KCNQ5

potassium voltage-gated channel subfamily Q member 5, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 6:72621792-73198853

Links

ENSG00000185760 ∙ NCBI:56479 ∙ OMIM:607357 ∙ HGNC:6299 ∙ Uniprot:Q9NR82 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 46 (Strong), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 46	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	28669405

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNQ5 gene.

• not provided (7 variants)
• Intellectual disability, autosomal dominant 46 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNQ5 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	175	19	197
missense	4	6	214	29	53	306
nonsense	1	1	7			9
start loss	1					1
frameshift	3	1	8	1		13
inframe indel			6	3		9
splice donor/acceptor (+/-2bp)			1			1
splice region			4	14	3	21
non coding		1	11	53	7	72
Total	9	9	250	261	79

Variants in KCNQ5

This is a list of pathogenic ClinVar variants found in the KCNQ5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-72622190-A-G			Uncertain significance (Apr 01, 2024)
6-72622191-T-C			Pathogenic (Jul 20, 2023)
6-72622194-CCCG-C			Uncertain significance (Sep 01, 2022)
6-72622196-C-A		Inborn genetic diseases • Intellectual disability • Intellectual disability, autosomal dominant 46	Conflicting classifications of pathogenicity (May 01, 2024)
6-72622197-G-T		Inborn genetic diseases • Intellectual disability, autosomal dominant 46	Uncertain significance (Jan 07, 2024)
6-72622203-A-G			Uncertain significance (Jan 21, 2023)
6-72622204-C-G			Uncertain significance (Nov 03, 2021)
6-72622204-C-T			Likely benign (Mar 02, 2023)
6-72622207-G-C			Likely benign (Oct 23, 2022)
6-72622208-G-A			Uncertain significance (Oct 28, 2021)
6-72622211-G-A		Intellectual disability • KCNQ5-related disorder • Inborn genetic diseases	Benign/Likely benign (Nov 01, 2024)
6-72622212-G-A			Uncertain significance (Nov 27, 2023)
6-72622222-C-T			Likely benign (Dec 11, 2023)
6-72622225-C-T			Likely benign (Aug 02, 2023)
6-72622226-G-A		not specified	Conflicting classifications of pathogenicity (Sep 16, 2024)
6-72622230-C-T			Uncertain significance (May 16, 2021)
6-72622231-C-G			Likely benign (Apr 18, 2023)
6-72622231-C-T			Likely benign (Nov 18, 2023)
6-72622232-G-C			Uncertain significance (Sep 12, 2022)
6-72622234-G-T			Likely benign (Nov 01, 2024)
6-72622238-T-C		Intellectual disability, autosomal dominant 46	Uncertain significance (Jun 21, 2019)
6-72622240-G-A			Pathogenic (Aug 14, 2023)
6-72622240-G-C		KCNQ5-related disorder	Likely benign (Nov 12, 2023)
6-72622249-C-A			Uncertain significance (Jan 20, 2024)
6-72622250-G-T			Uncertain significance (Dec 21, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNQ5	protein_coding	protein_coding	ENST00000342056	15	577055

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.980	0.0199	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.32	289	497	0.581	0.0000276	6134
Missense in Polyphen		45	173.74	0.259		2005
Synonymous	-1.80	219	188	1.17	0.0000109	1926
Loss of Function	5.29	8	47.2	0.169	0.00000294	513

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000153	0.000152
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00116	0.00116
European (Non-Finnish)	0.0000794	0.0000791
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. Therefore, it is important in the regulation of neuronal excitability. May contribute, with other potassium channels, to the molecular diversity of a heterogeneous population of M- channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current. Insensitive to tetraethylammonium, but inhibited by barium, linopirdine and XE991. Activated by niflumic acid and the anticonvulsant retigabine. As the native M-channel, the potassium channel composed of KCNQ3 and KCNQ5 is also suppressed by activation of the muscarinic acetylcholine receptor CHRM1. {ECO:0000269|PubMed:10787416, ECO:0000269|PubMed:11159685, ECO:0000269|PubMed:28669405}.
• Disease: DISEASE: Mental retardation, autosomal dominant 46 (MRD46) [MIM:617601]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD46 patients manifest developmental delay and mild to moderate intellectual disability. {ECO:0000269|PubMed:28669405}. 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: 0.118

Intolerance Scores

• loftool: 0.0121
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.08

Haploinsufficiency Scores

• pHI: 0.109
• hipred: Y
• hipred_score: 0.717
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.760

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnq5
• 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)

Gene ontology

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