Intellectual disability
Gene: ASCC3

ASCC3 (activating signal cointegrator 1 complex subunit 3)
EnsemblGeneIds (GRCh38): ENSG00000112249
EnsemblGeneIds (GRCh37): ENSG00000112249
OMIM: 614217, Gene2Phenotype
ASCC3 is in 4 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.

Panel Version: 9.299

PMID: 39286456 (2024) - three additional unrelated families identified with biallelic variants in the ASCC3 gene. All affected individuals had developmental delay and muscle fatigue. Other features included intellectual disability, hypotonia, motor impairment, feeding difficulties, and proximal/truncal muscle weakness.

Review of all reported cases (21 individuals) to date showed clinical heterogeneity, however most patients did exhibit intellectual disability of varying severity which can be the main presenting feature. Overall this supports inclusion of this gene on the panel.
Created: 25 Mar 2025, 3:47 p.m. | Last Modified: 25 Mar 2025, 3:47 p.m.

Panel Version: 8.204

Comment on publications: PMID: 39286456 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 25 Mar 2025, 3:07 p.m. | Last Modified: 25 Mar 2025, 3:07 p.m.

Panel Version: 8.204

Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
Created: 3 Apr 2024, 11:25 a.m. | Last Modified: 3 Apr 2024, 11:25 a.m.

Panel Version: 5.515

Created: 3 Apr 2024, 11:25 a.m.
Last Modified: 3 Apr 2024, 11:25 a.m.
Panel version: 9.299

Ivone Leong (Genomics England Curator)

Comment on list classification: Promoted from Red to Amber. New publication (https://doi.org/10.1016/j.xhgg.2021.100024) describing 11 individuals from 7 unrelated families (1 family was originally described in PMID: 21937992 and had mild ID). Patients had phenotypes ranging from mild to severe developmental dealys. As ID is not the prominant phenotype, this gene has been given an Amber rating.
Created: 12 Jul 2021, 12:44 p.m. | Last Modified: 12 Jul 2021, 12:44 p.m.

Panel Version: 3.1170

Created: 12 Jul 2021, 12:44 p.m.
Last Modified: 12 Jul 2021, 12:44 p.m.
Panel version: 3.1170

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
AUTOSOMAL RECESSIVE MENTAL RETARDATION

Publications

21937992

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Sarah Leigh (Genomics England Curator)

Red List (low evidence)

Candidate gene variants found in 32 ID probands (13/28 potentially pathogenic), no additional information provided (pmid 26350204). Not associated with phenotype in OMIM, but is a possible G2P associated gene. At least 1 variant reported in on non-syndromic case
Created: 31 Oct 2017, 9:57 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 31 Oct 2017, 9:57 a.m.

Panel version: Imported from Intellectual disability update Oct 2017 panel version 0.5

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:03 a.m.

Panel version: 0.306

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Intellectual developmental disorder, autosomal recessive 81, OMIM:620700

OMIM

614217

Clinvar variants

Variants in ASCC3

Penetrance

Complete

Publications

Panels with this gene