Newborns additional phenotypes panel 1
Gene: ABCC8EnsemblGeneIds (GRCh38): ENSG00000006071
EnsemblGeneIds (GRCh37): ENSG00000006071
OMIM: 600509, Gene2Phenotype
ABCC8 is in 11 panels
2 reviews
Arina Puzriakova (Genomics England Curator)
Special Consideration: Multiple phenotypes with same MOI included.
Additional Information: ABCC8 related hyperinsulinism (LOF) and ABCC8 related neonatal diabetes (GOF) both included.Created: 25 Sep 2024, 11:26 a.m. | Last Modified: 18 Nov 2025, 3:52 p.m.
Panel Version: 0.102
Special Consideration: Awareness.
Additional Information: AD MOI was excluded due to large numbers of heterozygous variants being prioritised requiring manual review.Created: 25 Sep 2024, 11:23 a.m. | Last Modified: 25 Sep 2024, 11:26 a.m.
Panel Version: 0.100
Mafalda Gomes (Genomics England Curator)
The mechanism of pathogenicity is gain-of-function (GOF).Created: 1 Jun 2023, 2:40 p.m. | Last Modified: 1 Jun 2023, 2:40 p.m.
Panel Version: 0.29
ABCC8 curation results (clinicalgenome.org)Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.
Panel Version: 0.26
The mechanism for dominant cases is activating variants resulting in a KATP channel unable to close in response to ATP, impairing insulin secretion. The occasional recessive cases are caused by either (1) homozygosity or compound heterozygosity for partially activating variants or (2) a partially activating variant that only causes diabetes when inherited in trans with an inactivating variant. So, seems like LOF is rare and only causes disease when a GOF variant is in trans. But just to confirm, do we not want LOF prioritisation for AR? -> DB: I have taken your comment and added to spreadsheet to discuss with specialistsCreated: 17 May 2023, 1:43 p.m. | Last Modified: 17 May 2023, 1:43 p.m.
Panel Version: 0.11
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- Phenotypes
-
- Diabetes mellitus, permanent neonatal 3, with or without neurologic features, autosomal recessive
- Tags
- OMIM
- 600509
- Clinvar variants
- Variants in ABCC8
- Penetrance
- None
- Mode of Pathogenicity
- Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
- Panels with this gene
-
- Pulmonary arterial hypertension
- Multi-organ autoimmune diabetes
- Intellectual disability
- Monogenic diabetes
- Ketotic hypoglycaemia
- Neonatal diabetes - small panel
- Familial diabetes
- Neonatal diabetes
- Fetal anomalies
- Diabetes with additional phenotypes suggestive of a monogenic aetiology
- Congenital hyperinsulinism
History Filter Activity
Added Tag
Arina Puzriakova (Genomics England Curator)Tag special_consideration tag was added to gene: ABCC8.
Set Phenotypes
Sarah Leigh (Genomics England Curator)Phenotypes for gene: ABCC8 were changed from Diabetes mellitus, permanent neonatal 3, with or without neurologic features to Diabetes mellitus, permanent neonatal 3, with or without neurologic features, autosomal recessive
Set Phenotypes
Mafalda Gomes (Genomics England Curator)Added phenotypes Diabetes mellitus, permanent neonatal 3, with or without neurologic features for gene: ABCC8
Set mode of inheritance, Set Phenotypes
Mafalda Gomes (Genomics England Curator)Mode of inheritance for gene ABCC8 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Diabetes mellitus, permanent neonatal 3, with or without neurologic features for gene: ABCC8
Removed Tag
Mafalda Gomes (Genomics England Curator)Tag GOF was removed from gene: ABCC8.
Added New Source, Set Phenotypes, Status Update
Mafalda Gomes (Genomics England Curator)Source Expert Review Green was added to ABCC8. Added phenotypes Diabetes mellitus, permanent neonatal 3, with or without neurologic features for gene: ABCC8 Rating Changed from No List (delete) to Green List (high evidence)
Added New Source, Status Update
Mafalda Gomes (Genomics England Curator)Source Expert Review Removed was added to ABCC8. Rating Changed from Green List (high evidence) to No List (delete)
Added Tag
Mafalda Gomes (Genomics England Curator)Tag GOF tag was added to gene: ABCC8.
Created, Added New Source, Set mode of inheritance, Set Phenotypes, Set mode of pathogenicity
Mafalda Gomes (Genomics England Curator)gene: ABCC8 was added gene: ABCC8 was added to Newborns additional phenotypes panel. Sources: Expert Review Green Mode of inheritance for gene: ABCC8 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Phenotypes for gene: ABCC8 were set to Diabetes mellitus, permanent neonatal 3, with or without neurologic features Mode of pathogenicity for gene: ABCC8 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments