KCNC3

potassium voltage-gated channel subfamily C member 3, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 19:50311936-50333515

Previous symbols: [ "SCA13" ]

Links

ENSG00000131398 ∙ NCBI:3748 ∙ OMIM:176264 ∙ HGNC:6235 ∙ Uniprot:Q14003 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 13 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 13 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 13 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 13 (Moderate), mode of inheritance: AD
• spinocerebellar ataxia type 13 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 13	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	16501573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNC3 gene.

• not provided (250 variants)
• Inborn genetic diseases (46 variants)
• not specified (30 variants)
• Spinocerebellar ataxia type 13 (30 variants)
• Tip-toe gait (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNC3 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			2	80	8	90
missense	2	2	125	10	5	144
nonsense		1	3			4
start loss			1			1
frameshift	1		5			6
inframe indel			8	1		9
splice donor/acceptor (+/-2bp)			1			1
splice region			1	4		5
non coding			1	17	6	24
Total	3	3	146	108	19

Highest pathogenic variant AF is 0.0000132

Variants in KCNC3

This is a list of pathogenic ClinVar variants found in the KCNC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-50314777-TCCCCACC-T		not specified	Uncertain significance (Mar 15, 2024)
19-50314910-G-T			Likely benign (Apr 01, 2023)
19-50320232-AG-A			Likely benign (Jan 19, 2022)
19-50320275-C-T		Spinocerebellar ataxia type 13	Uncertain significance (Nov 18, 2021)
19-50320276-G-A			Likely benign (Mar 01, 2020)
19-50320305-C-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
19-50320324-G-A			Benign (Jul 01, 2022)
19-50320324-G-C			Likely benign (Dec 31, 2019)
19-50320351-T-G		not specified	Uncertain significance (Apr 04, 2014)
19-50320357-T-G			Likely benign (Nov 01, 2023)
19-50320374-G-T			Likely benign (May 13, 2021)
19-50320375-A-G			Benign (May 12, 2021)
19-50320576-T-A			Likely benign (Apr 12, 2023)
19-50320577-AG-A			Benign (Mar 06, 2023)
19-50320579-G-A		Spinocerebellar ataxia type 13	Benign/Likely benign (Jan 19, 2024)
19-50320579-G-C			Benign (Nov 24, 2023)
19-50320579-G-T			Benign (Mar 26, 2023)
19-50320583-G-A			Likely benign (Apr 02, 2022)
19-50320585-C-A			Likely benign (Oct 17, 2022)
19-50320598-C-T			Uncertain significance (Apr 11, 2022)
19-50320607-C-A			Uncertain significance (Aug 27, 2019)
19-50320620-G-A		Spinocerebellar ataxia type 13	Uncertain significance (Apr 13, 2021)
19-50320624-A-G		not specified	Likely benign (Feb 01, 2021)
19-50320625-T-C			Uncertain significance (Dec 30, 2023)
19-50320626-A-G		Inborn genetic diseases	Uncertain significance (Jul 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNC3	protein_coding	protein_coding	ENST00000477616	4	21579

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.206	0.792	125688	0	17	125705	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.04	224	394	0.569	0.0000254	4831
Missense in Polyphen		73	186	0.39248		1937
Synonymous	-0.276	188	183	1.03	0.0000130	1686
Loss of Function	2.72	4	15.6	0.257	8.44e-7	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000715	0.0000704
Middle Eastern	0.000109	0.000109
South Asian	0.0000984	0.0000980
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. The channel displays rapid activation and inactivation kinetics (PubMed:10712820, PubMed:26997484, PubMed:22289912, PubMed:23734863, PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:25756792). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells. Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis (By similarity). Required for normal motor function (PubMed:23734863, PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:25756792). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484). {ECO:0000250|UniProtKB:Q63959, ECO:0000269|PubMed:10712820, ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606, ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912, ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25756792, ECO:0000269|PubMed:26997484}.
• Disease: DISEASE: Spinocerebellar ataxia 13 (SCA13) [MIM:605259]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA13 is an autosomal dominant cerebellar ataxia (ADCA) characterized by slow progression and variable age at onset, ranging from childhood to late adulthood. Mental retardation can be present in some patients. {ECO:0000269|PubMed:16501573, ECO:0000269|PubMed:19953606, ECO:0000269|PubMed:21479265, ECO:0000269|PubMed:22289912, ECO:0000269|PubMed:23734863, ECO:0000269|PubMed:25152487, ECO:0000269|PubMed:25756792}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: VEGFA-VEGFR2 Signaling Pathway;Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.178

Haploinsufficiency Scores

• pHI: 0.342
• hipred: Y
• hipred_score: 0.674
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnc3
• 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); 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: regulation of ion transmembrane transport;protein homooligomerization;protein tetramerization;potassium ion transmembrane transport
• Cellular component: cytoskeleton;plasma membrane;cell cortex;voltage-gated potassium channel complex;integral component of membrane;cell junction;axon;dendrite membrane;dendritic spine membrane;neuronal cell body membrane;presynaptic membrane;neuronal cell body;perikaryon
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity