Severe microcephaly

Gene: SNAPIN

I don't know

Comment on list classification: Although there are three unrelated patients reported with microcephaly (excluding foetuses), only one had information on severity of microcephaly (being severe - -8SD). Hence, this gene can only be rated amber with current evidence.

Created: 2 Jan 2026, 7:56 p.m. | Last Modified: 2 Jan 2026, 7:57 p.m.

Panel Version: 8.23

PMID:26539891 (2015) reported whole exome sequencing of 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. One of these patients was identified with homozygous variant in SNAPIN gene (c.163C>T/ p.Arg55Trp). The patient displayed intellectual disability, microcephaly, cortical atrophy, bulbar and cerebellar hypoplasia, sensorineural polyneuropathy and hypotonia. The severity of microcephaly is not available in the publication.

PMID:40930097 (2025) reported six patients from five unrelated families presenting with neuroanatomical, craniofacial, and skeletal anomalies and were identified with homozygous variants in SNAPIN gene. This included four foetuses from three unrelated families (had nonsense or splice site variants - c.91G>T/ p.Glu31Ter, c.144−1G>A & c.112C>T/ p.Gln38Ter) and two unrelated patients aged eight years old and one year old (had missense variants - c.147G>C/ p.Glu49Asp & c.163C>T/ p.Arg55Trp). The eight-year-old patient had severe microcephaly (−8 SD), while severity of microcephaly was not recorded for one-year-old patient.

Functional evidence is also available from zebrafish gene ablation models, which recapitulated human-relevant disease phenotypes.

This gene has been associated with relevant phenotype in OMIM (MIM #621393, last accessed on 02 January 2026), but not yet in Gene2Phenotype or ClinGen.
Sources: Literature

Created: 2 Jan 2026, 7:54 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, OMIM:621393

Publications

• 26539891
• 40930097