Table 1.

Distribution of K_v7 subunit in the brain and the diseases associated with its pathogenic variants.

Gene	Protein	Primary location	Distribution in the brain		Pathogenic variants
			Regions	Reference	Associated diseases	Reference
KCNQ1	Kv7.1	Heart	CTX, HPF, MB, CB, BS	Casimiro et al., 2001; Goldman et al., 2009. AIBS, THPA	Long QT syndrome 1, JLNS, familial atrial fibrillation epilepsy, SUDEP, ASD, developmental disorder	ClinVar, LOVD, denovo-db
KCNQ2	Kv7.2	Nervous system	CTX, HPF, A, HY, TH, OA, MD, SN, P, MY, CB	Wang et al., 1998; Cooper et al., 2001; Devaux et al., 2004; Klinger et al., 2011; D’Este et al., 2016; Galvin et al., 2020. AIBS, THPA	BFNE, EE, ASD, intellectual disability, developmental disorder, sporadic infantile spasm syndrome	ClinVar, RIKEE, denovo-db
KCNQ3	Kv7.3	Nervous system	CTX, HPF, A, HY, TH, OA, MD, SN, P, MY, CB	Wang et al., 1998; Devaux et al., 2004; Klinger et al., 2011; Galvin et al., 2020. AIBS, THPA	BFNE, EE, ASD, intellectual disability, developmental disorder	ClinVar, RIKEE, denovo-db
KCNQ4	Kv7.4	Inner ear	BS, OA, MD, RN, NA, MY, VTA, P	Hansen et al., 2006; Su et al., 2019. AIBS, THPA	DFNA2, ASD	ClinVar, denovo-db
KCNQ5	Kv7.5	Nervous system	CTX, HPF, BS, CB	Lerche et al., 2000; Schroeder et al., 2000; Tzingounis et al., 2010; Fidzinski et al., 2015; Galvin et al., 2020. AIBS, THPA	EE, ASD, intellectual disability, schizophrenia	ClinVar, RIKEE, denovo-db

Brain regions: CTX, cortex; OA, olfactory areas; HPF, hippocampal formation; A, amygdala; NA, nucleus accumbens; BS, brain stem; TH, thalamus; HY, hypothalamus; MB, midbrain; RN, raphe nuclei; SN, substantia nigra; VTA, ventral tegmental area; PAL, pallidum; HB, hindbrain; CB, cerebellum; P, pons; MY, medulla. K_v7 channelopathies: JLNS, Jervell and Lange-Nielsen syndrome; SUDEP, sudden unexpected death in epilepsy; BFNE, benign familial neonatal epilepsy; EE, epileptic encephalopathy; ASD, autism spectrum disorder; DFNA2, nonsyndromic sensorineural deafness type 2. Database website: Allen Institute for Brain Science (AIBS, https://alleninstitute.org/what-we-do/brain-science/), The Human Protein Atlas (THPA, https://www.proteinatlas.org/), ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), Leiden Open Variation Database (LOVD, https://research.cchmc.org/LOVD2/home.php), denovo-db (http://denovo-db.gs.washington.edu/denovo-db/index.jsp), and Rational Intervention for KCNQ2/3 Epileptic Encephalopathy (RIKEE, https://www.rikee.org/).