KLHL22

Chr 22

kelch like family member 22

Also known as: KELCHL

NCBI Gene: 84861 ENSG00000099910 UniProt: Q53GT1 OMIM: 618020

KLHL22 encodes a substrate-specific adapter protein that functions as part of a ubiquitin ligase complex, mediating chromosome alignment during cell division and regulating the mTORC1 pathway through degradation of DEPDC5. Mutations cause autosomal recessive developmental and epileptic encephalopathy with early-onset seizures and developmental delay. The gene shows significant constraint against loss-of-function variants (LOEUF 0.44), indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Enables 14-3-3 protein binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including cellular response to L-leucine; mitotic spindle assembly checkpoint signaling; and positive regulation of TORC1 signaling. Located in several cellular components, including intercellular bridge; lysosome; and microtubule cytoskeleton. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.44

LOEUF

GOF

Mechanism· predicted