GeneBe

KCND3

protein-coding

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

Gene summary

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]

Previous symbols:
  • SCA22
  • SCA19

MANE transcript

NM_001378969.1

Inheritance

AD

ClinVar variants

P:36U:330B:301

Top phenotype

Brugada syndrome 9

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr1:111,770,662-111,989,668

External References & Databases

Ensembl (ENSG00000171385)NCBI Gene (3752)OMIM (605411)HGNC:6239GenCCUniProt (Q9UK17)AlphaFoldClinVar (KCND3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~219.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spinocerebellar ataxia type 19/22STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011819

Submitter: Ambry Genetics

spinocerebellar ataxia type 19/22STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011819

Submitter: PanelApp Australia

Brugada syndrome 1NO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0011001

Submitter: ClinGen

Brugada syndrome 9LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014621

Submitter: Genomics England PanelApp

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

Brugada syndromeNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: G2P

spinocerebellar ataxia type 19/22STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011819

Submitter: Genomics England PanelApp

spinocerebellar ataxia type 19/22STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011819

Submitter: Labcorp Genetics (formerly Invitae)

spinocerebellar ataxia type 19/22SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011819

Submitter: Orphanet

Clinical Genomic Database (CGD)

Brugada syndrome 9AD

Manifestation: Cardiovascular; Neurologic

Intervention: Cardiovascular

Rationale: Individuals have been described as manifesting with arrhythmias and sudden cardiac death, and early diagnosis may allow management (such as with ICD placement)

Refs: 21349352; 22457051; 23280837; 23280838Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCND3 variants in ClinVar

16 Conditions Cataloged
Cardiovascular phenotypeTotal: 424
Spinocerebellar ataxia type 19/22Total: 360
not providedTotal: 201
not specifiedTotal: 67
Brugada syndrome 9Total: 26
KCND3-related disorderTotal: 18
Variant of unknown significanceTotal: 2
Neurodevelopmental delayTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378969.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
270
clinvar
4
clinvar
 278
missense
9
clinvar
26
clinvar
319
clinvar
26
clinvar
1
clinvar
 381
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
5
clinvar
 6
splice donor/acceptor (+/-2bp)
0
Total9273302965667

Highest pathogenic variant AF is 0.000013010653

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001378969.1RefSeqNP_001365898.17MANE Select
ENST00000302127.5EnsemblENSP00000306923.47MANE Select
NM_001378970.1RefSeqNP_001365899.16Standard
NM_004980.5RefSeqNP_004971.27Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Antiarrhythmic Pathway, Pharmacodynamics
  • Disopyramide Action Pathway
  • Procainamide (Antiarrhythmic) Action Pathway
  • Phenytoin (Antiarrhythmic) Action Pathway
  • Fosphenytoin (Antiarrhythmic) Action Pathway

Biological Process

  • potassium ion transport
  • regulation of ion transmembrane transport
  • protein homooligomerization
  • potassium ion transmembrane transport
  • membrane repolarization

Molecular Function

  • voltage-gated potassium channel activity
  • A-type (transient outward) potassium channel activity
  • protein binding
  • ion channel binding
  • metal ion binding

Cellular Component

  • plasma membrane
  • voltage-gated potassium channel complex
  • integral component of membrane
  • dendrite
  • sarcolemma

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000315987
Coding exons
7
Length
218494
Individuals with no LoFs
125740
Homozygous LoFs
0
Heterozygous LoFs
6
Defined
125746
p
0.0000239
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.852094350.4800.00003224293
Missense (PolyPhen)743.2520.16184360
Synonymous0.5501821920.9490.00001561343
Loss of Function4.01222.60.08860.00000109251

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits. {ECO:0000269|PubMed:10200233, ECO:0000269|PubMed:9843794}.;
Disease
DISEASE: Spinocerebellar ataxia 19 (SCA19) [MIM:607346]: A form of spinocerebellar ataxia, 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. SCA19 is a relatively mild, cerebellar ataxic syndrome with cognitive impairment, pyramidal tract involvement, tremor and peripheral neuropathy, and mild atrophy of the cerebellar hemispheres and vermis. {ECO:0000269|PubMed:23280837, ECO:0000269|PubMed:23280838, ECO:0000269|PubMed:28895081}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brugada syndrome 9 (BRGDA9) [MIM:616399]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:21349352, ECO:0000269|PubMed:22457051}. Note=The gene represented in this entry may be involved in disease pathogenesis.;

Recessive Scores

pRec
0.194

Intolerance Scores

LoFtool
0.0288
RVIS EVS
-0.8
RVIS percentile EVS
12.24

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.370

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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