Intellectual disability
Gene: EIF1AX

EIF1AX (eukaryotic translation initiation factor 1A, X-linked)
EnsemblGeneIds (GRCh38): ENSG00000173674
EnsemblGeneIds (GRCh37): ENSG00000173674
OMIM: 300186, Gene2Phenotype
EIF1AX is in 1 panel

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Julia Baptista, there is sufficient evidence available (four unrelated cases) for the association of EIF1AX with intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 6 Aug 2026, 9:38 a.m. | Last Modified: 6 Aug 2026, 9:38 a.m.

Panel Version: 10.94

PMID:42337333 (2026) reported the identification of four different de novo hemizygous variants in EIF1AX gene in four unrelated male individuals with a syndromic neurodevelopmental disorder consisting of variable neurodevelopmental delay, dysmorphic features, behavioral problems, ophthalmological abnormalities, and structural abnormalities in the brain. Intellectual disability and/ or global developmental delay were reported in all four patients. Growth failure with SD <-3 was reported in three of these four individuals.

The c.204 G > C variant was predicted to cause a splicing alteration, and minigene analysis confirmed exon skipping leading to the generation of a premature termination codon. Functional studies using transgenic Drosophila harboring wild-type EIF1AX or the three other EIF1AX missense variants showed that overexpression of WT and the p.(Asn17Asp) variant cause structural abnormalities in the compound eye, whereas the p.(Lys64Glu) and p.(Asp90Gly) variants significantly reduce these eye abnormalities.

This gene has not yet been associated with relevant phenotypes in OMIM, Gene2Phenotype or ClinGen (last accessed 06 August 2026).
Created: 6 Aug 2026, 9:32 a.m. | Last Modified: 6 Aug 2026, 9:32 a.m.

Panel Version: 10.90

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

42337333

Created: 6 Aug 2026, 9:32 a.m.
Last Modified: 6 Aug 2026, 9:32 a.m.
Panel version: 10.90

Julia Baptista (South East Genomic Laboratory Hub, Synnovis, King's College Hospital)

Green List (high evidence)

PMID: 42337333- describes four de novo hemizygous EIF1AX variants (comprising three missense and one splice variant) in four male individuals exhibiting variable neurodevelopmental disorders, including developmental and language delays, autistic behavioral problems, and facial dysmorphisms.
Functional studies using Drosophila models supported a LOF effect for (Lys64Glu) and p.(Asp90Gly) whilst no significant effect was seen for p.(Asn17Asp). Minigene analysis for the c.204 G > C showed aberrant mRNA splicing and a LOF allele.
Sources: Literature
Created: 4 Aug 2026, 1:33 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
intellectual disability

Publications

PMID: 42337333

Created: 4 Aug 2026, 1:33 p.m.

Panel version: 10.85

Details

Mode of Inheritance

X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Sources

Expert Review Amber

Phenotypes

neurodevelopmental disorder, MONDO:0700092

Tags

Q3_26_NHS_review Q3_26_promote_green

OMIM

300186

Clinvar variants

Variants in EIF1AX

Penetrance

None

Publications

42337333

Panels with this gene

Intellectual disability