GLE1

Chr 9AR

GLE1 RNA export mediator

Also known as: CAAHC, CAAHD, GLE1L, LCCS, LCCS1, hGLE1

The protein is required for export of polyadenylated mRNAs from the nucleus to the cytoplasm through nuclear pore complexes. Mutations cause arthrogryposis multiplex congenita neurogenic type (Lethal Congenital Contracture Syndrome) and ataxia with oculomotor apraxia, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.752), reflecting its essential cellular function.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismARLOEUF 0.752 OMIM phenotypes
Clinical SummaryGLE1
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Gene-Disease Validity (ClinGen)
amyotrophic lateral sclerosis · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.000
Z-score 2.86
OE 0.53 (0.380.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.81Z-score
OE missense 0.88 (0.810.97)
335 obs / 379.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.380.75)
00.351.4
Missense OE0.88 (0.810.97)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 23 / 43.3Missense obs/exp: 335 / 379.1Syn Z: 0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGLE1-related arthrogryposis, lethal, with anterior horn cell diseaseOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6163th %ile
GOF
0.6639th %ile
LOF
0.3358th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GLE1 · 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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