KCNN2

potassium calcium-activated channel subfamily N member 2, the group of Potassium calcium-activated channels

Basic information

Region (hg38): 5:114055926-114496500

Links

ENSG00000080709 ∙ NCBI:3781 ∙ OMIM:605879 ∙ HGNC:6291 ∙ Uniprot:Q9H2S1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with or without variable movement or behavioral abnormalities (Strong), mode of inheritance: AD
• neurodevelopmental disorder with or without variable movement or behavioral abnormalities (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 34, myoclonic; Neurodevelopmental disorder with or without variable movement or behavioral abnormalities	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	32212350; 33242881

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNN2 gene.

• not_provided (68 variants)
• Inborn_genetic_diseases (52 variants)
• Neurodevelopmental_disorder_with_or_without_variable_movement_or_behavioral_abnormalities (31 variants)
• Global_developmental_delay (10 variants)
• Dystonia_34,_myoclonic (9 variants)
• not_specified (7 variants)
• Autistic_behavior (6 variants)
• KCNN2-related_disorder (4 variants)
• Intellectual_disability,_mild (3 variants)
• Intellectual_disability (3 variants)
• Cerebellar_ataxia (3 variants)
• Motor_tics (3 variants)
• Intellectual_disability,_moderate (2 variants)
• Seizure (2 variants)
• Neurodevelopmental_disorder (1 variants)
• KCNN2-related_Neurodevelopmental_movement_disorder (1 variants)
• Intellectual_disability,_severe (1 variants)
• Bradykinesia (1 variants)
• Dyskinesia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021614.4. 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				9	1	10
missense	2	7	109	8		126
nonsense	2	1	1			4
start loss						0
frameshift	3	1	5			9
splice donor/acceptor (+/-2bp)		1	2			3
Total	7	10	117	17	1

Highest pathogenic variant AF is 6.84724e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNN2	protein_coding	protein_coding	ENST00000512097	8	135696

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00901	125674	0	17	125691	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.29	214	331	0.646	0.0000166	3772
Missense in Polyphen		56	127.92	0.43777		1556
Synonymous	-2.31	166	132	1.26	0.00000698	1160
Loss of Function	4.05	2	22.9	0.0872	0.00000116	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000295	0.0000295
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000218
Finnish	0.00	0.00
European (Non-Finnish)	0.0000533	0.0000440
Middle Eastern	0.000219	0.000218
South Asian	0.000169	0.000163
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
• Pathway: Serotonergic synapse - Homo sapiens (human);Bile secretion - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Neuronal System;Ca2+ activated K+ channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• rvis_EVS: -0.85
• rvis_percentile_EVS: 11.06

Haploinsufficiency Scores

• pHI: 0.849
• hipred: Y
• hipred_score: 0.875
• ghis: 0.599

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.662

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnn2
• 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); growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system 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)

Gene ontology

• Biological process: potassium ion transport;potassium ion transmembrane transport;membrane repolarization during atrial cardiac muscle cell action potential;regulation of potassium ion transmembrane transport
• Cellular component: plasma membrane;cell surface;integral component of membrane;Z disc;neuron projection;neuronal cell body;dendritic spine
• Molecular function: protein binding;calmodulin binding;calcium-activated potassium channel activity;small conductance calcium-activated potassium channel activity;protein domain specific binding;protein homodimerization activity;alpha-actinin binding