Gene
hcn4
- ID
- ZDB-GENE-050420-360
- Name
- hyperpolarization activated cyclic nucleotide-gated potassium channel 4
- Symbol
- hcn4 Nomenclature History
- Previous Names
-
- si:ch211-203b17.1
- Type
- protein_coding_gene
- Location
- Chr: 18 Mapping Details/Browsers
- Description
- Predicted to enable voltage-gated potassium channel activity. Acts upstream of or within heart contraction. Predicted to be located in plasma membrane. Predicted to be part of HCN channel complex. Predicted to be active in axon and dendrite. Is expressed in cardiovascular system. Used to study sick sinus syndrome. Human ortholog(s) of this gene implicated in Brugada syndrome 8; Gilles de la Tourette syndrome; generalized epilepsy; and sick sinus syndrome. Orthologous to human HCN4 (hyperpolarization activated cyclic nucleotide gated potassium channel 4).
- Genome Resources
- Note
- None
- Comparative Information
-
- All Expression Data
- 10 figures from 9 publications
- Cross-Species Comparison
- High Throughput Data
- Thisse Expression Data
- No data available
Wild Type Expression Summary
Phenotype Summary
Mutations
| Allele | Type | Localization | Consequence | Mutagen | Supplier |
|---|---|---|---|---|---|
| nksaigff249ATg | Transgenic insertion | Exon 1 | Unknown | DNA | |
| sa11188 | Allele with one point mutation | Unknown | Premature Stop | ENU | |
| sa39186 | Allele with one point mutation | Unknown | Premature Stop | ENU |
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| Targeting Reagent | Created Alleles | Citations |
|---|---|---|
| CRISPR1-hcn4 | (2) | |
| CRISPR2-hcn4 | (2) | |
| CRISPR3-hcn4 | (2) | |
| CRISPR4-hcn4 | (2) | |
| CRISPR5-hcn4 | (2) | |
| CRISPR6-hcn4 | (2) | |
| CRISPR7-hcn4 | (2) | |
| CRISPR8-hcn4 | (2) | |
| CRISPR9-hcn4 | (2) | |
| CRISPR10-hcn4 | (2) |
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Human Disease
| Disease Ontology Term | Multi-Species Data | OMIM Term | OMIM Phenotype ID |
|---|---|---|---|
| Brugada syndrome 8 | Alliance | Brugada syndrome 8 | 613123 |
| sick sinus syndrome | Alliance | Sick sinus syndrome 2 | 163800 |
| {Epilepsy, idiopathic generalized, susceptibility to, 18} | 619521 |
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| Human Disease | Fish | Conditions | Citations |
|---|---|---|---|
| sick sinus syndrome | twu34Tg + MO1-hcn4 | standard conditions | Jou et al., 2017 |
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Domain, Family, and Site Summary
| Type | InterPro ID | Name |
|---|---|---|
| Conserved_site | IPR018488 | Cyclic nucleotide-binding, conserved site |
| Domain | IPR000595 | Cyclic nucleotide-binding domain |
| Domain | IPR005821 | Ion transport domain |
| Domain | IPR013621 | Ion transport N-terminal |
| Family | IPR003938 | Potassium channel, voltage-dependent, EAG/ELK/ERG-like |
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Domain Details Per Protein
| Protein | Additional Resources | Length | Cyclic nucleotide-binding, conserved site | Cyclic nucleotide-binding domain | Cyclic nucleotide-binding domain superfamily | Ion transport domain | Ion transport N-terminal | Potassium channel, voltage-dependent, EAG/ELK/ERG-like | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel | RmlC-like jelly roll fold |
|---|---|---|---|---|---|---|---|---|---|---|
| UniProtKB:A0A8N7UQR8 | InterPro | 1140 |
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Interactions and Pathways
No data available
Plasmids
No data available
No data available
| Relationship | Marker Type | Marker | Accession Numbers | Citations |
|---|---|---|---|---|
| Contained in | BAC | CH211-153O21 | ZFIN Curated Data | |
| Contained in | BAC | CH211-203B17 | ZFIN Curated Data |
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| Type | Accession # | Sequence | Length (nt/aa) | Analysis |
|---|---|---|---|---|
| RNA | RefSeq:XM_680986 (1) | 3886 nt | ||
| Genomic | GenBank:BX119923 (1) | 159232 nt | ||
| Polypeptide | UniProtKB:A0A8N7UQR8 (1) | 1140 aa |
- Jia, B.Z., Qi, Y., Wong-Campos, J.D., Megason, S.G., Cohen, A.E. (2023) A bioelectrical phase transition patterns the first vertebrate heartbeats. Nature. 622(7981):149-155
- Fang, C., Wang, P., Yu, D., Zhang, X., Gou, D., Liang, L., Bai, X., Xie, W., Li, H., Pu, J., Yao, Y., Wang, B., Ren, X., Ke, T., Tu, X., Xu, C., Wang, Q.K. (2022) Genome-Wide Association Study for Idiopathic Ventricular Tachyarrhythmias Identifies Key Role of CCR7 and PKN2 in Calcium Homeostasis and Cardiac Rhythm Maintenance. Circulation. Genomic and precision medicine. 15(5):e003603
- Höijer, I., Emmanouilidou, A., Östlund, R., van Schendel, R., Bozorgpana, S., Tijsterman, M., Feuk, L., Gyllensten, U., den Hoed, M., Ameur, A. (2022) CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations. Nature communications. 13:627
- Liu, J., Kasuya, G., Zempo, B., Nakajo, K. (2022) Two HCN4 Channels Play Functional Roles in the Zebrafish Heart. Frontiers in Physiology. 13:901571
- Kuo, M.W., Tsai, H.H., Wang, S.H., Chen, Y.Y., Yu, A.L., Yu, J. (2021) Yulink, predicted from evolutionary analysis, is involved in cardiac function. Journal of Biomedical Science. 28:7
- Fujii, K., Nakajo, K., Egashira, Y., Yamamoto, Y., Kitada, K., Taniguchi, K., Kawai, M., Tomiyama, H., Kawakami, K., Uchiyama, K., Ono, F. (2020) Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis. Cell Reports. 30:2879-2888.e3
- von der Heyde, B., Emmanouilidou, A., Mazzaferro, E., Vicenzi, S., Höijer, I., Klingström, T., Jumaa, S., Dethlefsen, O., Snieder, H., de Geus, E., Ameur, A., Ingelsson, E., Allalou, A., Brooke, H.L., den Hoed, M. (2020) Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9-based approach. Scientific Reports. 10:11831
- Burczyk, M.S., Burkhalter, M.D., Tena, T.C., Grisanti, L.A., Kauk, M., Matysik, S., Donow, C., Kustermann, M., Rothe, M., Cui, Y., Raad, F., Laue, S., Moretti, A., Zimmermann, W.H., Wess, J., Kühl, M., Hoffmann, C., Tilley, D.G., Philipp, M. (2019) Muscarinic receptors promote pacemaker fate at the expense of secondary conduction system tissue in zebrafish. JCI insight. 4(20):
- Collins, M.M., Ahlberg, G., Hansen, C.V., Guenther, S., Marín-Juez, R., Sokol, A.M., El-Sammak, H., Piesker, J., Hellsten, Y., Olesen, M.S., Stainier, D.Y.R., Lundegaard, P.R. (2019) Early sarcomere and metabolic defects in a zebrafish pitx2c cardiac arrhythmia model. Proceedings of the National Academy of Sciences of the United States of America. 116(48):24115-24121
- Ren, J., Han, P., Ma, X., Farah, E.N., Bloomekatz, J., Zeng, X.I., Zhang, R., Swim, M.M., Witty, A.D., Knight, H.G., Deshpande, R., Xu, W., Yelon, D., Chen, S., Chi, N.C. (2019) Canonical Wnt5b Signaling Directs Outlying Nkx2.5+ Mesoderm into Pacemaker Cardiomyocytes. Developmental Cell. 50(6):729-743.e5
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