Intellectual disability
Gene: WAPL

WAPL (WAPL cohesin release factor)
EnsemblGeneIds (GRCh38): ENSG00000062650
EnsemblGeneIds (GRCh37): ENSG00000062650
OMIM: 610754, Gene2Phenotype
WAPL is in 1 panel

1 review

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As there is sufficient evidence available for the association of WAPL gene with intellectual disability/ global developmental delay, this gene can be promoted to green rating in the next GMS update.
Created: 27 Jul 2026, 10:16 a.m. | Last Modified: 27 Jul 2026, 10:16 a.m.

Panel Version: 10.64

PMID:42431198 (2026) reported the identification of heterozygous WAPL variants in 27 patients, of which 19 patients had confirmed de novo variants. The WAPL-related disorder was characterised by developmental delay, intellectual disability, and risk of other developmental anomalies. Syndromic intellectual disability was reported in 6 patients and Global developmental delay (GDD) was reported in 10 patients.

Transcriptomics identified significant overlap between WAPL haploinsufficiency and 10q deletion differentially expressed genes. Mice with 50% Wapl expression exhibited mild deficits of growth and learning/memory, whereas those with 25% residual Wapl displayed birth defects and postnatal lethality, revealing a dosage liability threshold below the level of heterozygosity.

This gene has not yet been associated with relevant phenotypes in OMIM, Gene2Phenotype or ClinGen, but associated with green rating on the intellectual disability panel of PanelApp Australia.
Sources: Literature
Created: 27 Jul 2026, 10:12 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
complex neurodevelopmental disorder, MONDO:0100038

Publications

42431198

Created: 27 Jul 2026, 10:12 a.m.

Panel version: 10.63

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Amber
Literature

Phenotypes

complex neurodevelopmental disorder, MONDO:0100038

Tags

Q3_26_promote_green

OMIM

610754

Clinvar variants

Variants in WAPL

Penetrance

None

Publications

42431198

Panels with this gene

Intellectual disability

History Filter Activity

27 Jul 2026, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

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

27 Jul 2026, Gel status: 1

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

Achchuthan Shanmugasundram (Genomics England Curator)

gene: WAPL was added gene: WAPL was added to Intellectual disability. Sources: Literature Q3_26_promote_green tags were added to gene: WAPL. Mode of inheritance for gene: WAPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WAPL were set to 42431198 Phenotypes for gene: WAPL were set to complex neurodevelopmental disorder, MONDO:0100038 Review for gene: WAPL was set to GREEN

Intellectual disability Gene: WAPL