XPO6

Chr 16

exportin 6

Also known as: EXP6, RANBP20

NCBI Gene: 23214 ENSG00000169180 UniProt: Q96QU8 OMIM: 608411

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the importin-beta family. Members of this family are regulated by the GTPase Ran to mediate transport of cargo across the nuclear envelope. This protein has been shown to mediate nuclear export of profilin-actin complexes. A pseudogene of this gene is located on the long arm of chromosome 14. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.08

Clinical Summary— XPO6

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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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ClinVar Variants

100 VUS of 136 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.08LOEUF

pLI 1.000

Z-score 6.92

OE 0.02 (0.01–0.08)

Highly constrained

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

Missense Constraint?

3.48Z-score

OE missense 0.61 (0.56–0.67)

396 obs / 645.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.08)

0≤0.351.4

Missense OE?0.61 (0.56–0.67)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 1 / 57.8Missense obs/exp: 396 / 645.1Syn Z: -0.18

This gene — mechanism propensity

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

136 submitted variants in ClinVar

ClinVar

Classification Summary

VUS100

Likely Benign1

Benign1

100

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	100	0	100
Likely Benign	0	1	1
Benign	0	1	1
Total	100	2	102

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap XPO6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →