KCNT1

potassium sodium-activated channel subfamily T member 1, the group of Potassium sodium-activated channel subfamily T

Basic information

Region (hg38): 9:135702185-135795508

Links

ENSG00000107147

∙ NCBI:57582 ∙ OMIM:608167 ∙ HGNC:18865 ∙ Uniprot:Q5JUK3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

developmental and epileptic encephalopathy, 14 (Definitive), mode of inheritance: AD
developmental and epileptic encephalopathy, 14 (Moderate), mode of inheritance: AD
autosomal dominant nocturnal frontal lobe epilepsy 5 (Moderate), mode of inheritance: AD
autosomal dominant nocturnal frontal lobe epilepsy (Supportive), mode of inheritance: AD
malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
autosomal dominant nocturnal frontal lobe epilepsy 5 (Strong), mode of inheritance: AD
developmental and epileptic encephalopathy, 14 (Strong), mode of inheritance: AD
childhood-onset epilepsy syndrome (Definitive), mode of inheritance: AD
malignant migrating partial seizures of infancy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, nocturnal frontal lobe, 5; Developmental and epileptic encephalopathy 14	AD	Neurologic	Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology	Neurologic	18479385; 23086396; 23086397; 23599387; 28331464

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNT1 gene.

Developmental_and_epileptic_encephalopathy,_14 (2024 variants)
Autosomal_dominant_nocturnal_frontal_lobe_epilepsy_5 (1995 variants)
not_provided (616 variants)
Inborn_genetic_diseases (299 variants)
not_specified (245 variants)
KCNT1-related_disorder (67 variants)
Seizure (6 variants)
See_cases (6 variants)
Malignant_migrating_partial_seizures_of_infancy (4 variants)
Epilepsy (2 variants)
Intellectual_disability (2 variants)
Hydrocephalus (1 variants)
Self-limited_epilepsy_with_centrotemporal_spikes (1 variants)
Schizophrenia (1 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
Focal_epilepsy (1 variants)
Neurodevelopmental_abnormality (1 variants)
Morphological_central_nervous_system_abnormality (1 variants)
Developmental_and_epileptic_encephalopathy_97 (1 variants)
Epilepsy_syndrome (1 variants)
Neurodevelopmental_disorder (1 variants)
Developmental_and_epileptic_encephalopathy,_15 (1 variants)
Epileptic_encephalopathy (1 variants)
Autosomal_dominant_nocturnal_frontal_lobe_epilepsy_1 (1 variants)
KCNT1-related_channelopathy (1 variants)
Neurodevelopmental_delay (1 variants)
Hearing_impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020822.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			20 clinvar	584 clinvar	10 clinvar	614
missense	26 clinvar	56 clinvar	736 clinvar	163 clinvar	4 clinvar	985
nonsense		1 clinvar	14 clinvar			15
start loss						0
frameshift		3 clinvar	35 clinvar	4 clinvar		42
splice donor/acceptor (+/-2bp)	1 clinvar		18 clinvar	2 clinvar	1 clinvar	22
Total	27	60	823	753	15

Highest pathogenic variant AF is 0.000013018137

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNT1	protein_coding	protein_coding	ENST00000371757	31	90962

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000276	1.00	125685	0	61	125746	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.86	571	798	0.715	0.0000550	7996
Missense in Polyphen		100	196.28	0.50948		1836
Synonymous	-3.71	447	358	1.25	0.0000274	2417
Loss of Function	4.92	20	61.7	0.324	0.00000282	706

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000393	0.000387
Ashkenazi Jewish	0.00110	0.00109
East Asian	0.000221	0.000217
Finnish	0.0000935	0.0000924
European (Non-Finnish)	0.000256	0.000246
Middle Eastern	0.000221	0.000217
South Asian	0.000134	0.000131
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Outwardly rectifying potassium channel subunit that may coassemble with other Slo-type channel subunits. Activated by high intracellular sodium or chloride levels. Activated upon stimulation of G-protein coupled receptors, such as CHRM1 and GRIA1. May be regulated by calcium in the absence of sodium ions (in vitro) (By similarity). {ECO:0000250}.;
Disease: DISEASE: Epileptic encephalopathy, early infantile, 14 (EIEE14) [MIM:614959]: A rare epileptic encephalopathy of infancy that combines pharmacoresistant seizures with developmental delay. This severe neurologic disorder is characterized by onset in the first 6 months of life of refractory focal seizures and arrest of psychomotor development. Ictal EEG shows discharges that arise randomly from various areas of both hemispheres and migrate from one brain region to another. {ECO:0000269|PubMed:23086397, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:24029078, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epilepsy, nocturnal frontal lobe, 5 (ENFL5) [MIM:615005]: An autosomal dominant focal epilepsy syndrome characterized by childhood onset of clusters of motor seizures during sleep. Some patients may develop behavioral or psychiatric manifestations and/or intellectual disability. The phenotype is more severe than observed in other genetic forms of nocturnal frontal lobe epilepsy. {ECO:0000269|PubMed:23086396}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.105

Intolerance Scores

loftool: 0.577
rvis_EVS: -2.07
rvis_percentile_EVS: 1.62

Haploinsufficiency Scores

pHI: 0.102
hipred: Y
hipred_score: 0.700
ghis: 0.589

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.273

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Kcnt1
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype;

Gene ontology

Biological process: regulation of membrane potential;potassium ion transmembrane transport
Cellular component: plasma membrane;integral component of membrane
Molecular function: intracellular sodium activated potassium channel activity;outward rectifier potassium channel activity