KCNT2

potassium sodium-activated channel subfamily T member 2, the group of Potassium sodium-activated channel subfamily T |MicroRNA protein coding host genes

Basic information

Region (hg38): 1:196225779-196609225

Links

ENSG00000162687 ∙ NCBI:343450 ∙ OMIM:610044 ∙ HGNC:18866 ∙ Uniprot:Q6UVM3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 57 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 57 (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy, 57 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epileptic encephalopathy, early infantile, 57	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	Neurologic	29069600

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNT2 gene.

• not_provided (114 variants)
• Inborn_genetic_diseases (80 variants)
• Developmental_and_epileptic_encephalopathy,_57 (44 variants)
• KCNT2-related_disorder (19 variants)
• not_specified (8 variants)
• Seizure (3 variants)
• Neurodevelopmental_delay (1 variants)
• Mild_global_developmental_delay (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000198503.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	16		18
missense	2	7	173	16		198
nonsense	1	2	4			7
start loss						0
frameshift	1	3	4			8
splice donor/acceptor (+/-2bp)		1	3			4
Total	4	13	186	32	0

Highest pathogenic variant AF is 0.00000496484

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNT2	protein_coding	protein_coding	ENST00000294725	28	383447

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0417	0.958	125724	0	23	125747	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.56	340	582	0.585	0.0000282	7452
Missense in Polyphen		108	253.36	0.42627		3318
Synonymous	-1.10	223	203	1.10	0.0000101	2093
Loss of Function	5.74	17	68.1	0.250	0.00000384	812

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000182	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000278	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000891	0.0000879
Middle Eastern	0.000278	0.000272
South Asian	0.0000658	0.0000653
Other	0.000175	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Outward rectifying potassium channel. Produces rapidly activating outward rectifier K(+) currents. Activated by high intracellular sodium and chloride levels (PubMed:14684870, PubMed:16687497, PubMed:29069600). Channel activity is inhibited by ATP and by inhalation anesthetics, such as isoflurane (PubMed:16687497) (By similarity). Inhibited upon stimulation of G-protein coupled receptors, such as CHRM1 and GRM1 (PubMed:16687497). {ECO:0000250|UniProtKB:Q6UVM4, ECO:0000269|PubMed:14684870, ECO:0000269|PubMed:16687497, ECO:0000269|PubMed:29069600}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 57 (EIEE57) [MIM:617771]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE57 is an autosomal dominant condition. {ECO:0000269|PubMed:29069600}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.144

Intolerance Scores

• rvis_EVS: -1.29
• rvis_percentile_EVS: 5.08

Haploinsufficiency Scores

• pHI: 0.568
• hipred: Y
• hipred_score: 0.725
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.450

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnt2
• Phenotype: 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); normal phenotype

Gene ontology

• Biological process: regulation of membrane potential;potassium ion export across plasma membrane
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: intracellular sodium activated potassium channel activity;ATP binding;outward rectifier potassium channel activity;chloride-activated potassium channel activity