KCNT1

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

Basic information

Region (hg38): 9:135702184-135795508

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

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;Autosomal dominant nocturnal frontal lobe epilepsy 5 (1198 variants)
• not provided (643 variants)
• Developmental and epileptic encephalopathy, 14 (359 variants)
• Autosomal dominant nocturnal frontal lobe epilepsy 5 (337 variants)
• Autosomal dominant nocturnal frontal lobe epilepsy 5;Developmental and epileptic encephalopathy, 14 (326 variants)
• not specified (226 variants)
• Inborn genetic diseases (223 variants)
• KCNT1-related condition (10 variants)
• See cases (5 variants)
• Seizure (5 variants)
• Malignant migrating partial seizures of infancy (3 variants)
• Neurodevelopmental delay (2 variants)
• Epileptic encephalopathy (1 variants)
• Focal epilepsy (1 variants)
• Hydrocephalus (1 variants)
• KCNT1-related channelopathy (1 variants)
• Epilepsy (1 variants)
• Neurodevelopmental disorder (1 variants)
• Epilepsy syndrome (1 variants)
• Childhood epilepsy with centrotemporal spikes (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	444	9	465
missense	19	41	531	88	2	681
nonsense		1	8			9
start loss						0
frameshift			22	3		25
inframe indel			20			20
splice donor/acceptor (+/-2bp)	1		11	1	1	14
splice region			42	84	9	135
non coding			12	303	124	439
Total	20	42	616	839	136

Highest pathogenic variant AF is 0.0000329

Variants in KCNT1

This is a list of pathogenic ClinVar variants found in the KCNT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-135702219-C-T			Likely benign (May 14, 2018)
9-135702221-C-T		not specified	Likely benign (Feb 18, 2016)
9-135702232-C-T		not specified	Likely benign (Jul 21, 2016)
9-135702243-C-T		not specified	Likely benign (Nov 27, 2017)
9-135702258-C-A		Developmental and epileptic encephalopathy, 14 • Autosomal dominant nocturnal frontal lobe epilepsy 5 • Inborn genetic diseases	Benign (Mar 15, 2022)
9-135702262-C-G		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Feb 01, 2024)
9-135702262-C-T		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Uncertain significance (Jul 19, 2022)
9-135702265-C-T		Autosomal dominant nocturnal frontal lobe epilepsy 5;Developmental and epileptic encephalopathy, 14	Uncertain significance (Feb 28, 2023)
9-135702267-C-T		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Dec 14, 2022)
9-135702268-C-T		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Oct 03, 2023)
9-135702269-C-G		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Aug 09, 2022)
9-135702273-C-G		Autosomal dominant nocturnal frontal lobe epilepsy 5;Developmental and epileptic encephalopathy, 14	Uncertain significance (Sep 27, 2023)
9-135702273-C-T		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Oct 18, 2023)
9-135702274-G-A		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Dec 19, 2023)
9-135702274-G-C		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5 • Inborn genetic diseases	Uncertain significance (Jul 10, 2023)
9-135702277-GC-G		Developmental and epileptic encephalopathy, 14	Likely benign (Jul 26, 2022)
9-135702278-C-T		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Uncertain significance (Mar 11, 2023)
9-135702280-C-G		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Jan 27, 2024)
9-135702284-C-A		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Uncertain significance (Dec 19, 2023)
9-135702284-C-T		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Uncertain significance (Jul 14, 2023)
9-135702286-C-G		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Uncertain significance (Dec 25, 2021)
9-135702287-C-CG		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Uncertain significance (Nov 27, 2023)
9-135702288-G-A		not specified • Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5 • Autosomal dominant nocturnal frontal lobe epilepsy 5 • Developmental and epileptic encephalopathy, 14 • Inborn genetic diseases	Benign (Feb 01, 2024)
9-135702288-G-C		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Aug 16, 2022)
9-135702288-G-T		Developmental and epileptic encephalopathy, 14;Autosomal dominant nocturnal frontal lobe epilepsy 5	Likely benign (Oct 28, 2021)

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