Intellectual disability syndromic and non-syndromic
Gene: POU3F2

POU3F2 (POU class 3 homeobox 2)
EnsemblGeneIds (GRCh38): ENSG00000184486
EnsemblGeneIds (GRCh37): ENSG00000184486
OMIM: 600494, Gene2Phenotype
POU3F2 is in 2 panels

1 review

Sarah Pantaleo (Victorian Clinical Genetics Services)

Green List (high evidence)

Both loss of function and gain of function demonstrated
Created: 1 Jun 2023, 1:31 a.m. | Last Modified: 1 Jun 2023, 1:31 a.m.

Panel Version: 0.5234

We associate ultra-rare variants in POU3F2, encoding a central nervous system transcription factor, with syndromic obesity and neurodevelopment delay in 12 individuals. Demonstrate variant pathogenicity through in vitro analysis. Used exome sequencing, GeneMatcher and Genomics England 100,000 Genomes Project rare disease database.

Both truncating and missense variants in over 10 individuals sharing autism spectrum disorder, NDD, and adolescent-onset obesity (may have had other features eg. CAKUT in 2 individuals, diabetes in two) . Affected individuals presented with low-to-normal birth weight and infantile feeding difficulties but developed insulin resistance and hyperplasia during childhood. With the exception of an early truncating variant, the variants showed adequate nuclear translocation but overall disturbed DNA-binding ability and promoter activation.

Variants absent from population and clinical databases. Almost all constituted putatively non-inherited de novo variants (8/10).

Functional studies provide evidence for loss of function in eight and gain of function in one obesity-associated POU3F2 variant. One variant did not impact POU3F2-promoter activation, leaving the possibility for further path-mechanisms.
Sources: Literature
Created: 1 Jun 2023, 1:30 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autism spectrum disorder, NDD, and adolescent-onset obesity

Publications

PMID: 37207645

Mode of pathogenicity
Other

Created: 1 Jun 2023, 1:30 a.m.

Panel version: 0.5234

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green

Phenotypes

Autism spectrum disorder, NDD, and adolescent-onset obesity
neurodevelopmental disorder MONDO:0700092, POU3F2-related

OMIM

600494

Clinvar variants

Variants in POU3F2

Penetrance

unknown

Publications

PMID: 37207645

Mode of Pathogenicity

Other

Panels with this gene