HCN1
hyperpolarization activated cyclic nucleotide gated potassium channel 1, the group of Cyclic nucleotide gated channels
Basic information
Region (hg38): 5:45254948-45696498
Previous symbols: [ "BCNG1" ]
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy, 24 (Definitive), mode of inheritance: AD
- developmental and epileptic encephalopathy, 24 (Definitive), mode of inheritance: AD
- generalized epilepsy with febrile seizures plus (Supportive), mode of inheritance: AD
- undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
- developmental and epileptic encephalopathy, 24 (Strong), mode of inheritance: AD
- generalized epilepsy with febrile seizures plus, type 10 (Strong), mode of inheritance: AD
- generalized epilepsy with febrile seizures plus (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Developmental and epileptic encephalopathy 24; Generalized epilepsy with febrile seizures plus, type 10 | 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 | 24747641; 29936235; 30351409 |
| 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
- Developmental_and_epileptic_encephalopathy (778 variants)
- not_provided (261 variants)
- Inborn_genetic_diseases (135 variants)
- Developmental_and_epileptic_encephalopathy,_24 (47 variants)
- Generalized_epilepsy_with_febrile_seizures_plus,_type_10 (39 variants)
- HCN1-related_disorder (26 variants)
- not_specified (24 variants)
- Intellectual_disability (5 variants)
- Seizure (4 variants)
- Epileptic_encephalopathy (2 variants)
- Color_vision_defect (1 variants)
- Febrile_seizure_(within_the_age_range_of_3_months_to_6_years) (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 HCN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021072.4. 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 | 272 | 282 | ||||
| missense | 19 | 27 | 433 | 82 | 562 | |
| nonsense | 14 | 15 | ||||
| start loss | 3 | 3 | ||||
| frameshift | 22 | 24 | ||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| Total | 19 | 29 | 483 | 355 | 6 |
Highest pathogenic variant AF is 0.0000446218
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HCN1 | protein_coding | protein_coding | ENST00000303230 | 8 | 436905 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000108 | 125743 | 0 | 5 | 125748 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.66 | 261 | 489 | 0.534 | 0.0000278 | 5792 |
| Missense in Polyphen | 80 | 216.2 | 0.37002 | 2516 | ||
| Synonymous | -2.32 | 242 | 200 | 1.21 | 0.0000130 | 1801 |
| Loss of Function | 5.15 | 2 | 34.8 | 0.0575 | 0.00000196 | 377 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000443 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions (PubMed:28086084). Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli. {ECO:0000269|PubMed:15351778, ECO:0000269|PubMed:28086084}.;
- Disease
- DISEASE: Epileptic encephalopathy, early infantile, 24 (EIEE24) [MIM:615871]: A disease characterized by early-onset seizures, intellectual disability of varying degrees, and behavioral disturbances or autistic features in most individuals. {ECO:0000269|PubMed:24747641, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Neuronal System;HCN channels;Potassium Channels
(Consensus)
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- loftool
- 0.111
- rvis_EVS
- -0.76
- rvis_percentile_EVS
- 13.33
Haploinsufficiency Scores
- pHI
- 0.581
- hipred
- Y
- hipred_score
- 0.806
- ghis
- 0.658
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hcn1
- Phenotype
- normal 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system 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); craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; taste/olfaction phenotype;
Gene ontology
- Biological process
- regulation of ion transmembrane transport;sodium ion transmembrane transport;regulation of membrane potential;apical protein localization;retinal cone cell development;protein homotetramerization;cellular response to cAMP;potassium ion transmembrane transport
- Cellular component
- plasma membrane;integral component of plasma membrane;axon;dendrite;HCN channel complex
- Molecular function
- intracellular cAMP-activated cation channel activity;voltage-gated sodium channel activity;voltage-gated potassium channel activity;potassium channel activity;protein binding;voltage-gated cation channel activity;cAMP binding;identical protein binding