XPO6

Chr 16

exportin 6

Also known as: EXP6, RANBP20

This protein mediates nuclear export of actin and profilin-actin complexes from the nucleus to the cytoplasm. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and brain malformations. The gene is extremely intolerant to loss-of-function variants, indicating that proper dosage is critical for normal neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.08
Clinical SummaryXPO6
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 6.92
OE 0.02 (0.010.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.48Z-score
OE missense 0.61 (0.560.67)
396 obs / 645.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.010.08)
00.351.4
Missense OE0.61 (0.560.67)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 1 / 57.8Missense obs/exp: 396 / 645.1Syn Z: -0.18
DN
0.3296th %ile
GOF
0.4481th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.08

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

XPO6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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