Intellectual disability
Gene: ATP2B2

ATP2B2 (ATPase plasma membrane Ca2+ transporting 2)
EnsemblGeneIds (GRCh38): ENSG00000157087
EnsemblGeneIds (GRCh37): ENSG00000157087
OMIM: 108733, Gene2Phenotype
ATP2B2 is in 4 panels

1 review

Christopher Burke (West Midlands Genetics Laboratory)

Green List (high evidence)

ATP2B2 is associated with Deafness, autosomal dominant 82 (OMIM 619804) in OMIM. Emerging evidence suggests that heterozygous pathogenic variants in ATP2B2 can cause a neurodevelopmental phenotype.

Recent papers have outlined and extended neurodevelopmental phenotype (PMID: 39367743, PMID: 37675773, PMID: 29655659) not documented in OMIM or G2P. Summarised phenotypes from 14 reported individuals (13 unrelated individuals) - Global developmental delay (12/14), delayed motor development (12/14), ataxia (9/14), impaired speech (13/14), intellectual disability (13/14), cerebellar atrophy (4/14), behavioural issues (9/14), seizures (9/14), hypotonia (6/14), dysmorphic features (4/14), hearing abnormalities (3/14), and ophthalmological abnormalities (6/14).

PMID: 29655659 - Heterozygous missense. Targeted NGS, unknown inheritance.

PMID: 37675773 - Trio exome sequencing for families 1-6, confirmed de novo status for all 6 families. Seventh family could not be confirmed. 5 missense variants, 2 frameshift variants.

PMID: 39367743 - Trio exome sequencing for families 1-4, confirmed de novo in all 4 families. One case paternally inherited, one unknown. 4 missense variants, 1 frameshift variant (2 individuals in the same family).

ATP2B2 is plasma membrane Ca2+ ATPase involved in Ca2+ homeostasis. Ca2+ deregulation in humans and mice can cause cognitive, behavioural, sensory, and movement disorders. Discussed in detail in PMID: 37675773.

Request addition to R27, R29, R55, R59, R69, R84, Ataxia and Cerebellar Anomalies - Narrow Panel.
Sources: Expert Review
Created: 24 Jun 2026, 2:26 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global Developmental Delay; Delayed Motor Development; Ataxia; Impaired Speech; Intellectual Disability; Cerebellar Atrophy; Behavioural Issues; Seizures; Hypotonia; Dysmorphic Features; Hearing Abnormalities; Ophthalmological Abnormalities

Publications

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

Created: 24 Jun 2026, 2:26 p.m.

Panel version: 10.25

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Phenotypes

Global Developmental Delay
Delayed Motor Development
Ataxia
Impaired Speech
Intellectual Disability
Cerebellar Atrophy
Behavioural Issues
Seizures
Hypotonia
Dysmorphic Features
Hearing Abnormalities
Ophthalmological Abnormalities

OMIM

108733

Clinvar variants

Variants in ATP2B2

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

24 Jun 2026, Gel status: 0

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

Christopher Burke (West Midlands Genetics Laboratory)

gene: ATP2B2 was added gene: ATP2B2 was added to Intellectual disability. Sources: Expert Review Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATP2B2 were set to PMID: 29655659; 37675773; 39367743 Phenotypes for gene: ATP2B2 were set to Global Developmental Delay; Delayed Motor Development; Ataxia; Impaired Speech; Intellectual Disability; Cerebellar Atrophy; Behavioural Issues; Seizures; Hypotonia; Dysmorphic Features; Hearing Abnormalities; Ophthalmological Abnormalities Penetrance for gene: ATP2B2 were set to unknown Review for gene: ATP2B2 was set to GREEN gene: ATP2B2 was marked as current diagnostic

Intellectual disability Gene: ATP2B2