GeneBe

KCNT2

protein-coding

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

Gene summary

Enables chloride-activated potassium channel activity and intracellular sodium-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_198503.5

Inheritance

AD

ClinVar variants

P:21U:270B:62

Top phenotype

Epileptic encephalopathy, early infantile, 57

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr1:196,225,779-196,609,225

External References & Databases

Ensembl (ENSG00000162687)NCBI Gene (343450)OMIM (610044)HGNC:18866GenCCUniProt (Q6UVM3)AlphaFoldClinVar (KCNT2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~383.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 57STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0033366

Submitter: Labcorp Genetics (formerly Invitae)

complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: ClinGen

*KCNT2* was first reported in relation to complex neurodevelopmental disorder in 2017 (Gururaj, et.al. PMID: 29069600). This condition is characterized by early-onset seizures, global developmental delays, dysmorphic features, short stature, and neurological features such as hypotonia, spasticity, and poor visual attention. Included in this curation are 17 total variants (1 small deletion and 16 missense variants). They have been reported in 22 probands in 8 publications (PMIDs: 38510274, 37062836, 29740868, 34061450, 34276763, 29069600, 32773162, 32931186). More evidence is available in the literature, but the maximum score for genetic evidence (12pts.) has been reached. The mechanism of pathogenicity is attributed to an alteration of channel electrophysiology, including some studies that suggest a gain-of-function mechanism (PMID: 29069600). There are published functional studies showing a decrease in channel activity for certain variants (PMID: 37062836) and two truncating variants have been published in the literature (PMID: 32038177), however they have not been included in this curation and haploinsufficiency as a mechanism for this disease association is unclear at this time. In summary, there is definitive evidence supporting the relationship between *KCNT2* and complex neurodevelopmental disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Epilepsy GCEP on the meeting date June 16, 2026 (SOP Version 12).

developmental and epileptic encephalopathy, 57STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0033366

Submitter: PanelApp Australia

developmental and epileptic encephalopathy, 57LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0033366

Submitter: G2P

developmental and epileptic encephalopathy, 57MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0033366

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Epileptic encephalopathy, early infantile, 57AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing

Refs: 29069600Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNT2 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 181
Inborn genetic diseasesTotal: 99
not specifiedTotal: 72
Developmental and epileptic encephalopathy, 57Total: 53
KCNT2-related disorderTotal: 29
SeizureTotal: 3
Neurodevelopmental delayTotal: 1
Mild global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198503.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
6
clinvar
40
clinvar
 46
missense
3
clinvar
7
clinvar
235
clinvar
22
clinvar
 267
nonsense
5
clinvar
9
clinvar
 14
start loss
0
frameshift
1
clinvar
4
clinvar
12
clinvar
 17
splice donor/acceptor (+/-2bp)
1
clinvar
8
clinvar
 9
Total417270620353

Highest pathogenic variant AF is 0.000003460744

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_198503.5RefSeqNP_940905.228MANE Select
ENST00000294725.14EnsemblENSP00000294725.828MANE Select
NM_001287819.3RefSeqNP_001274748.127Standard
NM_001287820.3RefSeqNP_001274749.127Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • regulation of membrane potential
  • potassium ion export across plasma membrane

Molecular Function

  • intracellular sodium activated potassium channel activity
  • ATP binding
  • outward rectifier potassium channel activity
  • chloride-activated potassium channel activity

Cellular Component

  • plasma membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000294725
Coding exons
28
Length
383447
Individuals with no LoFs
125724
Homozygous LoFs
0
Heterozygous LoFs
23
Defined
125747
p
0.0000915
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.563405820.5850.00002827452
Missense (PolyPhen)108253.360.426273318
Synonymous-1.102232031.100.00001012093
Loss of Function5.741768.10.2500.00000384812

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.000280.00027rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000890.000088rare
South Asian0.0000660.000065rare
Other0.000170.00016rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.450

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.