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Intellectual disability

Gene: AP1G1

Amber List (moderate evidence)

AP1G1 (adaptor related protein complex 1 gamma 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000166747
EnsemblGeneIds (GRCh37): ENSG00000166747
OMIM: 603533, Gene2Phenotype
AP1G1 is in 2 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark. Usmani et al., 2021 (PMID: 34102099) identified 9 families with heterozygous and 2 families with homozygous variants in this gene. All individuals (12) had GDD and ID of various severity (mild to severe), except one patient who died at 22 days. Other features include hypotonia (9/10), seizures (6/10) and spasticity (4/10). Some supportive functional data included.

There is sufficient evidence to promote this gene to Green at the next GMS panel update, with 'monoallelic' MOI. Biallelic cases would still be picked up by the Genomics England pipeline - but this may be reviewed if additional cases are discovered.
Created: 21 Sep 2021, 1:17 p.m. | Last Modified: 21 Sep 2021, 1:17 p.m.
Panel Version: 3.1292

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.

GREEN for mono-allelic, AMBER for bi-allelic.
Sources: Literature
Created: 7 Aug 2021, 7:39 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
Phenotypes
  • Neurodevelopmental disorder (NDD)
  • Intellectual Disability
  • Epilepsy
Tags
Q3_21_rating
OMIM
603533
Clinvar variants
Variants in AP1G1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

21 Sep 2021, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene AP1G1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

21 Sep 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_rating tag was added to gene: AP1G1.

21 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ap1g1 has been classified as Amber List (Moderate Evidence).

7 Aug 2021, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: AP1G1 was added gene: AP1G1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: AP1G1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: AP1G1 were set to 34102099 Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy Review for gene: AP1G1 was set to GREEN gene: AP1G1 was marked as current diagnostic