KPNA3

Chr 13AD

karyopherin subunit alpha 3

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

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Spastic paraplegia 88, autosomal dominantMIM #620106
AD
0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.33
LOEUF· LoF intol.
Mechanism
Clinical SummaryKPNA3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.33LOEUF
pLI 0.954
Z-score 4.39
OE 0.16 (0.080.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.39Z-score
OE missense 0.41 (0.350.48)
110 obs / 265.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.16 (0.080.33)
00.351.4
Missense OE0.41 (0.350.48)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 5 / 31.7Missense obs/exp: 110 / 265.6Syn Z: -0.59

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KPNA3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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