KCNH5

potassium voltage-gated channel subfamily H member 5, the group of Potassium voltage-gated channels|PAS domain containing

Basic information

Region (hg38): 14:62699463-63102037

Links

ENSG00000140015 ∙ NCBI:27133 ∙ OMIM:605716 ∙ HGNC:6254 ∙ Uniprot:Q8NCM2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• infantile-onset epilepsy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 112	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	23647072; 32725632; 34136434; 35874597; 36307226
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNH5 gene.

• Early infantile epileptic encephalopathy with suppression bursts (536 variants)
• Inborn genetic diseases (25 variants)
• not provided (18 variants)
• not specified (5 variants)
• Developmental and epileptic encephalopathy 112 (3 variants)
• Developmental and epileptic encephalopathy, 12 (3 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNH5 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				153	12	165
missense	1	2	213	27	37	280
nonsense			7	4		11
start loss						0
frameshift			7	1		8
inframe indel			2			2
splice donor/acceptor (+/-2bp)			2			2
splice region			7	17	5	29
non coding				45	9	54
Total	1	2	231	230	58

Highest pathogenic variant AF is 0.00000668

Variants in KCNH5

This is a list of pathogenic ClinVar variants found in the KCNH5 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-62707521-T-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 16, 2023)
14-62707522-C-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Nov 24, 2023)
14-62707524-T-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 02, 2018)
14-62707527-T-C		Early infantile epileptic encephalopathy with suppression bursts	Benign (Mar 18, 2020)
14-62707533-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 04, 2022)
14-62707539-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jun 26, 2022)
14-62707540-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jun 16, 2023)
14-62707548-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 27, 2021)
14-62707554-G-C		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jul 13, 2023)
14-62707562-A-G		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Mar 19, 2022)
14-62707584-TG-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (May 25, 2022)
14-62707584-T-TG		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Jan 29, 2024)
14-62707585-G-C		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Jun 25, 2023)
14-62707585-G-T		Early infantile epileptic encephalopathy with suppression bursts	Benign (Jan 22, 2024)
14-62707586-G-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Aug 19, 2021)
14-62707586-G-C		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Mar 26, 2023)
14-62707586-G-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Sep 10, 2023)
14-62707587-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (May 25, 2023)
14-62707587-G-T		Inborn genetic diseases	Uncertain significance (Oct 22, 2021)
14-62707591-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 17, 2023)
14-62707592-T-A			Likely benign (Apr 01, 2022)
14-62707597-G-A		not specified	Uncertain significance (Mar 13, 2024)
14-62707603-G-A		Early infantile epileptic encephalopathy with suppression bursts • Inborn genetic diseases	Uncertain significance (Oct 12, 2022)
14-62707609-G-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Oct 15, 2022)
14-62707615-T-C		Early infantile epileptic encephalopathy with suppression bursts	Benign (Nov 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNH5	protein_coding	protein_coding	ENST00000322893	11	395469

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0197	0.980	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.51	390	557	0.701	0.0000306	6509
Missense in Polyphen		127	243.38	0.52181		2886
Synonymous	0.326	209	215	0.972	0.0000126	1904
Loss of Function	4.47	12	44.0	0.273	0.00000254	505

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000906	0.0000904
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000416	0.000416
European (Non-Finnish)	0.000186	0.000141
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a non-inactivating outward rectifying current. Channel properties may be modulated by cAMP and subunit assembly.
• Pathway: Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.0324
• rvis_EVS: -1.46
• rvis_percentile_EVS: 3.81

Haploinsufficiency Scores

• pHI: 0.601
• hipred: Y
• hipred_score: 0.822
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.792

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnh5
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of G2/M transition of mitotic cell cycle;regulation of ion transmembrane transport;regulation of membrane potential;potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface
• Molecular function: voltage-gated potassium channel activity;calmodulin binding;ion channel binding;protein heterodimerization activity