Intellectual disability syndromic and non-syndromic
Gene: WIPI2

WIPI2 (WD repeat domain, phosphoinositide interacting 2)
EnsemblGeneIds (GRCh38): ENSG00000157954
EnsemblGeneIds (GRCh37): ENSG00000157954
OMIM: 609225, Gene2Phenotype
WIPI2 is in 2 panels

2 reviews

Dean Phelan (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID: 30968111 (2019)
- homozygous missense variant identified in 4 patients from a highly consanguineous Pakistani family with intellectual developmental disorder with short stature and variable skeletal anomalies.
- functional studies showed reduced binding and reduced WIPI2 puncta, reduced LC3 lipidation and reduced autophagic flux.

PMID: 34557665 (2021)
- two novel homozygous variants were identified in four individuals of two consanguineous families.
- one family presented with microcephaly, profound global developmental delay/intellectual disability, refractory infantile/childhood-onset epilepsy, progressive tetraplegia with joint contractures and dyskinesia.
- second family (similar to initial publication) presented with a milder phenotype, encompassing moderate intellectual disability, speech and visual impairment, autistic features, and an ataxic gait.
- functional studies showed dysregulation of the early steps of the autophagy pathway.
Created: 4 Oct 2021, 4:54 a.m. | Last Modified: 4 Oct 2021, 4:54 a.m.

Panel Version: 0.4164

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
global developmental delay; intellectual disability; refractory infantile/childhood-onset epilepsy; progressive tetraplegia with joint contractures; dyskinesia; speech and visual impairment; autistic features; ataxic gait

Publications

PMID: 30968111
34557665

Variants in this GENE are reported as part of current diagnostic practice

Created: 4 Oct 2021, 4:54 a.m.
Last Modified: 4 Oct 2021, 4:54 a.m.
Panel version: 0.4164

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

Four homozygous individuals from one consanguineous family with intellectual disability, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function.
Sources: Literature
Created: 20 Apr 2020, 10:12 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder with short stature and variable skeletal anomalies 618453

Publications

30968111

Created: 20 Apr 2020, 10:12 a.m.

Panel version: 0.2545

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Literature

Phenotypes

Intellectual developmental disorder with short stature and variable skeletal anomalies 618453
global developmental delay
intellectual disability
refractory infantile/childhood-onset epilepsy
progressive tetraplegia with joint contractures
dyskinesia
speech and visual impairment
autistic features
ataxic gait

OMIM

609225

Clinvar variants

Variants in WIPI2

Penetrance

None

Publications

Panels with this gene