KCNC2
potassium voltage-gated channel subfamily C member 2, the group of Potassium voltage-gated channels
Basic information
Region (hg38): 12:75040077-75209839
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy 103 (Strong), mode of inheritance: AD
- developmental and epileptic encephalopathy 103 (Strong), mode of inheritance: AD
- genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Developmental and epileptic encephalopathy 103 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 31972370; 32392612; 34448338; 35314505 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (47 variants)
- not_provided (43 variants)
- Developmental_and_epileptic_encephalopathy_103 (20 variants)
- KCNC2-related_disorder (6 variants)
- not_specified (5 variants)
- Developmental_and_epileptic_encephalopathy,_9 (1 variants)
- Developmental_and_epileptic_encephalopathy (1 variants)
- Neurodevelopmental_delay (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNC2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000139137.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 10 | 86 | 107 | |||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 8 | 10 | 91 | 6 | 2 |
Highest pathogenic variant AF is 0.0000012396935
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KCNC2 | protein_coding | protein_coding | ENST00000549446 | 4 | 169792 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.189 | 0.810 | 125738 | 0 | 10 | 125748 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.98 | 204 | 364 | 0.561 | 0.0000186 | 4095 |
| Missense in Polyphen | 36 | 156.63 | 0.22984 | 1837 | ||
| Synonymous | -2.01 | 189 | 157 | 1.20 | 0.00000880 | 1354 |
| Loss of Function | 3.07 | 5 | 19.7 | 0.254 | 0.00000105 | 240 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000309 | 0.0000309 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000530 | 0.0000527 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system. Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly. Forms tetrameric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:15709110). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties may be modulated either by the association with ancillary subunits, such as KCNE1, KCNE2 or KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG- mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in retinal ganglion cells, thalamocortical and suprachiasmatic nucleus (SCN) neurons and in hippocampal and neocortical interneurons (PubMed:15709110). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation-dependent manner. Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike-evoked calcium influx and GABA neurotransmitter release. Required for long-range synchronization of gamma oscillations over distance in the neocortex. Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (By similarity). {ECO:0000250|UniProtKB:P22462, ECO:0000250|UniProtKB:Q14B80, ECO:0000269|PubMed:15709110, ECO:0000305|PubMed:10414303, ECO:0000305|PubMed:11506885}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving KCNC2 has been found in a mother and her two children with varying degrees of neurodevelopmental delay and cerebellar ataxia. One child also exhibits episodes of unresponsiveness suggestive of absence seizures and facial dysmorphism. Deletion at 12q21.1 deletes exons 3-5 of KCNC2. {ECO:0000269|PubMed:23475819}.;
- Pathway
- Neuronal System;Voltage gated Potassium channels;Potassium Channels
(Consensus)
Recessive Scores
- pRec
- 0.0978
Intolerance Scores
- loftool
- 0.0257
- rvis_EVS
- -0.82
- rvis_percentile_EVS
- 11.68
Haploinsufficiency Scores
- pHI
- 0.285
- hipred
- Y
- hipred_score
- 0.586
- ghis
- 0.641
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.920
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kcnc2
- Phenotype
- limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype;
Gene ontology
- Biological process
- response to light intensity;response to organic cyclic compound;response to amine;globus pallidus development;response to magnesium ion;nitric oxide-cGMP-mediated signaling pathway;response to ethanol;regulation of insulin secretion;protein homooligomerization;protein heterooligomerization;cellular response to ammonium ion;cellular response to nitric oxide;potassium ion transmembrane transport;cellular response to toxic substance;regulation of presynaptic membrane potential;positive regulation of voltage-gated potassium channel activity;response to nerve growth factor
- Cellular component
- plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;membrane;integral component of membrane;basolateral plasma membrane;apical plasma membrane;cell junction;axon;dendrite;axolemma;vesicle;dendrite membrane;neuronal cell body membrane;presynaptic membrane;neuronal cell body;terminal bouton;perikaryon;synapse;postsynaptic membrane
- Molecular function
- voltage-gated potassium channel activity;delayed rectifier potassium channel activity;ion channel binding;voltage-gated ion channel activity involved in regulation of presynaptic membrane potential