Severe microcephaly

Gene: EIPR1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 5 Jan 2026, 6:48 p.m. | Last Modified: 5 Jan 2026, 6:48 p.m.

Panel Version: 8.27

PMID:41058046 (2025) reported the identification of five EIPR1 homozygous missense variants (c.835C>G/ p.Arg279Gly, c.813C>G/ p.His271Gln, c.694C>T/ p.Arg232Trp, c.47G>A/ p.Arg16His and c.419T>A/ p.Val140Asp) in eight individuals from six unrelated families with a neurological disorder featuring a spectrum of global neurodevelopmental delay, microcephaly, ataxia, spasticity, delayed myelination, callosal hypoplasia, cerebellar atrophy, walking and speech impairments, dysmorphic facies, and neutropenia. Microcephaly was present in five patients from three unrelated families, of which three patients from two families had Severe microcephaly (OFC beyond -3SD).

There is also functional evidence available from cellular studies using a heterologous transfection system, kin fibroblasts from one of the Arg279Gly affected individuals and zebrafish knockout model. Knockout of the orthologous eipr1 in zebrafish resulted in neurodevelopmental and locomotor defects consistent with the clinical phenotype of the human patients.

This gene has not yet been associated with any phenotypes in OMIM (last accessed 05 January 2026), Gene2Phenotype or ClinGen.
Sources: Literature

Created: 5 Jan 2026, 6:47 p.m. | Last Modified: 6 Jan 2026, 5:41 p.m.

Panel Version: 8.27

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 41058046