KCNH5

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

Basic information

Region (hg38): 14:62699464-63102037

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
developmental and epileptic encephalopathy 112 (Strong), 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.

Developmental_and_epileptic_encephalopathy (693 variants)
Inborn_genetic_diseases (74 variants)
not_provided (55 variants)
not_specified (13 variants)
Developmental_and_epileptic_encephalopathy_112 (8 variants)
KCNH5-related_disorder (7 variants)
Developmental_and_epileptic_encephalopathy,_12 (6 variants)
Metabolic_crises,_recurrent,_with_variable_encephalomyopathic_features_and_neurologic_regression (2 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. These statistics are base on transcript: NM_000139318.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	200 clinvar	10 clinvar	213
missense	4 clinvar	5 clinvar	329 clinvar	40 clinvar	32 clinvar	410
nonsense			13 clinvar	4 clinvar		17
start loss						0
frameshift			12 clinvar	1 clinvar		13
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	4	5	361	245	42

Highest pathogenic variant AF is 0.0000020522166

Loading clinvar variants...

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