Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene miRNA Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	610
Gene name	Hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2
Gene symbol	HCN2
Synonyms (NCBI Gene)	BCNG-2BCNG2EIG17FEB2GEFSP11HAC-1
Chromosome	19
Chromosome location	19p13.3
Summary	The protein encoded by this gene is a hyperpolarization-activated cation channel involved in the generation of native pacemaker activity in the heart and in the brain. The encoded protein is activated by cAMP and can produce a fast, large current. Defects

Show/Hide all (78)

miRTarBase ID	miRNA	Experiments	Reference
MIRT001205	hsa-miR-1-3p	Luciferase reporter assayWestern blot	19136465
MIRT001204	hsa-miR-133a-3p	Luciferase reporter assayWestern blot	19136465
MIRT001205	hsa-miR-1-3p	qRT-PCRLuciferase reporter assayWestern blot	18458081
MIRT001204	hsa-miR-133a-3p	qRT-PCRLuciferase reporter assayWestern blot	18458081
MIRT001204	hsa-miR-133a-3p	Luciferase reporter assay	18458081
MIRT016693	hsa-miR-133b	Reporter assay	18458081
MIRT023091	hsa-miR-124-3p	Microarray	18668037
MIRT001205	hsa-miR-1-3p	Reporter assay;Western blot;qRT-PCR	18458081
MIRT491253	hsa-miR-3943	PAR-CLIP	23592263
MIRT491252	hsa-miR-6795-3p	PAR-CLIP	23592263
MIRT491251	hsa-miR-6803-3p	PAR-CLIP	23592263
MIRT491249	hsa-miR-7515	PAR-CLIP	23592263
MIRT491250	hsa-miR-3179	PAR-CLIP	23592263
MIRT491248	hsa-miR-1225-3p	PAR-CLIP	23592263
MIRT491247	hsa-miR-4313	PAR-CLIP	23592263
MIRT491246	hsa-miR-6827-5p	PAR-CLIP	23592263
MIRT491245	hsa-miR-6864-5p	PAR-CLIP	23592263
MIRT491253	hsa-miR-3943	PAR-CLIP	23592263
MIRT491252	hsa-miR-6795-3p	PAR-CLIP	23592263
MIRT491251	hsa-miR-6803-3p	PAR-CLIP	23592263
MIRT491249	hsa-miR-7515	PAR-CLIP	23592263
MIRT491250	hsa-miR-3179	PAR-CLIP	23592263
MIRT491248	hsa-miR-1225-3p	PAR-CLIP	23592263
MIRT491247	hsa-miR-4313	PAR-CLIP	23592263
MIRT491246	hsa-miR-6827-5p	PAR-CLIP	23592263
MIRT491245	hsa-miR-6864-5p	PAR-CLIP	23592263
MIRT1042107	hsa-miR-1207-3p	CLIP-seq
MIRT1042108	hsa-miR-1247	CLIP-seq
MIRT1042109	hsa-miR-1275	CLIP-seq
MIRT1042110	hsa-miR-1291	CLIP-seq
MIRT1042111	hsa-miR-1827	CLIP-seq
MIRT1042112	hsa-miR-1913	CLIP-seq
MIRT1042113	hsa-miR-25	CLIP-seq
MIRT1042114	hsa-miR-3173-5p	CLIP-seq
MIRT1042115	hsa-miR-3191	CLIP-seq
MIRT1042116	hsa-miR-32	CLIP-seq
MIRT1042117	hsa-miR-324-3p	CLIP-seq
MIRT1042118	hsa-miR-363	CLIP-seq
MIRT1042119	hsa-miR-367	CLIP-seq
MIRT1042120	hsa-miR-3917	CLIP-seq
MIRT1042121	hsa-miR-4325	CLIP-seq
MIRT1042122	hsa-miR-4471	CLIP-seq
MIRT1042123	hsa-miR-4480	CLIP-seq
MIRT1042124	hsa-miR-4525	CLIP-seq
MIRT1042125	hsa-miR-4649-3p	CLIP-seq
MIRT1042126	hsa-miR-4665-5p	CLIP-seq
MIRT1042127	hsa-miR-4723-5p	CLIP-seq
MIRT1042128	hsa-miR-4731-5p	CLIP-seq
MIRT1042129	hsa-miR-548ad	CLIP-seq
MIRT1042130	hsa-miR-600	CLIP-seq
MIRT1042131	hsa-miR-625	CLIP-seq
MIRT1042132	hsa-miR-637	CLIP-seq
MIRT1042133	hsa-miR-671-5p	CLIP-seq
MIRT1042134	hsa-miR-92a	CLIP-seq
MIRT1042135	hsa-miR-92b	CLIP-seq
MIRT1042108	hsa-miR-1247	CLIP-seq
MIRT2008849	hsa-miR-1285	CLIP-seq
MIRT2008850	hsa-miR-135a	CLIP-seq
MIRT2008851	hsa-miR-135b	CLIP-seq
MIRT2008852	hsa-miR-137	CLIP-seq
MIRT2008853	hsa-miR-3187-5p	CLIP-seq
MIRT2008854	hsa-miR-378g	CLIP-seq
MIRT2008855	hsa-miR-4314	CLIP-seq
MIRT2008856	hsa-miR-4467	CLIP-seq
MIRT2008857	hsa-miR-4486	CLIP-seq
MIRT2008858	hsa-miR-4515	CLIP-seq
MIRT2008859	hsa-miR-612	CLIP-seq
MIRT2008860	hsa-miR-885-3p	CLIP-seq
MIRT2008849	hsa-miR-1285	CLIP-seq
MIRT2008850	hsa-miR-135a	CLIP-seq
MIRT2008851	hsa-miR-135b	CLIP-seq
MIRT2008853	hsa-miR-3187-5p	CLIP-seq
MIRT2008854	hsa-miR-378g	CLIP-seq
MIRT2008855	hsa-miR-4314	CLIP-seq
MIRT2008856	hsa-miR-4467	CLIP-seq
MIRT2008857	hsa-miR-4486	CLIP-seq
MIRT2008858	hsa-miR-4515	CLIP-seq
MIRT2008859	hsa-miR-612	CLIP-seq

Show/Hide all (1)

Transcription factor	Regulation	Reference
SP1	Activation	19471099

Show/Hide all (59)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003254	Process	Regulation of membrane depolarization	IBA
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005222	Function	Intracellularly cAMP-activated cation channel activity	IDA	10228147
GO:0005248	Function	Voltage-gated sodium channel activity	IMP	22748890
GO:0005249	Function	Voltage-gated potassium channel activity	IBA
GO:0005249	Function	Voltage-gated potassium channel activity	IDA	10228147
GO:0005249	Function	Voltage-gated potassium channel activity	IEA
GO:0005249	Function	Voltage-gated potassium channel activity	IMP	22748890
GO:0005267	Function	Potassium channel activity	IEA
GO:0005272	Function	Sodium channel activity	IEA
GO:0005515	Function	Protein binding	IPI	26966193
GO:0005886	Component	Plasma membrane	IDA	10228147, 22748890
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006813	Process	Potassium ion transport	IEA
GO:0006814	Process	Sodium ion transport	IEA
GO:0007267	Process	Cell-cell signaling	TAS	9630217
GO:0008076	Component	Voltage-gated potassium channel complex	TAS	9630217
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0009725	Process	Response to hormone	IEA
GO:0016020	Component	Membrane	IEA
GO:0030165	Function	PDZ domain binding	IEA
GO:0030424	Component	Axon	IBA
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IBA
GO:0030552	Function	CAMP binding	IEA
GO:0032590	Component	Dendrite membrane	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034702	Component	Monoatomic ion channel complex	IEA
GO:0035725	Process	Sodium ion transmembrane transport	IBA
GO:0035725	Process	Sodium ion transmembrane transport	IMP	22748890
GO:0036477	Component	Somatodendritic compartment	IEA
GO:0042391	Process	Regulation of membrane potential	IEA
GO:0042391	Process	Regulation of membrane potential	IMP	22748890
GO:0042802	Function	Identical protein binding	IPI	22006928
GO:0043025	Component	Neuronal cell body	IEA
GO:0043198	Component	Dendritic shaft	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0060090	Function	Molecular adaptor activity	IEA
GO:0071320	Process	Cellular response to cAMP	IDA	10228147, 22748890
GO:0071320	Process	Cellular response to cAMP	IEA
GO:0071321	Process	Cellular response to cGMP	IDA	22748890
GO:0071805	Process	Potassium ion transmembrane transport	IBA
GO:0071805	Process	Potassium ion transmembrane transport	IDA	10228147
GO:0071805	Process	Potassium ion transmembrane transport	IEA
GO:0071805	Process	Potassium ion transmembrane transport	IMP	22748890
GO:0072488	Process	Ammonium transmembrane transport	IEA
GO:0072488	Process	Ammonium transmembrane transport	ISS
GO:0086012	Process	Membrane depolarization during cardiac muscle cell action potential	IC	10228147
GO:0098719	Process	Sodium ion import across plasma membrane	IDA	10228147
GO:0098719	Process	Sodium ion import across plasma membrane	IEA
GO:0098855	Component	HCN channel complex	IBA
GO:0098855	Component	HCN channel complex	IDA	10228147
GO:0098855	Component	HCN channel complex	IEA
GO:1904045	Process	Cellular response to aldosterone	IEA
GO:1990573	Process	Potassium ion import across plasma membrane	IDA	10228147

MIM	HGNC	e!Ensembl
602781	4846	ENSG00000099822

Q9UL51

Protein name

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (Brain cyclic nucleotide-gated channel 2) (BCNG-2)

Protein function

Hyperpolarization-activated ion channel that is permeable to sodium and potassium ions. Displays lower selectivity for K(+) over Na(+) ions (PubMed:10228147, PubMed:22006928). Contributes to the native pacemaker currents in heart (If) and in neu

PDB

2MPF , 3U10

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF08412	Ion_trans_N	167 → 210	Ion transport protein N-terminal	Family
PF00520	Ion_trans	211 → 474	Ion transport protein	Family
PF00027	cNMP_binding	562 → 645	Cyclic nucleotide-binding domain	Domain

Tissue specificity

TISSUE SPECIFICITY: Highly expressed throughout the brain. Detected at low levels in heart. {ECO:0000269|PubMed:10228147, ECO:0000269|PubMed:9630217}.

Sequence

MDARGGGGRPGESPGATPAPGPPPPPPPAPPQQQPPPPPPPAPPPGPGPAPPQHPPRAEA
LPPEAADEGGPRGRLRSRDSSCGRPGTPGAASTAKGSPNGECGRGEPQCSPAGPEGPARG
PKVSFSCRGAASGPAPGPGPAEEAGSEEAGPAGEPRGSQASFMQRQFGALLQPGVNKFSL
RMFGSQKAVEREQERVKSAGAWIIHPYSDFRFYWDFTMLLFMVGNLIIIPVGITFFKDET
TAPWIVFNVVSDTFFLMDLVLNFRTGIVIEDNTEIILDPEKIKKKYLRTWFVVDFVSSIP
VDYIFLIVEKGIDSEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDL
ASAVMRICNLISMMLLLCHWDGCLQFLVPMLQDFPRNCWVSINGMVNHSWSELYSFALFK
AMSHMLCIGYGRQAPESMTDIWLTMLSMIVGATCYAMFIGHATALIQSLDSSRRQYQEKY
KQVEQYMSFHKLPADFRQKIHDYYEHRYQGKMFDEDSILGELNGPLREEIVNFNCRKLVA
SMPLFANADPNFVTAMLTKLKFEVFQPGDYIIREGTIGKKMYFIQHGVVSVLTKGNKEMK
LSDGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEVLEEYPMMRRAFETVAIDRL
DRIGKKNSILLHKVQHDLNSGVFNNQENAIIQEIVKYDREMVQQAELGQRVGLFPPPPPP
PQVTSAIATLQQAAAMSFCPQVARPLVGPLALGSPRLVRRPPPGPAPAAASPGPPPPASP
PGAPASPRAPRTSPYGGLPAAPLAGPALPARRLSRASRPLSASQPSLPHGAPGPAASTRP
ASSSTPRLGPTPAARAAAPSPDRRDSASPGAAGGLDPQDSARSRLSSNL

Sequence length

889

Interactions

View interactions

	KEGG		Reactome
	cAMP signaling pathway GnRH secretion		HCN channels

Show/Hide Causal Diseases (4)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Epilepsy, idiopathic generalized, susceptibility to, 17	Likely pathogenic; Pathogenic	rs1983378020	RCV003992484
Febrile seizures, familial, 2	Pathogenic	rs1258293482	RCV001637971
HCN2 related developmental and epileptic encephalopathy	Likely pathogenic; Pathogenic	rs2144522815, rs2512439870, rs2512449193, rs2512450547, rs756318406, rs2512454602, rs746133376, rs2512459304, rs2512452816, rs1983378020	RCV003772053 RCV003223347 RCV003223348 RCV003223349 RCV003223350 RCV003223351 RCV003223352 RCV003223353 RCV003881671 RCV003770369
Neurodevelopmental delay	Likely pathogenic; Pathogenic	rs2144522815	RCV003223427

Show/Hide Unknown Diseases (20)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Acute myeloid leukemia	Likely benign	rs55978915	RCV005898267
Cardiomyopathy	Uncertain significance	rs1172334880	RCV003448935
Cervical cancer	Likely benign	rs55978915	RCV005898269
Cholangiocarcinoma	Benign	rs34104611	RCV005914818
Febrile seizure (within the age range of 3 months to 6 years)	not provided	rs2144522700	RCV001825234
Gastric cancer	Likely benign	rs55978915	RCV005898272
Generalized epilepsy	not provided	rs2144522700	RCV001825234
HCN2-associated Epilepsy syndrome	Uncertain significance	rs1983900447	RCV002227810
HCN2-related disorder	Uncertain significance; Likely benign; Benign	rs1483818563, rs778645411, rs746420784, rs146953957, rs148730222, rs2512448958, rs1228076288, rs150388404, rs147575578, rs200053654, rs200925272, rs371009589, rs145767637, rs563181576, rs80135478, rs55978915, rs3752158 View all (2 more)	RCV004753649 RCV003391405 RCV003402392 RCV003929097 RCV003898915 RCV003896281 RCV003912077 RCV003943964 RCV003931521 RCV003941654 RCV003949780 RCV003934745 RCV003926765 RCV003936790 RCV003964346 RCV003970261 RCV004753133
Lung cancer	Likely benign	rs55978915	RCV005898276
Malignant lymphoma, large B-cell, diffuse	Benign	rs34104611	RCV005914816
Malignant tumor of esophagus	Likely benign	rs55978915	RCV005898268
Ovarian serous cystadenocarcinoma	Likely benign	rs55978915	RCV005898273
Sarcoma	Likely benign	rs55978915	RCV005898271
See cases	Conflicting classifications of pathogenicity	rs750959680	RCV001542410
Seizure	Uncertain significance	rs2144522788	RCV002275909
Thymoma	Likely benign	rs55978915	RCV005898275
Uterine carcinosarcoma	Benign; Likely benign	rs34104611, rs55978915	RCV005914817 RCV005898274
Uterine corpus endometrial carcinoma	Likely benign	rs55978915	RCV005898277
Uveal melanoma	Likely benign	rs55978915	RCV005898270

Show/Hide Text Mining Associations (17)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Acute Coronary Syndrome	Associate	28666417
Atrial Fibrillation	Associate	21179275
Atrial Fibrillation	Stimulate	26005035
Brain Ischemia	Associate	32519067
Breast Neoplasms	Stimulate	34841695
Cardiac Complexes Premature	Associate	26005035
Coronary Artery Disease	Associate	28666417
Edema	Associate	37298834
Encephalitis	Associate	7700510
Heart Diseases	Associate	24427266
Heart Valve Diseases	Associate	21179275
Hirschsprung Disease	Associate	25987789
Ileus	Associate	37298834
Ischemic Attack Transient	Associate	32519067
Myocardial Ischemia	Associate	32519067
Osteoglophonic dwarfism	Associate	32519067
Sudden Unexpected Death in Epilepsy	Associate	21615589

HCN2 (hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2)