KCNAB2

potassium voltage-gated channel subfamily A regulatory beta subunit 2, the group of Aldo-keto reductases|Potassium voltage-gated channel regulatory subunits

Basic information

Region (hg38): 1:5990927-6101193

Links

ENSG00000069424 ∙ NCBI:8514 ∙ OMIM:601142 ∙ HGNC:6229 ∙ Uniprot:Q13303 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNAB2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNAB2 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				16	5	21
missense			24	5	1	30
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				7	2	9
non coding			6	4	4	14
Total	0	0	31	25	10

Variants in KCNAB2

This is a list of pathogenic ClinVar variants found in the KCNAB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-5992257-C-A		Nephronophthisis 4 • Senior-Loken syndrome 4	Uncertain significance (Jan 12, 2018)
1-5992295-T-A		Nephronophthisis 4 • Senior-Loken syndrome 4	Conflicting classifications of pathogenicity (Jan 12, 2018)
1-5992407-G-A		Nephronophthisis 4 • Senior-Loken syndrome 4	Uncertain significance (Jan 13, 2018)
1-5992411-G-T		Nephronophthisis 4 • Senior-Loken syndrome 4	Uncertain significance (Jan 12, 2018)
1-5992430-C-T		Nephronophthisis • Renal dysplasia and retinal aplasia	Uncertain significance (Jun 14, 2016)
1-5992440-C-T		Nephronophthisis • Renal dysplasia and retinal aplasia	Uncertain significance (Jun 14, 2016)
1-5992441-G-A		Renal dysplasia and retinal aplasia • Nephronophthisis	Uncertain significance (Jun 14, 2016)
1-5992442-C-G		Nephronophthisis • Renal dysplasia and retinal aplasia	Uncertain significance (Jun 14, 2016)
1-5992511-G-A			Benign (May 16, 2021)
1-5992521-G-A			Benign (May 13, 2021)
1-6040585-C-T			Likely benign (Nov 01, 2022)
1-6040588-C-T		not specified	Uncertain significance (Feb 22, 2023)
1-6040589-G-A			Likely benign (Feb 01, 2024)
1-6040609-C-T		not specified	Uncertain significance (Jan 24, 2024)
1-6041858-G-A			Likely benign (Jun 14, 2018)
1-6051550-C-T		KCNAB2-related disorder	Likely benign (Jun 08, 2020)
1-6051557-C-G		not specified	Uncertain significance (Apr 13, 2022)
1-6051558-G-A		not specified	Uncertain significance (Oct 06, 2022)
1-6051567-C-T		not specified	Uncertain significance (Aug 12, 2022)
1-6051568-G-A		not specified	Uncertain significance (Jan 08, 2024)
1-6051573-G-A		not specified	Uncertain significance (Feb 28, 2024)
1-6051595-A-G		not specified	Uncertain significance (Jul 26, 2022)
1-6051615-C-T		not specified	Uncertain significance (Jan 24, 2024)
1-6051641-G-C		KCNAB2-related disorder	Benign (Aug 28, 2019)
1-6051648-C-T		not specified	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNAB2	protein_coding	protein_coding	ENST00000378083	15	109728

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.800	0.200	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.60	145	264	0.550	0.0000169	2684
Missense in Polyphen		23	72.748	0.31616		732
Synonymous	0.437	106	112	0.947	0.00000789	806
Loss of Function	3.96	5	27.3	0.183	0.00000125	305

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytoplasmic potassium channel subunit that modulates the characteristics of the channel-forming alpha-subunits (PubMed:7649300, PubMed:11825900). Contributes to the regulation of nerve signaling, and prevents neuronal hyperexcitability (By similarity). Promotes expression of the pore-forming alpha subunits at the cell membrane, and thereby increases channel activity (By similarity). Promotes potassium channel closure via a mechanism that does not involve physical obstruction of the channel pore (PubMed:7649300, PubMed:11825900). Promotes KCNA4 channel closure (PubMed:7649300, PubMed:11825900). Modulates the functional properties of KCNA5 (By similarity). Enhances KCNB2 channel activity (By similarity). Binds NADPH and has NADPH- dependent aldoketoreductase activity (By similarity). Has broad substrate specificity and can catalyze the reduction of methylglyoxal, 9,10-phenanthrenequinone, prostaglandin J2, 4- nitrobenzaldehyde, 4-nitroacetophenone and 4-oxo-trans-2-nonenal (in vitro) (By similarity). {ECO:0000250|UniProtKB:P62482, ECO:0000250|UniProtKB:P62483, ECO:0000269|PubMed:11825900, ECO:0000269|PubMed:7649300}.
• Pathway: Antiarrhythmic Pathway, Pharmacodynamics;Metapathway biotransformation Phase I and II;Neutrophil degranulation;Innate Immune System;Immune System;Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.498
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.37

Haploinsufficiency Scores

• pHI: 0.359
• hipred: Y
• hipred_score: 0.806
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.904

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnab2
• 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); normal phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: kcnab2b
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: hematopoietic progenitor cell differentiation;neutrophil degranulation;neuromuscular process;oxidation-reduction process;NADPH oxidation;potassium ion transmembrane transport;regulation of potassium ion transmembrane transport;regulation of protein localization to cell surface
• Cellular component: cytosol;microtubule;plasma membrane;voltage-gated potassium channel complex;postsynaptic density;membrane;cell junction;extrinsic component of cytoplasmic side of plasma membrane;specific granule membrane;axon terminus;juxtaparanode region of axon;tertiary granule membrane;pinceau fiber
• Molecular function: aldo-keto reductase (NADP) activity;voltage-gated potassium channel activity;potassium channel regulator activity