KCNA4

potassium voltage-gated channel subfamily A member 4, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 11:30009730-30017030

Previous symbols: [ "KCNA4L" ]

Links

ENSG00000182255 ∙ NCBI:3739 ∙ OMIM:176266 ∙ HGNC:6222 ∙ Uniprot:P22459 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum (Limited), mode of inheritance: AR
• microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum	AR	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; Ophthalmologic	23181898; 27582084

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNA4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNA4 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				5	1	6
missense			25	1		26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	25	6	1

Variants in KCNA4

This is a list of pathogenic ClinVar variants found in the KCNA4 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-30010728-T-C		not specified	Uncertain significance (May 11, 2022)
11-30010758-T-G		not specified	Uncertain significance (Jan 23, 2023)
11-30010760-T-C		not specified	Uncertain significance (Oct 22, 2021)
11-30010855-C-G		Microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum	Uncertain significance (Sep 25, 2019)
11-30010856-T-C		not specified	Uncertain significance (Dec 06, 2024)
11-30010936-C-T			Likely benign (Sep 01, 2023)
11-30011076-C-A		not specified	Uncertain significance (Nov 09, 2022)
11-30011116-G-A			Likely benign (Mar 01, 2023)
11-30011176-C-T			Likely benign (Sep 01, 2022)
11-30011220-T-C		not specified	Uncertain significance (Jul 09, 2024)
11-30011366-A-G		not specified	Uncertain significance (Sep 30, 2024)
11-30011368-G-A			Likely benign (May 01, 2022)
11-30011394-C-G		not specified	Uncertain significance (Sep 11, 2024)
11-30011481-A-C		not specified	Uncertain significance (Aug 07, 2024)
11-30011517-C-T		not specified	Uncertain significance (Nov 24, 2024)
11-30011559-C-A		not specified	Uncertain significance (Nov 26, 2024)
11-30011567-A-C		not specified	Uncertain significance (Dec 21, 2023)
11-30011585-G-C		not specified	Uncertain significance (Jul 29, 2023)
11-30011592-C-T		not specified	Uncertain significance (Nov 13, 2023)
11-30011607-G-A		not specified	Uncertain significance (Oct 25, 2024)
11-30011626-C-G		not specified	Uncertain significance (Oct 17, 2023)
11-30011644-G-A			Benign (Sep 19, 2019)
11-30011659-C-T		not specified	Uncertain significance (Jan 10, 2023)
11-30011660-A-G		not specified	Uncertain significance (Oct 25, 2024)
11-30011730-T-C		not specified	Uncertain significance (Oct 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNA4	protein_coding	protein_coding	ENST00000328224	1	7283

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0167	124625	0	3	124628	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.03	267	378	0.707	0.0000212	4310
Missense in Polyphen		71	163.44	0.4344		1862
Synonymous	-1.55	168	144	1.16	0.00000763	1294
Loss of Function	3.58	1	16.9	0.0593	8.82e-7	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000647	0.0000647
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000884	0.00000884
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:19912772, PubMed:8495559). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). {ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:8495559}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.150

Intolerance Scores

• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.753
• hipred: Y
• hipred_score: 0.769
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.774

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcna4
• Phenotype: 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)

Gene ontology

• Biological process: potassium ion transport;regulation of ion transmembrane transport;protein homooligomerization;potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;integral component of membrane;axon;dendritic spine
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;potassium ion binding