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Intellectual disability syndromic and non-syndromic

Gene: POU3F2

Green List (high evidence)

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

Mode of pathogenicity
Other

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
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

1 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Ain Roesley (Victorian Clinical Genetics Services)

Gene: pou3f2 has been classified as Green List (High Evidence).

1 Jun 2023, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related

1 Jun 2023, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related

1 Jun 2023, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related

1 Jun 2023, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related

1 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Ain Roesley (Victorian Clinical Genetics Services)

Gene: pou3f2 has been classified as Green List (High Evidence).

1 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Ain Roesley (Victorian Clinical Genetics Services)

Gene: pou3f2 has been classified as Green List (High Evidence).

1 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Ain Roesley (Victorian Clinical Genetics Services)

Gene: pou3f2 has been classified as Green List (High Evidence).

1 Jun 2023, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance, Set mode of pathogenicity

Sarah Pantaleo (Victorian Clinical Genetics Services)

gene: POU3F2 was added gene: POU3F2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU3F2 were set to PMID: 37207645 Phenotypes for gene: POU3F2 were set to Autism spectrum disorder, NDD, and adolescent-onset obesity Penetrance for gene: POU3F2 were set to unknown Mode of pathogenicity for gene: POU3F2 was set to Other Review for gene: POU3F2 was set to GREEN