KCNN3

potassium calcium-activated channel subfamily N member 3, the group of Potassium calcium-activated channels

Basic information

Region (hg38): 1:154697454-154870281

Links

ENSG00000143603 ∙ NCBI:3782 ∙ OMIM:602983 ∙ HGNC:6292 ∙ Uniprot:Q9UGI6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (Limited), mode of inheritance: Unknown
• zimmermann-laband syndrome 3 (Moderate), mode of inheritance: AD
• Zimmermann-Laband syndrome (Supportive), mode of inheritance: AR
• zimmermann-laband syndrome 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Zimmermann-Laband syndrome 3	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	Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic	31155282

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNN3 gene.

• not provided (35 variants)
• not specified (24 variants)
• Inborn genetic diseases (18 variants)
• Zimmermann-laband syndrome 3 (12 variants)
• KCNN3-related condition (1 variants)
• Esophageal atresia;Pyloric stenosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNN3 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				3	2	5
missense	1	1	36	7	1	46
nonsense			1			1
start loss						0
frameshift						0
inframe indel				4	18	22
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding			1		1	2
Total	1	1	39	14	22

Variants in KCNN3

This is a list of pathogenic ClinVar variants found in the KCNN3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-154708000-C-T			Likely benign (May 01, 2022)
1-154708026-C-A		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
1-154708031-A-G		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
1-154708065-C-A			Uncertain significance (Feb 17, 2020)
1-154708075-G-A			Likely benign (May 01, 2023)
1-154708083-C-G		Inborn genetic diseases	Likely benign (Nov 17, 2023)
1-154708092-C-T		Zimmermann-laband syndrome 3	Uncertain significance (May 15, 2020)
1-154708113-G-A		Zimmermann-laband syndrome 3	Uncertain significance (Dec 08, 2021)
1-154708200-T-G		Inborn genetic diseases	Uncertain significance (Mar 29, 2022)
1-154714919-T-C		Zimmermann-laband syndrome 3	Uncertain significance (May 18, 2022)
1-154714922-C-T		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
1-154714976-G-A			Uncertain significance (Feb 01, 2023)
1-154722857-G-A		Zimmermann-laband syndrome 3	Uncertain significance (Jun 10, 2021)
1-154725965-G-A			Uncertain significance (Jan 05, 2021)
1-154726011-C-T		Zimmermann-laband syndrome 3	Pathogenic (Nov 18, 2020)
1-154733022-C-G			Uncertain significance (Feb 09, 2022)
1-154733048-G-T			Likely benign (Feb 01, 2024)
1-154737064-A-C			Benign (Apr 01, 2024)
1-154771973-A-G			Uncertain significance (Jun 09, 2022)
1-154771974-C-A		Malignant tumor of prostate	Uncertain significance (-)
1-154771987-C-T			Uncertain significance (Dec 29, 2022)
1-154771991-C-T			Likely benign (Jul 01, 2023)
1-154772047-G-C		Inborn genetic diseases	Uncertain significance (Apr 03, 2023)
1-154772052-G-C			Uncertain significance (Mar 21, 2023)
1-154772072-T-C		KCNN3-related disorder	Uncertain significance (Sep 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNN3	protein_coding	protein_coding	ENST00000271915	8	172826

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.972	0.0277	125703	32	13	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.33	245	442	0.555	0.0000265	4808
Missense in Polyphen		66	152.56	0.43262		1753
Synonymous	0.221	190	194	0.980	0.0000127	1494
Loss of Function	4.27	4	28.7	0.139	0.00000152	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000979	0.000979
Ashkenazi Jewish	0.000878	0.000198
East Asian	0.000911	0.000272
Finnish	0.000348	0.000185
European (Non-Finnish)	0.000375	0.000123
Middle Eastern	0.000911	0.000272
South Asian	0.00132	0.000294
Other	0.00227	0.000489

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: Insulin secretion - Homo sapiens (human);Neuronal System;Ca2+ activated K+ channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.0697
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.54

Haploinsufficiency Scores

• pHI: 0.200
• hipred: Y
• hipred_score: 0.658
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.329

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnn3
• 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); 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); reproductive system phenotype; respiratory system phenotype

Gene ontology

• Biological process: potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of membrane;neuron projection;neuronal cell body
• Molecular function: calmodulin binding;small conductance calcium-activated potassium channel activity