Monogenic short stature

Gene: GAP43

Red List (low evidence)

Comment on publications: PMID:39738362 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 25 Mar 2025, 10:12 a.m. | Last Modified: 25 Mar 2025, 10:12 a.m.

Panel Version: 1.13

PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.

There were six previous cases reported with GAP43 abnormalities (3 involving deletion of a region including GAP43, two siblings with duplication and one SNV). Only one of the siblings with region duplication had moderate ID, while the other sibling and another patient with region deletion had mild ID.

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature

Created: 25 Mar 2025, 10:08 a.m. | Last Modified: 25 Mar 2025, 10:13 a.m.

Panel Version: 1.13

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

• 39738362