KCNQ4

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

Basic information

Region (hg38): 1:40783787-40840452

Previous symbols: [ "DFNA2" ]

Links

ENSG00000117013 ∙ NCBI:9132 ∙ OMIM:603537 ∙ HGNC:6298 ∙ Uniprot:P56696 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 2A (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 2A (Strong), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 2A	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	Audiologic/Otolaryngologic	10369879; 10025409; 16596322; 18030493; 23399560; 23443030; 23451214; 23717403
The onset of deafness appears postlingual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNQ4 gene.

• not provided (7 variants)
• Autosomal dominant nonsyndromic hearing loss 2A (6 variants)
• Rare genetic deafness (3 variants)
• Nonsyndromic genetic hearing loss (2 variants)
• Bilateral sensorineural hearing impairment (1 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNQ4 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			2	45	9	56
missense	6	9	135	7	4	161
nonsense	1	2	2			5
start loss						0
frameshift	2	2	1			5
inframe indel	1		5			6
splice donor/acceptor (+/-2bp)		3				3
splice region			8	5		13
non coding			2	39	38	79
Total	10	16	147	91	51

Highest pathogenic variant AF is 0.0000135

Variants in KCNQ4

This is a list of pathogenic ClinVar variants found in the KCNQ4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-40784080-G-T			Conflicting classifications of pathogenicity (Jun 04, 2018)
1-40784108-C-T			Likely benign (Dec 30, 2023)
1-40784120-C-T			Likely benign (Jul 17, 2023)
1-40784121-G-A		Autosomal dominant nonsyndromic hearing loss 2A • Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
1-40784129-T-TCCCCCGCCCGGGGACGC			Pathogenic (Sep 20, 2023)
1-40784143-A-C		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
1-40784145-GC-AG			Uncertain significance (Jun 14, 2022)
1-40784146-C-T			Uncertain significance (Apr 12, 2023)
1-40784158-A-C		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
1-40784173-C-G			Uncertain significance (Feb 21, 2023)
1-40784174-G-A			Uncertain significance (Apr 26, 2021)
1-40784200-C-CG			Uncertain significance (Jan 30, 2024)
1-40784203-G-A			Uncertain significance (Nov 29, 2023)
1-40784230-G-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
1-40784233-T-C		Autosomal dominant nonsyndromic hearing loss 2A	Pathogenic/Likely pathogenic (Jun 21, 2024)
1-40784236-T-A		Inborn genetic diseases	Uncertain significance (Apr 27, 2022)
1-40784242-G-A		not specified	Likely benign (Dec 06, 2017)
1-40784248-T-A			Uncertain significance (Apr 02, 2020)
1-40784262-C-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
1-40784268-C-T		Inborn genetic diseases	Uncertain significance (Aug 10, 2021)
1-40784269-C-T		Autosomal dominant nonsyndromic hearing loss 2A • KCNQ4-related disorder	Benign/Likely benign (Dec 11, 2023)
1-40784271-G-C		Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
1-40784274-C-T		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
1-40784275-C-T			Uncertain significance (Dec 16, 2023)
1-40784274-C-CCGGGCTCCGGCT			Conflicting classifications of pathogenicity (Aug 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNQ4	protein_coding	protein_coding	ENST00000347132	14	56441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.468	0.532	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.17	288	412	0.699	0.0000279	4390
Missense in Polyphen		115	197.33	0.58279		2035
Synonymous	1.35	156	179	0.871	0.0000128	1465
Loss of Function	4.10	7	32.1	0.218	0.00000163	343

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000922	0.0000922
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000939	0.0000924
European (Non-Finnish)	0.000119	0.000114
Middle Eastern	0.000272	0.000272
South Asian	0.0000331	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.
• Disease: DISEASE: Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378, ECO:0000269|PubMed:21242547}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cholinergic synapse - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;ion channels and their functional role in vascular endothelium;Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.0424
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.76

Haploinsufficiency Scores

• pHI: 0.129
• hipred: Y
• hipred_score: 0.715
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.311

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnq4
• Phenotype: hearing/vestibular/ear 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;sensory perception of sound;regulation of ion transmembrane transport;inner ear morphogenesis;potassium ion transmembrane transport
• Cellular component: plasma membrane;voltage-gated potassium channel complex;basal plasma membrane;integral component of membrane
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;potassium channel activity;protein binding;calmodulin binding