KCNH1

potassium voltage-gated channel subfamily H member 1, the group of Potassium voltage-gated channels|PAS domain containing

Basic information

Region (hg38): 1:210676822-211134165

Links

ENSG00000143473 ∙ NCBI:3756 ∙ OMIM:603305 ∙ HGNC:6250 ∙ Uniprot:O95259 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Temple-Baraitser syndrome (Strong), mode of inheritance: AD
• Temple-Baraitser syndrome (Moderate), mode of inheritance: AD
• Zimmermann-Laband syndrome 1 (Moderate), mode of inheritance: AD
• Zimmermann-Laband syndrome (Supportive), mode of inheritance: AR
• Temple-Baraitser syndrome (Supportive), mode of inheritance: AD
• KCNH1 associated disorder (Strong), mode of inheritance: AD
• Temple-Baraitser syndrome (Strong), mode of inheritance: AD
• KCNH1 associated disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Temple-Baraitser syndrome; Zimmermann-Laband syndrome 1	AD/AR	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	Craniofacial; Dental; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic	18203178; 20683999; 23994350; 24357613; 25420144; 25915598

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNH1 gene.

• not provided (529 variants)
• Inborn genetic diseases (23 variants)
• Zimmermann-Laband syndrome 1 (13 variants)
• Temple-Baraitser syndrome (12 variants)
• KCNH1-related condition (7 variants)
• Zimmermann-Laband syndrome 1;Temple-Baraitser syndrome (5 variants)
• not specified (5 variants)
• Temple-Baraitser syndrome;Zimmermann-Laband syndrome 1 (4 variants)
• See cases (3 variants)
• KCNH1 associated disorder (2 variants)
• Developmental disorder (2 variants)
• KCNH1-related disorders (2 variants)
• Abnormal facial shape;Intellectual disability, severe;Seizure (1 variants)
• Neurodevelopmental disorder (1 variants)
• KCNH1-related phenotype (1 variants)
• Seizure (1 variants)
• KCNH1-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNH1 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	139	12	153
missense	7	12	185	34	25	263
nonsense			3	1		4
start loss						0
frameshift			7	2		9
inframe indel			1			1
splice donor/acceptor (+/-2bp)			3			3
splice region			3	16	7	26
non coding				56	34	90
Total	7	12	201	232	71

Variants in KCNH1

This is a list of pathogenic ClinVar variants found in the KCNH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-210683243-G-T			Benign (Jul 15, 2018)
1-210683262-T-G			Benign (Jul 17, 2018)
1-210683275-G-A			Benign (Jul 03, 2019)
1-210683284-G-A			Likely benign (Oct 15, 2023)
1-210683284-G-C			Uncertain significance (Dec 09, 2023)
1-210683288-G-C			Benign (Dec 19, 2022)
1-210683289-C-A		KCNH1-related disorder	Benign/Likely benign (Oct 09, 2023)
1-210683294-A-G			Uncertain significance (Jun 22, 2021)
1-210683299-G-C			Uncertain significance (Oct 17, 2023)
1-210683299-GTCTC-G			Likely benign (Aug 15, 2022)
1-210683301-C-G			Uncertain significance (Dec 18, 2023)
1-210683304-T-C			Uncertain significance (Jun 14, 2023)
1-210683309-G-A			Uncertain significance (Nov 27, 2023)
1-210683309-G-C		not specified	Likely benign (Dec 08, 2023)
1-210683309-G-T			Uncertain significance (Jan 07, 2022)
1-210683310-A-C		Intellectual disability	Likely benign (Jan 01, 2019)
1-210683316-G-A			Uncertain significance (Jan 17, 2023)
1-210683321-T-C			Uncertain significance (Jan 24, 2024)
1-210683323-T-C			Likely benign (Jun 14, 2023)
1-210683323-T-G			Likely benign (Jan 10, 2024)
1-210683324-G-A			Uncertain significance (Jan 15, 2023)
1-210683329-C-T			Likely benign (Feb 20, 2022)
1-210683330-G-A			Likely benign (Sep 29, 2023)
1-210683339-A-C			Uncertain significance (Jun 13, 2022)
1-210683340-A-G			Benign (Feb 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNH1	protein_coding	protein_coding	ENST00000271751	11	450903

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.546	0.454	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.82	317	574	0.552	0.0000333	6524
Missense in Polyphen		50	179.06	0.27923		2042
Synonymous	0.143	229	232	0.988	0.0000144	1958
Loss of Function	4.45	8	37.3	0.214	0.00000193	432

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000217	0.000163
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.000217	0.000163
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:9738473, PubMed:11943152, PubMed:10880439, PubMed:22732247, PubMed:25556795, PubMed:27325704, PubMed:27005320, PubMed:27618660). Channel properties are modulated by subunit assembly (PubMed:11943152). Mediates IK(NI) current in myoblasts (PubMed:9738473). Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (PubMed:23881642). {ECO:0000269|PubMed:10880439, ECO:0000269|PubMed:11943152, ECO:0000269|PubMed:22732247, ECO:0000269|PubMed:23881642, ECO:0000269|PubMed:25556795, ECO:0000269|PubMed:27005320, ECO:0000269|PubMed:27325704, ECO:0000269|PubMed:27618660, ECO:0000269|PubMed:9738473}.
• Disease: DISEASE: Temple-Baraitser syndrome (TMBTS) [MIM:611816]: A developmental disorder characterized by intellectual disability, epilepsy, hypoplasia or aplasia of the thumb and great toe nails, and broadening and/or elongation of the thumbs and halluces, which have a tubular aspect. Some patients show facial dysmorphism. {ECO:0000269|PubMed:25420144}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Zimmermann-Laband syndrome 1 (ZLS1) [MIM:135500]: A disorder characterized by gingival fibromatosis, dysplastic or absent nails, finger abnormalities, hepatosplenomegaly, and abnormalities of the cartilage of the nose and/or ears. {ECO:0000269|PubMed:25915598}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.215

Intolerance Scores

• loftool: 0.0368
• rvis_EVS: -1.09
• rvis_percentile_EVS: 7.15

Haploinsufficiency Scores

• pHI: 0.507
• hipred: Y
• hipred_score: 0.784
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.849

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnh1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: kcnh1b
• Affected structure: somite border
• Phenotype tag: abnormal
• Phenotype quality: inconspicuous

Gene ontology

• Biological process: startle response;potassium ion transport;myoblast fusion;regulation of ion transmembrane transport;regulation of cell population proliferation;regulation of membrane potential;phosphatidylinositol-mediated signaling;cellular response to calcium ion;potassium ion transmembrane transport
• Cellular component: nuclear inner membrane;plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;cell surface;postsynaptic density;cell junction;dendrite;axolemma;early endosome membrane;perikaryon;intracellular membrane-bounded organelle;postsynaptic membrane;perinuclear region of cytoplasm;integral component of presynaptic membrane
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;calmodulin binding;protein kinase binding;cyclic nucleotide binding;identical protein binding;ion channel binding;protein heterodimerization activity;14-3-3 protein binding;phosphatidylinositol bisphosphate binding