KCNQ2
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KCNQ2 (HGNC:6296) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
potassium voltage-gated channel subfamily Q member 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
EBN, EBN1
Alias symbols
Kv7.2, ENB1, BFNC, KCNA11, HNSPC
%HI
39.78(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.3(Read more about gnomAD LOEUF score)
Cytoband
20q13.33
Genomic Coordinates
GRCh37/hg19: chr20:62031561-62104008 NCBI Ensembl UCSC
GRCh38/hg38: chr20:63400208-63472655 NCBI Ensembl UCSC
MANE Select Transcript
NM_172107.4 ENST00000359125.7 (Read more about MANE Select)
Function
Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvuls... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-34444
ClinGen Curation ID:
CCID:007356
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
07/18/2013

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • seizures, benign familial neonatal, 1 Monarch
HI Evidence:
  • PUBMED: 17675531
    Heron et al. (2007): Describes 3 intragenic deletions (all removing multiple continuous exons) of KCNQ2 detected amongst families affected with benign familial neonatal seizures (BFNS). An intragenic duplication of exons 3-12 was also described. These mutations were also detected in all affected relatives of each proband.
  • PUBMED: 14534157
    Singh et al. (2003): Describes a deletion extending from intron 8 of KCNQ2 through 22.1 kb past the KCNQ2 stop codon, deleting the last nine exons of KCNQ2. The authors propose that the "likely disease‐causing mechanism is haploinsufficiency of the KCNQ2 protein, because mRNA produced from the deleted KCNQ2 allele lacks the poly A tail and is potentially degraded rapidly." Also describe 4 additional nonsense mutations detected in individuals with BFNS. The authors state that "these mutations cause a variable loss of function, and selective effects on the biophysical properties of KCNQ2/KCNQ3 heteromultimeric channels." Of note, this paper also describes "the first dominant negative mutation in KCNQ2 that has a phenotype of neonatal seizures without permanent clinical CNS impairment" (867insGGGCC).
HI Evidence Comments:
From Singh et al. (2003) (PMID:14534157): "Expression of a few of the mutations identified to date suggests that a partial loss of function in potassium current is sufficient to produce an epilepsy phenotype, and dominant negative mutations in either KCNQ2 or KCNQ3 may lead to a more severe phenotype (Jentsch, 2000, PMID:11252765)

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000020.10) (NC_000020.11)