Seroatlas · Human Serome Atlas

HCN3

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3

Also known as: HCN3_HUMAN, KIAA1535

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

Protein identityUniProt · HPA

UniProt accession
Q9P1Z3
Gene
HCN3
Ensembl
ENSG00000143630
Chromosome
1
Canonical length
774 aa
Protein class
Plasma proteins, Predicted membrane proteins, Voltage-gated ion channels
Quaternary structure
Homotetramer

OverviewNCBI Gene

This gene encodes a multi-pass membrane protein that functions as a voltage gated cation channel. The encoded protein is a member of a family of closely related cyclic adenosine monophosphate-binding channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

Canonical amino-acid sequenceUniProt

774 residues, UniProt reviewed canonical sequence.

>Q9P1Z3|HCN3
     1  MEAEQRPAAG ASEGATPGLE AVPPVAPPPA TAASGPIPKS GPEPKRRHLG TLLQPTVNKF
    61  SLRVFGSHKA VEIEQERVKS AGAWIIHPYS DFRFYWDLIM LLLMVGNLIV LPVGITFFKE
   121  ENSPPWIVFN VLSDTFFLLD LVLNFRTGIV VEEGAEILLA PRAIRTRYLR TWFLVDLISS
   181  IPVDYIFLVV ELEPRLDAEV YKTARALRIV RFTKILSLLR LLRLSRLIRY IHQWEEIFHM
   241  TYDLASAVVR IFNLIGMMLL LCHWDGCLQF LVPMLQDFPP DCWVSINHMV NHSWGRQYSH
   301  ALFKAMSHML CIGYGQQAPV GMPDVWLTML SMIVGATCYA MFIGHATALI QSLDSSRRQY
   361  QEKYKQVEQY MSFHKLPADT RQRIHEYYEH RYQGKMFDEE SILGELSEPL REEIINFTCR
   421  GLVAHMPLFA HADPSFVTAV LTKLRFEVFQ PGDLVVREGS VGRKMYFIQH GLLSVLARGA
   481  RDTRLTDGSY FGEICLLTRG RRTASVRADT YCRLYSLSVD HFNAVLEEFP MMRRAFETVA
   541  MDRLLRIGKK NSILQRKRSE PSPGSSGGIM EQHLVQHDRD MARGVRGRAP STGAQLSGKP
   601  VLWEPLVHAP LQAAAVTSNV AIALTHQRGP LPLSPDSPAT LLARSAWRSA GSPASPLVPV
   661  RAGPWASTSR LPAPPARTLH ASLSRAGRSQ VSLLGPPPGG GGRRLGPRGR PLSASQPSLP
   721  QRATGDGSPG RKGSGSERLP PSGLLAKPPR TAQPPRPPVP EPATPRGLQL SANM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HCN3 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)
0.44
Highest tissue expression
20 nTPM

Expression across tissuesHPA

Tissue

  • cerebellum: 20 nTPM
  • hypothalamus: 7.4 nTPM
  • pituitary gland: 6.9 nTPM
  • skin: 5.4 nTPM
  • cerebral cortex: 5 nTPM
  • colon: 4.6 nTPM

Single-cell type

  • other brain neurons: 12 nCPM
  • brain inhibitory neurons: 10 nCPM
  • brain excitatory neurons: 7.7 nCPM
  • proximal tubule cells: 6.2 nCPM
  • oligodendrocyte progenitor cells: 5.7 nCPM
  • renal connecting tubule cells: 4.9 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

  • cerebellum: 12 nTPM
  • hypothalamus: 11 nTPM
  • pons: 11 nTPM
  • midbrain: 9 nTPM
  • thalamus: 8.2 nTPM
  • cerebral cortex: 8.1 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HCN3.

Disease | ImmuneIEDB

Conditions an epitope on HCN3 was assayed in.

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)
0.74
gnomAD pLI
0
gnomAD missense Z
1.52
DepMap mean gene effect
-0.03
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% 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 HCN3 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 HCN3 as an antibody target. Whether an autoantibody or antibody against HCN3 could matter depends on whether native HCN3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HCN3 is annotated at the cell surface, where native HCN3 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 HCN3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HCN3. 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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