitation(end_index=20065, start_index=19905, title='JLE - Epileptic Disorders - KCTD7-related progressive myoclonus epilepsy', type='url_citation', url='https://www.jle.com/en/revues/epd/e-docs/kctd7_related_progressive_myoclonus_epilepsy_307897/article.phtml?tab=references#:~:text=,A%20compound')
68. AnnotationURLCitation(end_index=20930, start_index=20829, title='KCTD7 Gene - GeneCards | KCTD7 Protein | KCTD7 Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=KCTD7#:~:text=,KCTD7%20Gene')
69. AnnotationURLCitation(end_index=21301, start_index=21139, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
70. AnnotationURLCitation(end_index=21622, start_index=21460, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
71. AnnotationURLCitation(end_index=21778, start_index=21623, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=Mechanistically%2C%20the%20CRL3,demonstrate%20that%20KCTD7%20and%20CLN5')
72. AnnotationURLCitation(end_index=22304, start_index=22137, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Calpains%20are%20a%20class%20of,function%20whose%20pathogenic%20mutations%20result')
73. AnnotationURLCitation(end_index=22463, start_index=22305, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Calpains%20are%20a%20unique%20class,to%20the%20involvement%20of%20calpain')
74. AnnotationURLCitation(end_index=22918, start_index=22790, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=K27,associated%20disease.%20Finally%2C%20we')
75. AnnotationURLCitation(end_index=23073, start_index=22919, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=i%29.%20Cleaved%20caspase,ubiquitin%20ligase%20controls%20calpain%201')
76. AnnotationURLCitation(end_index=24161, start_index=24010, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=trilaminar%20vascular%20network,of%20the%20superficial%20and%20deep')
77. AnnotationURLCitation(end_index=24316, start_index=24162, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=Together%2C%20these%20data%20suggest%20that,related%20human%20diseases')
78. AnnotationURLCitation(end_index=24643, start_index=24474, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=a%20significant%20increase%20in%20vessel,deep%20layers%20was%20also%20correspondingly')
79. AnnotationURLCitation(end_index=25064, start_index=24904, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=vascular%20layers%20were%20delayed,and%20increased%20vessel%20branching%20in')
80. AnnotationURLCitation(end_index=25219, start_index=25065, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=Together%2C%20these%20data%20suggest%20that,related%20human%20diseases')
81. AnnotationURLCitation(end_index=25511, start_index=25364, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=development%20was%20altered,postnatal%20week%2C%20as%20by%20P12')
82. AnnotationURLCitation(end_index=25840, start_index=25698, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=match%20at%20L408%20conditions%2C%20resulting,s%2Fm%5E%7B2')
83. AnnotationURLCitation(end_index=26421, start_index=26267, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=Together%2C%20these%20data%20suggest%20that,related%20human%20diseases')
84. AnnotationURLCitation(end_index=26549, start_index=26422, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=not%20well%20understood,But%20whether%20and')
85. AnnotationURLCitation(end_index=27126, start_index=26972, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=Together%2C%20these%20data%20suggest%20that,related%20human%20diseases')
86. AnnotationURLCitation(end_index=27246, start_index=27127, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=match%20at%20L58%20Alevy%20et,These')
87. AnnotationURLCitation(end_index=27752, start_index=27624, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=,about%20one%20third%20of%20affected')
88. AnnotationURLCitation(end_index=28282, start_index=28141, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=unknown%20function%20that%20is%20defective,30%20%2C%2032')
89. AnnotationURLCitation(end_index=28663, start_index=28511, title='JLE - Epileptic Disorders - KCTD7-related progressive myoclonus epilepsy', type='url_citation', url='https://www.jle.com/en/revues/epd/e-docs/kctd7_related_progressive_myoclonus_epilepsy_307897/article.phtml?tab=references#:~:text=S,586')
90. AnnotationURLCitation(end_index=28915, start_index=28784, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Immunoprecipitation%20%28IP%29%20of%20Cullin,1')
91. AnnotationURLCitation(end_index=29066, start_index=28916, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=a%20unique%20NCL%20subtype,demonstrate%20that%20KCTD7%20and%20CLN5')
92. AnnotationURLCitation(end_index=29385, start_index=29180, title='JLE - Epileptic Disorders - KCTD7-related progressive myoclonus epilepsy', type='url_citation', url='https://www.jle.com/en/revues/epd/e-docs/kctd7_related_progressive_myoclonus_epilepsy_307897/article.phtml?tab=references#:~:text=opsoclonus,gene%20and%20progressive%20myoclonic%20epilepsy')
93. AnnotationURLCitation(end_index=29538, start_index=29386, title='JLE - Epileptic Disorders - KCTD7-related progressive myoclonus epilepsy', type='url_citation', url='https://www.jle.com/en/revues/epd/e-docs/kctd7_related_progressive_myoclonus_epilepsy_307897/article.phtml?tab=references#:~:text=,1398')
94. AnnotationURLCitation(end_index=29796, start_index=29645, title='JLE - Epileptic Disorders - KCTD7-related progressive myoclonus epilepsy', type='url_citation', url='https://www.jle.com/en/revues/epd/e-docs/kctd7_related_progressive_myoclonus_epilepsy_307897/article.phtml?tab=references#:~:text=,399')
95. AnnotationURLCitation(end_index=30067, start_index=29923, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Molecular%20genetic%20testing%20approaches%20can,see')
96. AnnotationURLCitation(end_index=30309, start_index=30181, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=,about%20one%20third%20of%20affected')
97. AnnotationURLCitation(end_index=30825, start_index=30697, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=K27,associated%20disease.%20Finally%2C%20we')
98. AnnotationURLCitation(end_index=31178, start_index=31024, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=i%29.%20Cleaved%20caspase,ubiquitin%20ligase%20controls%20calpain%201')
99. AnnotationURLCitation(end_index=31492, start_index=31330, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
100. AnnotationURLCitation(end_index=32077, start_index=31945, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=match%20at%20L440%20of%20Purkinje,compared%20to')
101. AnnotationURLCitation(end_index=32218, start_index=32078, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=of%20Purkinje%20cells%20associated%20with,compared%20to')
102. AnnotationURLCitation(end_index=32657, start_index=32481, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=calpain%20hyperactivation%2C%20aberrant%20cleavage%20of,shed%20light%20on%20the%20molecular')
103. AnnotationURLCitation(end_index=32790, start_index=32658, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=death%20associated%20with%20caspase,degradative')
104. AnnotationURLCitation(end_index=33257, start_index=33116, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Kctd7,epoxysuccinyl%20group%20%28active%20moiety%29%20of')
105. AnnotationURLCitation(end_index=33584, start_index=33452, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=death%20associated%20with%20caspase,degradative')
106. AnnotationURLCitation(end_index=34209, start_index=34039, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=pharmacological%20calpain%20inhibitors%20are%20being,23%2C24%2C88%2C89%7D.%20A%20more')
107. AnnotationURLCitation(end_index=34462, start_index=34318, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=match%20at%20L1301%20pharmacodynamics%20of,Google%20Scholar')
108. AnnotationURLCitation(end_index=34833, start_index=34692, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=Kctd7,epoxysuccinyl%20group%20%28active%20moiety%29%20of')
109. AnnotationURLCitation(end_index=34966, start_index=34834, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=death%20associated%20with%20caspase,degradative')
110. AnnotationURLCitation(end_index=35434, start_index=35290, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Molecular%20genetic%20testing%20approaches%20can,see')
111. AnnotationURLCitation(end_index=35746, start_index=35604, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=,allow%20reliable%20recurrence%20risk%20assessment')
112. AnnotationURLCitation(end_index=36281, start_index=36129, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=cause%20human%20disease,calpains%2C%20however%2C%20do%20not%20exist')
113. AnnotationURLCitation(end_index=36782, start_index=36611, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=prevented%20by%20pharmacological%20inhibition%20of,shed%20light%20on%20the%20molecular')
114. AnnotationURLCitation(end_index=37073, start_index=36976, title='8i79 - Cryo-EM structure of KCTD7 in complex with Cullin3 - Summary - Protein Data Bank Japan', type='url_citation', url='https://pdbj.org/mine/summary/8i79#:~:text=8i79%20,3%20%282%20entities%20in%20total')
115. AnnotationURLCitation(end_index=37354, start_index=37257, title='8i79 - Cryo-EM structure of KCTD7 in complex with Cullin3 - Summary - Protein Data Bank Japan', type='url_citation', url='https://pdbj.org/mine/summary/8i79#:~:text=8i79%20,3%20%282%20entities%20in%20total')
116. AnnotationURLCitation(end_index=38444, start_index=38245, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=KCTD7%20is%20expressed%20postnatally%20throughout,causes%20hyperpolarization%20and%20decreased%20excitation')
117. AnnotationURLCitation(end_index=38948, start_index=38811, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=enzymes,in%20a%20common%20neurodegenerative%20pathway')
118. AnnotationURLCitation(end_index=39474, start_index=39298, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=calpain%20hyperactivation%2C%20aberrant%20cleavage%20of,shed%20light%20on%20the%20molecular')
119. AnnotationURLCitation(end_index=39958, start_index=39778, title='JLE - Epileptic Disorders - KCTD7-related progressive myoclonus epilepsy', type='url_citation', url='https://www.jle.com/en/revues/epd/e-docs/kctd7_related_progressive_myoclonus_epilepsy_307897/article.phtml?tab=references#:~:text=Epilepsia.%202012%3B53%3A1387,208')
120. AnnotationURLCitation(end_index=40100, start_index=39959, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Bogaert%20et%20al%202007,Azizieh%20et%20al%202011')
121. AnnotationURLCitation(end_index=40638, start_index=40462, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=calpain%20hyperactivation%2C%20aberrant%20cleavage%20of,shed%20light%20on%20the%20molecular')
122. AnnotationURLCitation(end_index=40771, start_index=40639, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=death%20associated%20with%20caspase,degradative')
123. AnnotationURLCitation(end_index=42077, start_index=41936, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=unknown%20function%20that%20is%20defective,30%20%2C%2032')
124. AnnotationURLCitation(end_index=42249, start_index=42078, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=prevented%20by%20pharmacological%20inhibition%20of,shed%20light%20on%20the%20molecular')
125. AnnotationURLCitation(end_index=42566, start_index=42425, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=unknown%20function%20that%20is%20defective,30%20%2C%2032')
126. AnnotationURLCitation(end_index=42857, start_index=42703, title='Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21710140/#:~:text=of%20KCTD7%20in%20patients%20with,of%20the%20neuron%20plasma%20membrane%27s')
127. AnnotationURLCitation(end_index=42999, start_index=42858, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=Bogaert%20et%20al%202007,Azizieh%20et%20al%202011')
128. AnnotationURLCitation(end_index=43346, start_index=43148, title='JLE - Epileptic Disorders - KCTD7-related progressive myoclonus epilepsy', type='url_citation', url='https://www.jle.com/en/revues/epd/e-docs/kctd7_related_progressive_myoclonus_epilepsy_307897/article.phtml?tab=references#:~:text=Progressive%20Myoclonus%20Epilepsies%3A%20State,208')
129. AnnotationURLCitation(end_index=43568, start_index=43441, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=not%20well%20understood,But%20whether%20and')
130. AnnotationURLCitation(end_index=43844, start_index=43693, title='Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6702070/#:~:text=trilaminar%20vascular%20network,of%20the%20superficial%20and%20deep')
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132. AnnotationURLCitation(end_index=44301, start_index=44139, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=accumulation%20of%20ceroid%20in%20neurons,Golgi%20trafficking%20of%20lysosomal')
133. AnnotationURLCitation(end_index=44439, start_index=44302, title='KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9348797/#:~:text=enzymes,in%20a%20common%20neurodegenerative%20pathway')
134. AnnotationURLCitation(end_index=44738, start_index=44597, title='Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10038992/#:~:text=protein%20of%20previously%20uncharacterized%20function,3')
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136. AnnotationURLCitation(end_index=45203, start_index=45004, title='KCTD7-Related Progressive Myoclonic Epilepsy - GeneReviews® - NCBI Bookshelf', type='url_citation', url='https://www.ncbi.nlm.nih.gov/books/n/gene/kctd7-epilepsy/#:~:text=KCTD7%20is%20expressed%20postnatally%20throughout,causes%20hyperpolarization%20and%20decreased%20excitation')
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