KCNH3

potassium voltage-gated channel subfamily H member 3, the group of Potassium voltage-gated channels|PAS domain containing

Basic information

Region (hg38): 12:49539030-49558337

Links

ENSG00000135519 ∙ NCBI:23416 ∙ OMIM:604527 ∙ HGNC:6252 ∙ Uniprot:Q9ULD8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNH3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNH3 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	5
missense			47	3		50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	47	3	6

Variants in KCNH3

This is a list of pathogenic ClinVar variants found in the KCNH3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-49539490-C-T			Uncertain significance (Aug 05, 2020)
12-49541073-G-A		not specified	Uncertain significance (Mar 07, 2023)
12-49542717-C-T		not specified	Uncertain significance (Jun 05, 2023)
12-49542732-G-A		not specified	Uncertain significance (Jan 03, 2024)
12-49542744-G-A		not specified	Uncertain significance (Apr 28, 2022)
12-49542795-G-A		not specified	Uncertain significance (Jan 05, 2022)
12-49542820-G-A		not specified	Uncertain significance (Aug 22, 2023)
12-49543335-C-T		not specified	Uncertain significance (Jun 13, 2022)
12-49543431-G-A		not specified	Uncertain significance (May 18, 2022)
12-49543470-G-A		not specified	Uncertain significance (Jun 11, 2021)
12-49544030-A-G			Benign (Apr 15, 2020)
12-49544261-C-T			Benign (Jun 27, 2018)
12-49544262-G-A		not specified	Uncertain significance (Aug 02, 2021)
12-49544266-T-C		not specified	Uncertain significance (Dec 19, 2022)
12-49544303-C-T			Benign (Jul 16, 2018)
12-49544322-G-A		not specified	Likely benign (Oct 12, 2021)
12-49544344-G-A		not specified	Likely benign (Jun 28, 2023)
12-49544361-G-A		not specified	Uncertain significance (Jul 12, 2023)
12-49544380-T-C		not specified	Uncertain significance (Nov 12, 2021)
12-49548927-A-T		not specified	Uncertain significance (Jul 11, 2022)
12-49548942-G-C		not specified	Uncertain significance (Feb 27, 2024)
12-49548961-G-C		not specified	Uncertain significance (Oct 03, 2022)
12-49549000-G-A		not specified	Uncertain significance (Jun 02, 2023)
12-49549621-A-G		not specified	Uncertain significance (Jul 12, 2023)
12-49550209-C-T		not specified	Uncertain significance (Jan 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNH3	protein_coding	protein_coding	ENST00000257981	15	19152

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000813	125727	0	17	125744	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.85	403	687	0.587	0.0000427	6851
Missense in Polyphen		60	233	0.25751		2412
Synonymous	0.694	291	306	0.950	0.0000196	2403
Loss of Function	5.34	5	42.6	0.117	0.00000223	447

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000158	0.000139
European (Non-Finnish)	0.0000718	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.0000699	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

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

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.0322
• rvis_EVS: -0.88
• rvis_percentile_EVS: 10.56

Haploinsufficiency Scores

• pHI: 0.306
• hipred: Y
• hipred_score: 0.715
• ghis: 0.587

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.287

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnh3
• Phenotype: homeostasis/metabolism 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); vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: potassium ion transport;regulation of ion transmembrane transport;regulation of membrane potential;potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane
• Molecular function: voltage-gated potassium channel activity;protein binding