KPNA3

Chr 13

karyopherin subunit alpha 3

Also known as: IPOA4, SPG88, SRP1, SRP1gamma, SRP4, hSRP1

NCBI Gene: 3839 ENSG00000102753 UniProt: O00505

The protein functions as an adapter for nuclear protein import, binding to nuclear localization signals on substrate proteins and facilitating their transport into the nucleus through the nuclear pore complex. Mutations cause spastic paraplegia 88 with autosomal dominant inheritance, affecting the spinal cord and leading to progressive lower limb spasticity. The gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.33), indicating that haploinsufficiency is likely not tolerated in the general population.

ResearchSummary from RefSeq, OMIM, UniProt

The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import. [provided by RefSeq, Jan 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 88, autosomal dominant

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

0.33

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

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