HIKESHI

Chr 11AR

heat shock protein nuclear import factor hikeshi

Also known as: C11orf73, HLD13, HSPC138, HSPC179, L7RN6, OPI10

NCBI Gene: 51501 ENSG00000149196 UniProt: Q53FT3 OMIM: 614908

The protein functions as a nuclear transport receptor that specifically imports ATP-bound HSP70 heat shock proteins into the nucleus during cellular stress responses. Mutations cause hypomyelinating leukodystrophy 13, an autosomal recessive disorder affecting white matter development in the brain. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), suggesting some tolerance to functional disruption.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an evolutionarily conserved nuclear transport receptor that mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins (Hsp70s) through interactions with FG-nucleoporins. The protein mediates transport of the ATP form but not the ADP form of Hsp70 proteins under conditions of heat shock stress. Structural analyses demonstrate that the protein forms an asymmetric homodimer and that the N-terminal domain consists of a jelly-roll/beta-sandwich fold structure that contains hydrophobic pockets involved in FG-nucleoporin recognition. Reduction of RNA expression levels in HeLa cells using small interfering RNAs results in inhibition of heat shock-induced nuclear accumulation of Hsp70s, indicating a role for this gene in regulation of Hsp70 nuclear import during heat shock stress. [provided by RefSeq, Apr 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Leukodystrophy, hypomyelinating, 13MIM #616881

Clinical highlights

Gene-disease validity (ClinGen)

hypomyelinating leukodystrophy 13 · ARDefinitivesufficient 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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.59

LOEUF

Mechanism· predicted

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GeneReview available — HIKESHI

Authoritative clinical overview · Recommended first read