KCNQ1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- KCNQ1 (HGNC:6294) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- potassium voltage-gated channel subfamily Q member 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- LQT, KCNA9
- Alias symbols
- Kv7.1, KCNA8, KVLQT1, JLNS1, LQT1
- %HI
- 23.28(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 0.81(Read more about gnomAD LOEUF score)
- Cytoband
- 11p15.5-p15.4
- Genomic Coordinates
-
GRCh37/hg19: chr11:2466238-2870340 NCBI Ensembl UCSC GRCh38/hg38: chr11:2445008-2849105 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000218.3 ENST00000155840.12 (Read more about MANE Select)
- Function
- Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-17058
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Related Links:
Last Evaluated:
10/13/2020
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- long QT syndrome 1 Monarch
HI Evidence:
-
PUBMED:
26669661
Itoh et al. (2016) A study of multi-national cohort of LQTS families described asymmetry of parental origin in long QT syndrome, with preferential maternal transmission of KCNQ1 variants linked to channel dysfunction. There were a total of 35 LQT1 patients with LOF variants in KCNQ1 gene selected for this study: nonsense (n=6), splice site (n=7), and frameshift variants (n=22) with known or assumed loss of function.
-
PUBMED:
29532034
Huang et al. (2018) studied the mechanisms of KCNQ1 channel dysfunction in LQT. A total of 32 LOF variants (missense or in-frame) were studied with an emphasis on elucidating effects on cell surface expression, protein folding, and structure. More than half of the KCNQ1 LOF mutations examined were seen to destabilize the structure of the voltage sensor domain (VSD), generally accompanied by mistrafficking and degradation by the proteasome, an observation that underscores the growing appreciation that mutation-induced destabilization of membrane proteins may be a common human disease mechanism.
-
PUBMED:
23098067
Stattin et al. (2012) studied 200 Swedish LQT Probands aiming to report the spectrum of LQTS mutations in this Swedish cohort. . Thirty KCNQ1 variants were identified, 9 of which were LOF variants.
HI Evidence Comments:
Heterozygous loss of function variants can cause long QT syndrome type 1. Biallelic variation in KCNQ1 can result in the recessive condition Jervell and Lange-Nielsen syndrome.
Numerous LOF variants in KCNQ1 have been reported in the literature and public/commercial databases. Additional evidence includes:
PMID: 18774102. Barc (2011): Describes a single 2 exon deletion in a patient with long QT syndrome type 1.
PMID: 18774102. Eddy (2008): Describes a single 2 exon deletion resulting in a frameshift and premature stop codon in a patient with long QT syndrome type 1.
PMID:15840476 Tester (2005): Describes 88 patients with long QT syndrome and variants in KCNQ1. Fourteen of these are either nonsense or frameshift mutations.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000011.9)
(NC_000011.10)