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Intellectual disability

Gene: ATAD1

Amber List (moderate evidence)

ATAD1 (ATPase family, AAA domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000138138
EnsemblGeneIds (GRCh37): ENSG00000138138
OMIM: 614452, Gene2Phenotype
ATAD1 is in 4 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Multiple affected individuals from 3 unrelated families. There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 24 Jul 2020, 11:22 a.m. | Last Modified: 24 Jul 2020, 11:22 a.m.
Panel Version: 3.185
Not associated with any phenotype in G2P.

Pathogenic variants have been described in seven affected individuals (three distinct consanguineous families) including a homozygous nonsense (c.826G>T; p.Glu276*), frameshift (c.1070_1071delAT; p.His357Argfs*15), and missense (c.162G>C; p.Gln54His) variant in the ATAD1 gene. Patients present with severe neurological features of essentially total absence of psychomotor development, encephalopathy, extreme hypertonia, non-responsiveness to stimuli, and death within the first few months of life.

Knockout mouse model recapitulates phenotype. ATAD1 encodes Thorase, a mediator of AMPA receptor recycling; and therefore it was postulated that pathogenesis is a result of excessive AMPA receptor activity. Targeted therapy using perampanel, an AMPA receptor antagonist, ameliorated disease in both mice and humans, thus further supporting the role of ATAD1.
Created: 24 Jul 2020, 11:08 a.m. | Last Modified: 24 Jul 2020, 11:19 a.m.
Panel Version: 3.184

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy; Progressive hypertonia; Seizures

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Severe progressive neurological disorder, severe/profound intellectual disability is a feature
Sources: Expert list
Created: 29 Jan 2020, 8:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hyperekplexia 4, MIM#618011

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Hyperekplexia 4, MIM#618011
Tags
treatable for-review
OMIM
614452
Clinvar variants
Variants in ATAD1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Jul 2020, Gel status: 2

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag treatable tag was added to gene: ATAD1. Tag for-review tag was added to gene: ATAD1.

24 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: atad1 has been classified as Amber List (Moderate Evidence).

29 Jan 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: ATAD1 was added gene: ATAD1 was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: ATAD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATAD1 were set to 28180185 Phenotypes for gene: ATAD1 were set to Hyperekplexia 4, MIM#618011 Review for gene: ATAD1 was set to GREEN