KLHL9

Chr 9

kelch like family member 9

NCBI Gene: 55958 ENSG00000198642 UniProt: Q9P2J3 OMIM: 611201

The protein functions as a substrate-specific adapter in a cullin 3-based E3 ubiquitin ligase complex that regulates mitotic progression and cytokinesis by controlling aurora B kinase localization and activity during cell division. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and neurological abnormalities. This gene is highly constrained against loss-of-function variants (pLI = 0.82, LOEUF = 0.41), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain, a BACK domain and six C-terminal kelch repeats. The encoded protein is a component of a complex with cullin 3-based E3 ligase, which plays a role in mitosis. This protein complex is a cell cycle regulator, and functions in the organization and integrity of the spindle midzone in anaphase and the completion of cytokinesis. The complex is required for the removal of the chromosomal passenger protein aurora B from mitotic chromosomes. [provided by RefSeq, Jul 2016]

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

0.41

LOEUF

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Mechanism