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  3. INPP4A
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Intellectual disability syndromic and non-syndromic

Gene: INPP4A

Green List (high evidence)
INPP4A (inositol polyphosphate-4-phosphatase type I A)
EnsemblGeneIds (GRCh38): ENSG00000040933
EnsemblGeneIds (GRCh37): ENSG00000040933
OMIM: 600916, Gene2Phenotype
INPP4A is in 7 panels

2 reviews

Chirag Patel (Genetic Health Queensland)

Green List (high evidence)

PMID: 39315527
30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4).

Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4.

Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain.
Created: 16 Jan 2025, 4:25 a.m. | Last Modified: 16 Jan 2025, 4:25 a.m.
Panel Version: 1.43

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
INPP4A-related neurodevelopmental disorder

Publications

Created: 16 Jan 2025, 4:25 a.m.
Last Modified: 16 Jan 2025, 4:25 a.m.
Panel version: 1.43

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Two families reported with bi-allelic variants and a neurological phenotype. Supportive mouse model and expression data.
Sources: Literature
Created: 21 Mar 2021, 7:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability

Publications

Created: 21 Mar 2021, 7:27 a.m.

Panel version: 0.3540

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Intellectual disability
OMIM
600916
Clinvar variants
Variants in INPP4A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

16 Jan 2025, Gel status: 3

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

Gene: inpp4a has been classified as Green List (High Evidence).

21 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: inpp4a has been classified as Amber List (Moderate Evidence).

21 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: inpp4a has been classified as Amber List (Moderate Evidence).

21 Mar 2021, Gel status: 1

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: INPP4A was added gene: INPP4A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INPP4A were set to 31978615; 31938306; 25338135; 20011524 Phenotypes for gene: INPP4A were set to Intellectual disability Review for gene: INPP4A was set to AMBER