KCNC1

potassium voltage-gated channel subfamily C member 1, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 11:17734773-17856804

Links

ENSG00000129159 ∙ NCBI:3746 ∙ OMIM:176258 ∙ HGNC:6233 ∙ Uniprot:P48547 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive myoclonic epilepsy type 7 (Definitive), mode of inheritance: AD
• progressive myoclonic epilepsy type 7 (Definitive), mode of inheritance: AD
• progressive myoclonic epilepsy type 7 (Supportive), mode of inheritance: AD
• progressive myoclonic epilepsy type 7 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• progressive myoclonus epilepsy (Definitive), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progressive myoclonic 7	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	25401298

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNC1 gene.

• Progressive myoclonic epilepsy type 7 (332 variants)
• not provided (82 variants)
• Inborn genetic diseases (40 variants)
• not specified (3 variants)
• KCNC1-related condition (2 variants)
• Abnormal cerebral morphology (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNC1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	142	7	156
missense		10	164	6		180
nonsense		1	2			3
start loss						0
frameshift		2	4			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region				1	1	2
non coding			1	14	6	21
Total	0	13	180	162	13

Variants in KCNC1

This is a list of pathogenic ClinVar variants found in the KCNC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-17735870-C-A			Benign (Jul 15, 2018)
11-17736013-G-A		Progressive myoclonic epilepsy type 7	Uncertain significance (Jun 22, 2019)
11-17736017-C-T			Uncertain significance (Jun 01, 2016)
11-17736018-G-C		Progressive myoclonic epilepsy type 7	Uncertain significance (Mar 03, 2022)
11-17736024-G-T			Likely pathogenic (Sep 01, 2021)
11-17736032-C-T		Progressive myoclonic epilepsy type 7	Likely benign (Nov 23, 2022)
11-17736038-C-A		Progressive myoclonic epilepsy type 7	Likely benign (Apr 17, 2021)
11-17736053-G-A		Progressive myoclonic epilepsy type 7	Likely benign (Nov 05, 2017)
11-17736062-G-A		Progressive myoclonic epilepsy type 7	Likely benign (Oct 18, 2022)
11-17736070-G-A		Progressive myoclonic epilepsy type 7	Uncertain significance (Jun 04, 2022)
11-17736073-C-G		Progressive myoclonic epilepsy type 7	Uncertain significance (May 29, 2022)
11-17736074-G-A		not specified • Progressive myoclonic epilepsy type 7 • Inborn genetic diseases	Benign (Feb 01, 2024)
11-17736076-C-T		Progressive myoclonic epilepsy type 7	Uncertain significance (Oct 10, 2023)
11-17736080-G-C		Progressive myoclonic epilepsy type 7	Likely benign (Nov 27, 2021)
11-17736086-G-A		Progressive myoclonic epilepsy type 7	Likely benign (Jan 26, 2023)
11-17736092-C-A		Progressive myoclonic epilepsy type 7	Uncertain significance (Sep 28, 2019)
11-17736093-G-A		Progressive myoclonic epilepsy type 7	Uncertain significance (Oct 25, 2021)
11-17736093-G-C			Uncertain significance (Sep 28, 2019)
11-17736098-G-A		Progressive myoclonic epilepsy type 7	Likely benign (Oct 07, 2023)
11-17736104-C-A		Progressive myoclonic epilepsy type 7 • Inborn genetic diseases	Likely benign (Dec 27, 2023)
11-17736104-C-T		Progressive myoclonic epilepsy type 7	Likely benign (May 30, 2023)
11-17736107-C-G		Progressive myoclonic epilepsy type 7	Likely benign (Dec 30, 2023)
11-17736108-TG-T		Progressive myoclonic epilepsy type 7	Likely pathogenic (Oct 08, 2018)
11-17736116-G-A		Progressive myoclonic epilepsy type 7 • Inborn genetic diseases	Likely benign (Jan 10, 2024)
11-17736122-C-G		Progressive myoclonic epilepsy type 7	Likely benign (May 07, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNC1	protein_coding	protein_coding	ENST00000265969	4	48244

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.0104	124714	0	3	124717	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.52	139	390	0.356	0.0000267	3802
Missense in Polyphen		35	190.68	0.18356		1879
Synonymous	1.28	159	181	0.879	0.0000145	1201
Loss of Function	3.73	1	18.1	0.0551	8.67e-7	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000985	0.0000985
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient (PubMed:25401298). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well. Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons. {ECO:0000250|UniProtKB:P25122, ECO:0000269|PubMed:25401298}.
• Disease: DISEASE: Epilepsy, progressive myoclonic 7 (EPM7) [MIM:616187]: A neurologic disorder characterized by progressive myoclonic epilepsy, manifesting in the first or second decades of life. Cognitive function may decline in some patients. Myoclonus is a brief, involuntary twitching of a muscle or a group of muscles. {ECO:0000269|PubMed:25401298}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.0102
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.62

Haploinsufficiency Scores

• pHI: 0.122
• hipred: Y
• hipred_score: 0.825
• ghis: 0.666

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.732

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kcnc1
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: potassium ion transport;response to toxic substance;response to light intensity;response to auditory stimulus;response to amine;cerebellum development;globus pallidus development;cellular response to drug;response to potassium ion;protein homooligomerization;protein tetramerization;response to fibroblast growth factor;potassium ion transmembrane transport;regulation of presynaptic membrane potential;positive regulation of voltage-gated potassium channel activity;response to nerve growth factor
• Cellular component: plasma membrane;voltage-gated potassium channel complex;cell surface;integral component of membrane;axon;axolemma;dendrite membrane;neuronal cell body membrane;neuronal cell body;calyx of Held;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;kinesin binding;ion channel binding;voltage-gated ion channel activity involved in regulation of presynaptic membrane potential