GeneBe

KCNH1

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

Basic information

Region (hg38): 1:210676823-211134165

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Temple-Baraitser syndrome; Zimmermann-Laband syndrome 1AD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Dental; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic18203178; 20683999; 23994350; 24357613; 25420144; 25915598

ClinVar

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

  • not_provided (727 variants)
  • Inborn_genetic_diseases (62 variants)
  • KCNH1-related_disorder (37 variants)
  • Zimmermann-Laband_syndrome_1 (28 variants)
  • Temple-Baraitser_syndrome (28 variants)
  • not_specified (14 variants)
  • KCNH1_associated_disorder (3 variants)
  • Intellectual_disability (3 variants)
  • See_cases (3 variants)
  • Developmental_disorder (2 variants)
  • Neurodevelopmental_disorder (1 variants)
  • KCNH1-related_phenotype (1 variants)
  • Epilepsy (1 variants)
  • KCNH1-related_neurodevelopmental_disorder_with_multiple_anomalies (1 variants)
  • Intellectual_disability,_severe (1 variants)
  • Abnormal_facial_shape (1 variants)
  • Seizure (1 variants)
  • Neurodevelopmental_abnormality (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. These statistics are base on transcript: NM_000172362.3. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
201
clinvar
9
clinvar
 212
missense
14
clinvar
16
clinvar
315
clinvar
78
clinvar
18
clinvar
 441
nonsense
6
clinvar
1
clinvar
 7
start loss
0
frameshift
11
clinvar
2
clinvar
 13
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total 14 16 337 282 27

Highest pathogenic variant AF is 0.0000041340477

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KCNH1protein_codingprotein_codingENST00000271751 11450903
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.5460.4541257230251257480.0000994
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.823175740.5520.00003336524
Missense in Polyphen50179.060.279232042
Synonymous0.1432292320.9880.00001441958
Loss of Function4.45837.30.2140.00000193432

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002100.000210
Ashkenazi Jewish0.00009930.0000992
East Asian0.0002170.000163
Finnish0.00004630.0000462
European (Non-Finnish)0.0001070.000105
Middle Eastern0.0002170.000163
South Asian0.00009810.0000980
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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