IPO8

Chr 12AR

importin 8

Also known as: RANBP8, VISS

NCBI Gene: 10526 ENSG00000133704 UniProt: O15397 OMIM: 605600

IPO8 encodes importin-8, a nuclear transport receptor that mediates the import of proteins from the cytoplasm into the nucleus through nuclear pore complexes in a Ran-GTP dependent manner. Biallelic mutations cause VISS syndrome (vertebral, cardiac, intellectual disability, and seizures syndrome), an autosomal recessive disorder. The gene shows significant constraint against loss-of-function variants (LOEUF 0.358), consistent with its essential role in nuclear protein transport.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. This protein binds to the nuclear pore complex and, along with RanGTP and RANBP1, inhibits the GAP stimulation of the Ran GTPase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

VISS syndromeMIM #619472

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.36

LOEUF

LOF

Mechanism· G2P

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GeneReview available — IPO8