Seroatlas · Human Serome Atlas

HCN2

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

Also known as: BCNG-2, BCNG2, HAC-1, HCN2_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q9UL51
Gene
HCN2
Ensembl
ENSG00000099822
Chromosome
19
Canonical length
889 aa
Protein class
Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters, Voltage-gated ion channels
Quaternary structure
Homotetramer

OverviewNCBI Gene

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 in this gene were noted as a possible cause of some forms of epilepsy. [provided by RefSeq, Jan 2017]

Canonical amino-acid sequenceUniProt

889 residues, UniProt reviewed canonical sequence.

>Q9UL51|HCN2
     1  MDARGGGGRP GESPGATPAP GPPPPPPPAP PQQQPPPPPP PAPPPGPGPA PPQHPPRAEA
    61  LPPEAADEGG PRGRLRSRDS SCGRPGTPGA ASTAKGSPNG ECGRGEPQCS PAGPEGPARG
   121  PKVSFSCRGA ASGPAPGPGP AEEAGSEEAG PAGEPRGSQA SFMQRQFGAL LQPGVNKFSL
   181  RMFGSQKAVE REQERVKSAG AWIIHPYSDF RFYWDFTMLL FMVGNLIIIP VGITFFKDET
   241  TAPWIVFNVV SDTFFLMDLV LNFRTGIVIE DNTEIILDPE KIKKKYLRTW FVVDFVSSIP
   301  VDYIFLIVEK GIDSEVYKTA RALRIVRFTK ILSLLRLLRL SRLIRYIHQW EEIFHMTYDL
   361  ASAVMRICNL ISMMLLLCHW DGCLQFLVPM LQDFPRNCWV SINGMVNHSW SELYSFALFK
   421  AMSHMLCIGY GRQAPESMTD IWLTMLSMIV GATCYAMFIG HATALIQSLD SSRRQYQEKY
   481  KQVEQYMSFH KLPADFRQKI HDYYEHRYQG KMFDEDSILG ELNGPLREEI VNFNCRKLVA
   541  SMPLFANADP NFVTAMLTKL KFEVFQPGDY IIREGTIGKK MYFIQHGVVS VLTKGNKEMK
   601  LSDGSYFGEI CLLTRGRRTA SVRADTYCRL YSLSVDNFNE VLEEYPMMRR AFETVAIDRL
   661  DRIGKKNSIL LHKVQHDLNS GVFNNQENAI IQEIVKYDRE MVQQAELGQR VGLFPPPPPP
   721  PQVTSAIATL QQAAAMSFCP QVARPLVGPL ALGSPRLVRR PPPGPAPAAA SPGPPPPASP
   781  PGAPASPRAP RTSPYGGLPA APLAGPALPA RRLSRASRPL SASQPSLPHG APGPAASTRP
   841  ASSSTPRLGP TPAARAAAPS PDRRDSASPG AAGGLDPQDS ARSRLSSNL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HCN2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
6
Mean surface accessibility (rSASA)
0.46
Highest tissue expression
95 nTPM

Expression across tissuesHPA

Tissue

  • spinal cord: 95 nTPM
  • basal ganglia: 94 nTPM
  • cerebral cortex: 78 nTPM
  • hippocampal formation: 71 nTPM
  • midbrain: 71 nTPM
  • amygdala: 45 nTPM

Single-cell type

  • retinal bipolar cells: 95 nCPM
  • oligodendrocytes: 92 nCPM
  • retinal ganglion cells: 58 nCPM
  • retinal amacrine cells: 32 nCPM
  • brain inhibitory neurons: 26 nCPM
  • retinal horizontal cells: 26 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • thalamus: 377 nTPM
  • cerebral cortex: 300 nTPM
  • cerebellum: 250 nTPM
  • pons: 247 nTPM
  • medulla oblongata: 239 nTPM
  • midbrain: 231 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HCN2.

Disease | AllUniProt

Conditions HCN2 is implicated in, by any mechanism.

  • Epilepsy, idiopathic generalized 17 (EIG17) MIM:602477
  • Febrile seizures, familial, 2 (FEB2) MIM:602477

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 373 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • HCN2 related developmental and epileptic encephalopathy
  • Epilepsy, idiopathic generalized, susceptibility to, 17
  • Febrile seizures, familial, 2
  • Neurodevelopmental delay

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.45
gnomAD pLI
0.49
gnomAD missense Z
3.41
DepMap mean gene effect
-0.17
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of HCN2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HCN2 as an antibody target. Whether an autoantibody or antibody against HCN2 could matter depends on whether native HCN2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HCN2 is annotated at the cell surface, where native HCN2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label HCN2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HCN2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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