Intellectual disability
Gene: FOSL2

FOSL2 (FOS like 2, AP-1 transcription factor subunit)
EnsemblGeneIds (GRCh38): ENSG00000075426
EnsemblGeneIds (GRCh37): ENSG00000075426
OMIM: 601575, Gene2Phenotype
FOSL2 is in 5 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 24 Feb 2025, 6:15 p.m. | Last Modified: 24 Feb 2025, 6:15 p.m.

Panel Version: 8.97

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 24 Feb 2025, 6:15 p.m.
Last Modified: 24 Feb 2025, 6:15 p.m.
Panel version: 8.97

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available for the association of this gene with green rating in the next GMS update.
Created: 3 Oct 2024, 2:21 p.m. | Last Modified: 3 Oct 2024, 2:21 p.m.

Panel Version: 7.55

PMID:36197437 reported 11 individuals from 10 unrelated families with heterozygous PTC variants (4 frameshift and 3 nonsense) in the last exon of FOSL2 gene. They all had a strikingly similar phenotype characterized by prenatal growth retardation, localized cutis scalp aplasia with or without skull defects, neurodevelopmental delay with autism spectrum disorder, enamel hypoplasia, and congenital cataracts.

Seven out of nine reported individuals had delayed psychomotor development or intellectual disability (ID), of which ID was mild in four individuals and severe in two individuals. Motor and language development were delayed for most patients, but first words were spoken before 3 years of age.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620789) and Gene2Phenotype (with 'moderate' rating on the DD panel).
Created: 3 Oct 2024, 2:16 p.m. | Last Modified: 3 Oct 2024, 2:16 p.m.

Panel Version: 7.53

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Aplasia cutis-enamel dysplasia syndrome, OMIM:620789

Publications

36197437

Created: 3 Oct 2024, 2:16 p.m.
Last Modified: 3 Oct 2024, 2:16 p.m.
Panel version: 7.53

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

Already in OMIM as Aplasia cutis-enamel dysplasia syndrome. PMID: 36197437 described 10 cases with NDD and aplasia cutis and truncating variants in the last exon of FOSL2.
Sources: Literature
Created: 28 Aug 2024, 6:23 p.m. | Last Modified: 28 Aug 2024, 6:24 p.m.

Panel Version: 7.18

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Aplasia cutis-enamel dysplasia syndrome

Publications

PMID: 36197437

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Created: 28 Aug 2024, 6:23 p.m.
Last Modified: 28 Aug 2024, 6:24 p.m.
Panel version: 7.18

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS

Phenotypes

Aplasia cutis-enamel dysplasia syndrome, OMIM:620789

OMIM

601575

Clinvar variants

Variants in FOSL2

Penetrance

None

Publications

36197437

Mode of Pathogenicity

Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Panels with this gene

History Filter Activity

25 Feb 2025, Gel status: 3

Removed Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_24_promote_green was removed from gene: FOSL2.

24 Feb 2025, Gel status: 3

Added New Source, Added New Source, Status Update

Sarah Leigh (Genomics England Curator)

Source NHS GMS was added to FOSL2. Source Expert Review Green was added to FOSL2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

3 Oct 2024, Gel status: 2