ABCC8: ATP Binding Cassette Subfamily C Member 8
Sulfonylurea Receptor 1 (SUR1) – Key Regulator of Insulin Secretion and Target in Congenital Hyperinsulinism and Neonatal Diabetes
Gene Information Card
| Symbol | ABCC8 |
|---|---|
| Full Name | ATP Binding Cassette Subfamily C Member 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.1 |
| NCBI Gene ID | 6833 ncbi.nlm.nih.gov/gene/6833 |
| Ensembl ID | ENSG00000006071 |
| UniProt ID | Q09428 |
| OMIM ID | 600509 |
| HGNC ID | 59 |
| Aliases | SUR1, SUR, ABC36, HI, PHHI, TNDM2, HHF1, HRINS, MODY12 |
Description
ABCC8 encodes the sulfonylurea receptor 1 (SUR1), a regulatory subunit of the ATP-sensitive potassium (KATP) channel in pancreatic beta-cells. SUR1, together with the pore-forming Kir6.2 subunit (KCNJ11), couples cellular metabolism to membrane potential and insulin secretion. Loss-of-function mutations cause congenital hyperinsulinism (persistent hypoglycemia), while gain-of-function mutations lead to neonatal diabetes mellitus or MODY12. ABCC8 is also expressed in brain and smooth muscle, where it modulates neuronal excitability and vascular tone.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital Hyperinsulinism (HHF1) | Loss-of-function mutations impair KATP channel opening, causing persistent membrane depolarization and unregulated insulin secretion. | ClinVar, OMIM #256450 |
| Neonatal Diabetes Mellitus (TNDM2/PNDM) | Gain-of-function mutations prevent channel closure, reducing insulin secretion. Transient or permanent forms. | ClinVar, OMIM #610374 |
| Maturity-Onset Diabetes of the Young 12 (MODY12) | Activating missense variants cause mild, dominantly inherited diabetes. | OMIM #616329 |
| Sulfonylurea Drug Response | ABCC8 variants influence sensitivity to sulfonylureas used in diabetes therapy. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 58.2 | High |
| Brain | 12.4 | Medium |
| Heart | 6.8 | Low |
| Liver | 1.2 | Not detected |
| Skeletal Muscle | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta-cell) | — | High expression; used for KATP studies |
| MIN6 (mouse beta-cell) | — | High expression; insulin secretion model |
| HeLa | — | Low/absent; not endogenous |
| SH-SY5Y (neuroblastoma) | — | Moderate; neuronal SUR1 expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3992G>A (p.Arg1331Gln) | Missense | Common in HI | Loss-of-function; reduces ATP sensitivity |
| c.4552C>T (p.Arg1518Trp) | Missense | Rare | Gain-of-function; neonatal diabetes |
| c.1379G>A (p.Arg460His) | Missense | Found in MODY12 | Activating; mild diabetes |
| c.2011_2012delCT (p.Leu671fs) | Frameshift | Rare | Loss-of-function; severe hyperinsulinism |
Mutation functional classification
Loss of Function (LOF)
Impaired KATP channel opening → persistent depolarization → unregulated insulin secretion → congenital hyperinsulinism. Recessive or dominant negative.
Gain of Function (GOF)
Increased KATP channel open probability → hyperpolarization → reduced insulin secretion → neonatal diabetes or MODY. Dominant.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg1331Gln) can exert dominant-negative effects on channel function, causing hyperinsulinism in heterozygotes.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • ATPase activity |
| • sulfonylurea receptor activity | • ATP-sensitive potassium channel activity |
| • response to glucose | • insulin secretion |
| • regulation of membrane potential | • transmembrane transport |
Pathways
• KATP channel complex (Reactome: R-HSA-1296025)
• Regulation of insulin secretion (KEGG: hsa04911)
• Maturity onset diabetes of the young (KEGG: hsa04950)
Protein Summary
SUR1 (ABCC8) is a 1581-amino acid transmembrane protein with two nucleotide-binding domains (NBD1, NBD2) and multiple membrane-spanning helices. It functions as the regulatory subunit of the KATP channel, binding ATP/ADP and sulfonylurea drugs. Mutations in NBDs or transmembrane domains alter channel gating, leading to metabolic disorders. SUR1 is also a target for therapeutic sulfonylureas in diabetes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABCC8 Knockout HEK293 Cell Line | EDJ-KQ11943 | Human | 6833 | Details Get a Quote |
| ABCC8 Knockout A-549 Cell Line | EDJ-KQ40456 | Human | 6833 | Details Get a Quote |
| ABCC8 Knockout HeLa Cell Line | EDJ-KQ54591 | Human | 6833 | Details Get a Quote |
| ABCC8 Knockout HCT 116 Cell Line | EDJ-KQ71549 | Human | 6833 | Details Get a Quote |
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