Seroatlas · Human Serome Atlas

KCNA4

Potassium voltage-gated channel subfamily A member 4

Also known as: HK1, HPCN2, KCNA4_HUMAN, KCNA4L, Kv1.4, PCN2

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

Protein identityUniProt · HPA

UniProt accession
P22459
Gene
KCNA4
Ensembl
ENSG00000182255
Chromosome
11
Canonical length
653 aa
Protein class
Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted membrane proteins, Transporters, Voltage-gated ion channels
Quaternary structure
Homotetramer

OverviewNCBI Gene

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the A-type potassium current class, the members of which may be important in the regulation of the fast repolarizing phase of action potentials in heart and thus may influence the duration of cardiac action potential.[provided by RefSeq, Mar 2011]

Canonical amino-acid sequenceUniProt

653 residues, UniProt reviewed canonical sequence.

>P22459|KCNA4
     1  MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRAAA AAAVAAATAA VEGSGGSGGG
    61  SHHHHQSRGA CTSHDPQSSR GSRRRRRQRS EKKKAHYRQS SFPHCSDLMP SGSEEKILRE
   121  LSEEEEDEEE EEEEEEEGRF YYSEDDHGDE CSYTDLLPQD EGGGGYSSVR YSDCCERVVI
   181  NVSGLRFETQ MKTLAQFPET LLGDPEKRTQ YFDPLRNEYF FDRNRPSFDA ILYYYQSGGR
   241  LKRPVNVPFD IFTEEVKFYQ LGEEALLKFR EDEGFVREEE DRALPENEFK KQIWLLFEYP
   301  ESSSPARGIA IVSVLVILIS IVIFCLETLP EFRDDRDLVM ALSAGGHGGL LNDTSAPHLE
   361  NSGHTIFNDP FFIVETVCIV WFSFEFVVRC FACPSQALFF KNIMNIIDIV SILPYFITLG
   421  TDLAQQQGGG NGQQQQAMSF AILRIIRLVR VFRIFKLSRH SKGLQILGHT LRASMRELGL
   481  LIFFLFIGVI LFSSAVYFAE ADEPTTHFQS IPDAFWWAVV TMTTVGYGDM KPITVGGKIV
   541  GSLCAIAGVL TIALPVPVIV SNFNYFYHRE TENEEQTQLT QNAVSCPYLP SNLLKKFRSS
   601  TSSSLGDKSE YLEMEEGVKE SLCAKEEKCQ GKGDDSETDK NNCSNAKAVE TDV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KCNA4 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
7.9 nTPM

Expression across tissuesHPA

Tissue

  • basal ganglia: 7.9 nTPM
  • adrenal gland: 5.8 nTPM
  • cerebral cortex: 2.4 nTPM
  • heart muscle: 2 nTPM
  • retina: 1.7 nTPM
  • adipose tissue: 1.4 nTPM

Single-cell type

  • corticotrophs: 28 nCPM
  • thyrotrophs: 22 nCPM
  • brain inhibitory neurons: 21 nCPM
  • retinal horizontal cells: 18 nCPM
  • podocytes: 17 nCPM
  • mesothelial cells: 16 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

  • basal ganglia: 56 nTPM
  • cerebral cortex: 28 nTPM
  • hippocampal formation: 24 nTPM
  • thalamus: 23 nTPM
  • hypothalamus: 21 nTPM
  • amygdala: 19 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KCNA4.

Disease | AllUniProt

Conditions KCNA4 is implicated in, by any mechanism.

  • Microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum (MCIDDS) MIM:618284

Disease | AutoantibodyPubMed

Conditions in which antibodies against KCNA4 are reported. Each links to that disease's full target list.

ReferencesPubMed · IEDB

Publications for KCNA4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

15 publications

Show 10 more

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)
0.28
gnomAD pLI
0.98
gnomAD missense Z
2.03
DepMap mean gene effect
-0.07
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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 KCNA4 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 KCNA4 as an antibody target. Whether an autoantibody or antibody against KCNA4 could matter depends on whether native KCNA4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

KCNA4 is annotated at the cell surface, where native KCNA4 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 KCNA4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/KCNA4. 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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