ABCC8 |
- 30
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- ABCC8 (HGNC:59) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- ATP binding cassette subfamily C member 8
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- SUR, HRINS
- Alias symbols
- HI, PHHI, SUR1, MRP8, ABC36, HHF1, TNDM2
- %HI
- 1.79(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 0.77(Read more about gnomAD LOEUF score)
- Cytoband
- 11p15.1
- Genomic Coordinates
-
GRCh37/hg19: chr11:17414045-17498392 NCBI Ensembl UCSC GRCh38/hg38: chr11:17392498-17476845 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000352.6 ENST00000389817.8 (Read more about MANE Select)
- Function
- Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release. {ECO:0000269|PubMed:24814349, ECO:0000269|PubMed:25720052}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-17424
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Gene Associated with Autosomal Recessive Phenotype
(30)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
02/24/2012
Haploinsufficiency (HI) Score Details
HI Score:
30
HI Evidence Strength:
Gene Associated with Autosomal Recessive Phenotype
(Disclaimer)
HI Disease:
- hyperinsulinemic hypoglycemia, familial, 1 Monarch
HI Evidence Comments:
Familial hyperinsulinemia (http://www.ncbi.nlm.nih.gov/books/NBK1375) can be caused by homozygous loss of function mutations in ABCC8 and is typically diffuse pancreatic disease. A subset of cases are caused by paternally inherited heterozygous mutations that lead to focal disease due to somatic loss of heterozygosity, with penetrance of 1-2%. Loss of heterozygosity results in expression of this AR condition in a histologically focal manner. Flanagan (2011, PMID:21978130) reports 2 individuals with focal hyperinsulinemia with paternally inherited partial gene deletions. Affected pancreatic tissue was not available for confirmation of loss of heterozygosity. Damaj (2008, PMID: 18796520) reports 1 individual with focal hyperinsulinemia cause by a paternally inherited 5 basepair deletion in ABCC8 and subsequent somatic paternal isodisomy and loss of heterozygosity. Bellanne-Chantelot (2010, PMID:20685672) reports a large study of 37patients with focal hyperinsulinemia and review of previous studies. Multiple frameshift or truncating heterozygou mutations are reported. Of cases with complete parental information, 2 were de novo and the rest were paternal. Loss of heterozygosity in the affected tissue was documented for two patients.
Permanent neonatal diabetes mellitus (http://www.ncbi.nlm.nih.gov/books/NBK1447) can be caused by activating missense mutations in ABCC8 (with both dominant and recessive inheritance). Mutations lead to decreased sensitivity to channel inhibitors and subsequent increased cellular activity (Babenko, PMID: 16885549). Expression is variable and can include childhood or adult onset diabetes.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000011.9)
(NC_000011.10)