KCNJ11

Protein identityUniProt · HPA

UniProt accession

Q14654

Gene

KCNJ11

Ensembl

ENSG00000187486

Chromosome

11

Canonical length

390 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters, Voltage-gated ion channels

Quaternary structure

Homotetramer

OverviewNCBI Gene

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

390 residues, UniProt reviewed canonical sequence.

>Q14654|KCNJ11
     1  MLSRKGIIPE EYVLTRLAED PAKPRYRARQ RRARFVSKKG NCNVAHKNIR EQGRFLQDVF
    61  TTLVDLKWPH TLLIFTMSFL CSWLLFAMAW WLIAFAHGDL APSEGTAEPC VTSIHSFSSA
   121  FLFSIEVQVT IGFGGRMVTE ECPLAILILI VQNIVGLMIN AIMLGCIFMK TAQAHRRAET
   181  LIFSKHAVIA LRHGRLCFML RVGDLRKSMI ISATIHMQVV RKTTSPEGEV VPLHQVDIPM
   241  ENGVGGNSIF LVAPLIIYHV IDANSPLYDL APSDLHHHQD LEIIVILEGV VETTGITTQA
   301  RTSYLADEIL WGQRFVPIVA EEDGRYSVDY SKFGNTVKVP TPLCTARQLD EDHSLLEALT
   361  LASARGPLRK RSVPMAKAKP KFSISPDSLS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KCNJ11 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

2

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

106 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KCNJ11.

Disease | AllUniProt

Conditions KCNJ11 is implicated in, by any mechanism.

• Hyperinsulinemic hypoglycemia, familial, 2 (HHF2) MIM:601820
• Diabetes mellitus, permanent neonatal, 2 (PNDM2) MIM:618856
• Diabetes mellitus, transient neonatal, 3 (TNDM3) MIM:610582
• Maturity-onset diabetes of the young 13 (MODY13) MIM:616329

Disease | GeneticClinVar

76 pathogenic / likely-pathogenic of 565 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Permanent neonatal diabetes mellitus
• Type 2 diabetes mellitus
• Hyperinsulinemic hypoglycemia, familial, 2
• Diabetes mellitus, transient neonatal, 3
• Diabetes mellitus, permanent neonatal 2

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)

1.21

gnomAD pLI

0.01

gnomAD missense Z

1.65

DepMap mean gene effect

-0.01

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

• action potential
• apoptotic process
• CAMKK-AMPK signaling cascade
• cellular response to nutrient levels
• determination of adult lifespan
• glucose metabolic process
• inorganic cation transmembrane transport
• negative regulation of insulin secretion
• nervous system process
• potassium ion import across plasma membrane
• potassium ion transmembrane transport
• regulation of insulin secretion
• regulation of membrane potential
• regulation of monoatomic ion transmembrane transport
• response to ATP
• response to hypoxia
• response to ischemia
• response to resveratrol
• response to xenobiotic stimulus
• ventricular cardiac muscle tissue development

Molecular functions

• ankyrin binding
• ATP binding
• ATP-activated inward rectifier potassium channel activity
• ATPase-coupled monoatomic cation transmembrane transporter activity
• potassium ion binding
• transmembrane transporter binding
• voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
• voltage-gated potassium channel activity

Cellular components

• cytoplasm
• inward rectifying potassium channel
• plasma membrane
• T-tubule

Protein domainsUniProt · Pfam · InterPro

• Potassium channel, inwardly rectifying, Kir, cytoplasmic
• Immunoglobulin E-set
• Potassium channel, inwardly rectifying, Kir
• Potassium channel, inwardly rectifying, transmembrane domain
• Inward rectifier potassium channel, C-terminal
• Inward rectifier potassium channel transmembrane domain
• Inward rectifier potassium channel C-terminal domain
• Potassium channel, inwardly rectifying, Kir6.2

KeywordsUniProt

• ATP-binding
• Diabetes mellitus
• Disulfide bond
• Ion channel
• Ion transport
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Potassium
• Potassium transport
• Transmembrane
• Transmembrane helix
• Transport
• Voltage-gated channel

InteractionsUniProt · HPA

Protein binding partners of KCNJ11 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ABCC9