KLHL20

Chr 1AD

kelch like family member 20

Also known as: KHLHX, KLEIP, KLHLX, NEDSZFB

NCBI Gene: 27252 ENSG00000076321 UniProt: Q9Y2M5 OMIM: 617679

The protein functions as a substrate-specific adapter of a BCR E3 ubiquitin ligase complex that regulates protein degradation, Golgi to endosome transport, and neurite outgrowth. Mutations cause a neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.511), consistent with its role in early neurodevelopment.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the kelch family of proteins, which is characterized by a 44-56 amino acid repeat motif. The kelch motif appears in many different polypeptide contexts and contains multiple potential protein-protein contact sites. Members of this family are present both throughout the cell and extracellularly, with diverse activities. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalitiesMIM #621390

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADModerateconsider for supplementary testing

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.51

LOEUF

Multiple*

Mechanism· predicted