• Gene id: 10021

Gene Summary

• Gene Symbol: HCN4   Gene   UCSC   Ensembl
• Aliases: SSS2
• Gene name: hyperpolarization activated cyclic nucleotide gated potassium channel 4
• Alternate names: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4, hyperpolarization activated cyclic nucleotide-gated cation channel 4,
• Gene location: 15q24.1 (73368957: 73319858)     Exons: 9     NC_000015.10
• Gene summary(Entrez): This gene encodes a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also me
• OMIM: 603006

Protein Summary

• Protein general information: Q9Y3Q4  
  • Name: Potassium/sodium hyperpolarization activated cyclic nucleotide gated channel 4
  • Length: 1203  
  • Mass: 129042
  • Tissue specificity: Highly expressed in thalamus, testis and in heart, both in ventricle and atrium. Detected at much lower levels in amygdala, substantia nigra, cerebellum and hippocampus. {ECO
• Sequence:

  MDKLPPSMRKRLYSLPQQVGAKAWIMDEEEDAEEEGAGGRQDPSRRSIRLRPLPSPSPSAAAGGTESRSSALGAA
  DSEGPARGAGKSSTNGDCRRFRGSLASLGSRGGGSGGTGSGSSHGHLHDSAEERRLIAEGDASPGEDRTPPGLAA
  EPERPGASAQPAASPPPPQQPPQPASASCEQPSVDTAIKVEGGAAAGDQILPEAEVRLGQAGFMQRQFGAMLQPG
  VNKFSLRMFGSQKAVEREQERVKSAGFWIIHPYSDFRFYWDLTMLLLMVGNLIIIPVGITFFKDENTTPWIVFNV
  VSDTFFLIDLVLNFRTGIVVEDNTEIILDPQRIKMKYLKSWFMVDFISSIPVDYIFLIVETRIDSEVYKTARALR
  IVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDLASAVVRIVNLIGMMLLLCHWDGCLQFLVPMLQDFPDDCW
  VSINNMVNNSWGKQYSYALFKAMSHMLCIGYGRQAPVGMSDVWLTMLSMIVGATCYAMFIGHATALIQSLDSSRR
  QYQEKYKQVEQYMSFHKLPPDTRQRIHDYYEHRYQGKMFDEESILGELSEPLREEIINFNCRKLVASMPLFANAD
  PNFVTSMLTKLRFEVFQPGDYIIREGTIGKKMYFIQHGVVSVLTKGNKETKLADGSYFGEICLLTRGRRTASVRA
  DTYCRLYSLSVDNFNEVLEEYPMMRRAFETVALDRLDRIGKKNSILLHKVQHDLNSGVFNYQENEIIQQIVQHDR
  EMAHCAHRVQAAASATPTPTPVIWTPLIQAPLQAAAATTSVAIALTHHPRLPAAIFRPPPGSGLGNLGAGQTPRH
  LKRLQSLIPSALGSASPASSPSQVDTPSSSSFHIQQLAGFSAPAGLSPLLPSSSSSPPPGACGSPSAPTPSAGVA
  ATTIAGFGHFHKALGGSLSSSDSPLLTPLQPGARSPQAAQPSPAPPGARGGLGLPEHFLPPPPSSRSPSSSPGQL
  GQPPGELSLGLATGPLSTPETPPRQPEPPSLVAGASGGASPVGFTPRGGLSPPGHSPGPPRTFPSAPPRASGSHG
  SLLLPPASSPPPPQVPQRRGTPPLTPGRLTQDLKLISASQPALPQDGAQTLRRASPHSSGESMAAFPLFPRAGGG
  SGGSGSSGGLGPPGRPYGAIPGQHVTLPRKTSSGSLPPPLSLFGARATSSGGPPLTAGPQREPGARPEPVRSKLP
  SNL

• Structural information:
  • Interpro: IPR018490  IPR018488  IPR000595  IPR030173  IPR005821   IPR013621  IPR003938  IPR014710  IPR027359  
  • Prosite: PS00888 PS50042
  • CDD: cd00038
  • PDB: 2MNG 3OTF 3U11 4HBN 4KL1 4NVP 6GYN 6GYO
  • PDBsum: 2MNG 3OTF 3U11 4HBN 4KL1 4NVP 6GYN 6GYO
  • DIP: 52325
  • STRING: ENSP00000261917
• Other Databases: GeneCards:  HCN4  Malacards:  HCN4

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0071320	cellular response to cAMP	IDA	biological process
GO:0071805	potassium ion transmembrane transport	IDA	biological process
GO:0031226	intrinsic component of plasma membrane	IDA	cellular component
GO:0005249	voltage-gated potassium channel activity	IDA	molecular function
GO:0005222	intracellular cAMP-activated cation channel activity	IDA	molecular function
GO:0002027	regulation of heart rate	IMP	biological process
GO:0006814	sodium ion transport	IEA	biological process
GO:0002027	regulation of heart rate	IEA	biological process
GO:0005216	ion channel activity	IEA	molecular function
GO:0005249	voltage-gated potassium channel activity	IEA	molecular function
GO:0006811	ion transport	IEA	biological process
GO:0006813	potassium ion transport	IEA	biological process
GO:0016020	membrane	IEA	cellular component
GO:0016021	integral component of membrane	IEA	cellular component
GO:0030552	cAMP binding	IEA	molecular function
GO:0055085	transmembrane transport	IEA	biological process
GO:0005272	sodium channel activity	IEA	molecular function
GO:0005267	potassium channel activity	IEA	molecular function
GO:0005244	voltage-gated ion channel activity	IEA	molecular function
GO:0006814	sodium ion transport	IEA	biological process
GO:0000166	nucleotide binding	IEA	molecular function
GO:0016020	membrane	IEA	cellular component
GO:0016021	integral component of membrane	IEA	cellular component
GO:0034765	regulation of ion transmembrane transport	IEA	biological process
GO:0006813	potassium ion transport	IEA	biological process
GO:0030552	cAMP binding	IEA	molecular function
GO:0071805	potassium ion transmembrane transport	IEA	biological process
GO:0006811	ion transport	IEA	biological process
GO:0005886	plasma membrane	IEA	cellular component
GO:0006936	muscle contraction	TAS	biological process
GO:0008015	blood circulation	NAS	biological process
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0042802	identical protein binding	IPI	molecular function
GO:0042802	identical protein binding	IPI	molecular function
GO:0005222	intracellular cAMP-activated cation channel activity	IDA	molecular function
GO:0005222	intracellular cAMP-activated cation channel activity	IDA	molecular function
GO:0086041	voltage-gated potassium channel activity involved in SA node cell action potential depolarization	IMP	molecular function
GO:0006812	cation transport	IDA	biological process
GO:0071320	cellular response to cAMP	IDA	biological process
GO:0048471	perinuclear region of cytoplasm	IDA	cellular component
GO:0098855	HCN channel complex	IDA	cellular component
GO:0098855	HCN channel complex	IDA	cellular component
GO:0098719	sodium ion import across plasma membrane	IDA	biological process
GO:0086012	membrane depolarization during cardiac muscle cell action potential	IC	biological process
GO:0055117	regulation of cardiac muscle contraction	IMP	biological process
GO:0003254	regulation of membrane depolarization	IDA	biological process
GO:0005886	plasma membrane	IDA	cellular component
GO:1990573	potassium ion import across plasma membrane	IDA	biological process
GO:0098909	regulation of cardiac muscle cell action potential involved in regulation of contraction	IMP	biological process
GO:0086015	SA node cell action potential	IMP	biological process
GO:0086091	regulation of heart rate by cardiac conduction	IMP	biological process
GO:0086046	membrane depolarization during SA node cell action potential	IMP	biological process
GO:0005886	plasma membrane	IEA	cellular component
GO:0071321	cellular response to cGMP	IDA	biological process
GO:0005886	plasma membrane	IDA	cellular component
GO:0071320	cellular response to cAMP	IDA	biological process
GO:0071805	potassium ion transmembrane transport	IMP	biological process
GO:0042391	regulation of membrane potential	IMP	biological process
GO:0005249	voltage-gated potassium channel activity	IMP	molecular function
GO:0035725	sodium ion transmembrane transport	IMP	biological process
GO:0005248	voltage-gated sodium channel activity	IMP	molecular function

KEGG pathways

Pathway id	Pathway name
hsa04024	cAMP signaling pathway
hsa04742	Taste transduction

Diseases

Associated diseases	References
Brugada syndrome	KEGG:H00728
Sick sinus syndrome	KEGG:H00729
Brugada syndrome	KEGG:H00728
Sick sinus syndrome	KEGG:H00729
Gilles de la Tourette syndrome	PMID:22683190
Cryptorchidism	MIK: 28606200

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq