XPO4

Chr 13

exportin 4

Also known as: exp4

XPO4 encodes exportin-4, a nuclear transport receptor that mediates the export of specific proteins from the nucleus to the cytoplasm, including translation factor EIF5A and transcription regulators like SMAD3. Mutations cause autosomal dominant intellectual disability with microcephaly and seizures, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that proper nuclear export function is essential for normal neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.14
Clinical SummaryXPO4
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
44 unique Pathogenic / Likely Pathogenic· 103 VUS of 164 total submissions
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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
0.14LOEUF
pLI 1.000
Z-score 6.96
OE 0.06 (0.030.14)
Highly constrained

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

Missense Constraint
4.02Z-score
OE missense 0.53 (0.480.58)
313 obs / 587.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.030.14)
00.351.4
Missense OE0.53 (0.480.58)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 4 / 64.2Missense obs/exp: 313 / 587.2Syn Z: 1.20

ClinVar Variant Classifications

164 submitted variants in ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS103
Likely Benign1
Benign1
42
Pathogenic
2
Likely Pathogenic
103
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
2
0
2
VUS
0
91
12
0
103
Likely Benign
0
0
0
1
1
Benign
0
0
0
1
1
Total091562149

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

View in ClinVar →

Protein Context — Lollipop Plot

XPO4 · 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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