TBK1

Chr 12ADAR

TANK binding kinase 1

Also known as: AIARV, FTDALS4, IIAE8, NAK, T2K

NCBI Gene: 29110 ENSG00000183735 UniProt: Q9UHD2 OMIM: 604834

TBK1 encodes a kinase that phosphorylates IκB proteins to activate NF-κB signaling and mediates antiviral innate immunity responses. Mutations cause autosomal dominant frontotemporal dementia and/or amyotrophic lateral sclerosis 4, autosomal recessive autoinflammation with arthritis and vasculitis, and susceptibility to herpes-specific acute encephalopathy. The pathogenic mechanism involves disrupted NF-κB activation and impaired antiviral immunity.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. The protein is also an important kinase for antiviral innate immunity response. [provided by RefSeq, Sep 2021]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8}MIM #617900

Autoinflammation with arthritis and vasculitisMIM #620880

Frontotemporal dementia and/or amyotrophic lateral sclerosis 4MIM #616439

UniProtGlaucoma 1, open angle, P

Clinical highlights

Gene-disease validity (ClinGen)

frontotemporal dementia and/or amyotrophic lateral sclerosis 4 · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

715

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

Multiple*

Mechanism· predicted

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