Summary Statistics:
Gene Score: 2
Relevance to Autism
A de novo balanced translocation t(3;8)(q21;q24) with a breakpoint lying within intron 1 of the KCNQ3 gene was identified in a Danish boy diagnosed with childhood autism. Furthermore, the same KCNQ3 missense variant (c.1720C>T; p.P574S) was identified in three unrelated individuals with childhood autism and no history of convulsions; this variant resulted in significant reduction of potassium current amplitude when co-expressed with KV7.5 in Xenopus oocytes (Gilling et al., 2013).
Molecular Function
This gene encodes a protein that functions in the regulation of neuronal excitability. The encoded protein forms an M-channel by associating with the products of the related KCNQ2 or KCNQ5 genes, which both encode integral membrane proteins. M-channel currents are inhibited by M1 muscarinic acetylcholine receptors and are activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2).
References
Primary
Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders.
ASD
Positive Association
De novo mutations in epileptic encephalopathies.
Epilepsy
IS, LGS, DD, ID, ASD, ADHD
Positive Association
Family-based association analysis to finemap bipolar linkage peak on chromosome 8q24 using 2,500 genotyped SNPs and 15,000 imputed SNPs.
BPD
Support
ASD, epilepsy/seizures
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
DD, ID
Support
Integrating de novo and inherited variants in 42
ASD
Support
Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.
ASD
Support
Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations
ASD, ID
Support
Genetic and Phenotype Analysis of a Chinese Cohort of Infants and Children With Epilepsy
Epilepsy/seizures
Support
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
ASD, DD
ID
Support
Phenotypic Spectrum in a Family Sharing a Heterozygous KCNQ3 Variant
DD, epilepsy/seizures
ASD, ADHD, ID
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
Variantrecurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense v...
DD
Support
Autism-associated mutations in K V 7 channels induce gating pore current
ASD
Support
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.
ASD
Support
New genes involved in Angelman syndrome-like: Expanding the genetic spectrum
DD, epilepsy/seizures
Highly Cited
A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.
Epilepsy
Recent Recommendation
ASD, epilepsy/seizures
Recent Recommendation
Autism and developmental disability caused by KCNQ3 gain-of-function variants.
DD, ASD or autistic features
Abnormal EEG, absent speech
GEN536R001
translocation
De novo
Simplex
GEN536R002
missense_variant
c.1720C>T
p.Pro574Ser
Familial
Paternal
Unknown
GEN536R003
missense_variant
c.1720C>T
p.Pro574Ser
Familial
Maternal
Multi-generational
GEN536R004
missense_variant
c.929G>T
p.Gly310Val
Familial
Multi-generational
GEN536R005
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R006
missense_variant
c.1964C>T
p.Thr655Met
Familial
Maternal
Multiplex
GEN536R007
missense_variant
c.706C>T
p.Arg236Cys
De novo
GEN536R008
missense_variant
c.296G>A
p.Gly99Asp
De novo
GEN536R009
missense_variant
c.320G>A
p.Arg107Gln
Unknown
GEN536R010
missense_variant
c.328C>T
p.Arg110Cys
Unknown
GEN536R011
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R012
missense_variant
c.329G>A
p.Arg110His
De novo
GEN536R013
missense_variant
c.688C>A
p.Arg230Ser
De novo
GEN536R014
missense_variant
c.689G>A
p.Arg230His
Familial
Maternal
GEN536R015
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R016
missense_variant
c.328C>T
p.Arg110Cys
De novo
GEN536R017
missense_variant
c.689G>A
p.Arg230His
De novo
GEN536R018
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R019
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R020
missense_variant
c.680G>A
p.Arg227Gln
De novo
GEN536R021
missense_variant
c.680G>A
p.Arg227Gln
De novo
GEN536R022
missense_variant
c.328C>T
p.Arg110Cys
De novo
Simplex
GEN536R023
missense_variant
c.329G>A
p.Arg110His
De novo
Simplex
GEN536R024
missense_variant
c.329G>T
p.Arg110Leu
De novo
Simplex
GEN536R025
missense_variant
c.689G>A
p.Arg230His
De novo
GEN536R026
stop_gained
c.927G>A
p.Trp309Ter
Familial
Maternal
GEN536R027
missense_variant
c.569G>A
p.Arg190Gln
De novo
GEN536R028
missense_variant
c.707G>A
p.Arg236His
Familial
Paternal
GEN536R029
missense_variant
c.439G>A
p.Glu147Lys
Familial
Paternal
Multiplex
GEN536R030
missense_variant
c.1582C>T
p.Arg528Cys
Unknown
Not maternal
GEN536R031
missense_variant
c.2561C>T
p.Ser854Leu
Unknown
GEN536R032
missense_variant
c.2561C>T
p.Ser854Leu
Unknown
GEN536R033
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R034
missense_variant
c.656G>A
p.Gly219Asp
De novo
GEN536R035
missense_variant
c.680G>A
p.Arg227Gln
De novo
GEN536R036
missense_variant
c.1411C>T
p.Arg471Cys
Unknown
GEN536R037
missense_variant
c.1850G>C
p.Ser617Thr
Unknown
GEN536R038
missense_variant
c.1850G>C
p.Ser617Thr
Unknown
GEN536R039
missense_variant
c.1918G>A
p.Val640Met
Unknown
GEN536R040
missense_variant
c.1090C>T
p.Arg364Cys
Unknown
GEN536R041
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R042
missense_variant
c.1123G>A
p.Ala375Thr
De novo
GEN536R043
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R044
missense_variant
c.689G>A
p.Arg230His
De novo
GEN536R045
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R046
missense_variant
c.688C>T
p.Arg230Cys
De novo
Simplex
GEN536R047
missense_variant
c.688C>T
p.Arg230Cys
De novo
GEN536R048
missense_variant
c.788C>T
p.Thr263Met
Unknown
GEN536R049
missense_variant
c.1091G>A
p.Arg364His
Familial
Maternal
Multiplex
GEN536R050
missense_variant
c.1403A>G
p.Asn468Ser
Unknown
GEN536R051
synonymous_variant
c.276G>T
p.Pro92%3D
De novo
GEN536R052
missense_variant
c.2270G>A
p.Arg757Gln
De novo
GEN536R053
missense_variant
c.716G>C
p.Arg239Pro
De novo
GEN536C001
upstream_gene_variant
rs2673582
C/T
3512 individuals from 737 families (65 from Johns Hopkins, 672 from NIMH) with bipolar disorder
Discovery
Summary Statistics:
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