ABCC8
ATP binding cassette subfamily C member 8, the group of ATP binding cassette subfamily C
Basic information
Region (hg38): 11:17392498-17476894
Previous symbols: [ "SUR", "HRINS" ]
Links
Phenotypes
GenCC
Source:
- hyperinsulinemic hypoglycemia, familial, 1 (Definitive), mode of inheritance: AD
- familial hyperinsulinism (Definitive), mode of inheritance: AR
- hyperinsulinemic hypoglycemia, familial, 1 (Strong), mode of inheritance: AD
- diabetes mellitus, permanent neonatal 3 (Strong), mode of inheritance: AD
- hyperinsulinemic hypoglycemia, familial, 1 (Strong), mode of inheritance: AR
- diabetes mellitus, permanent neonatal 3 (Strong), mode of inheritance: AR
- transient neonatal diabetes mellitus (Strong), mode of inheritance: AD
- diabetes mellitus, noninsulin-dependent (Strong), mode of inheritance: AD
- diabetes mellitus, transient neonatal, 2 (Strong), mode of inheritance: Unknown
- hypoglycemia, leucine-induced (Strong), mode of inheritance: AD
- permanent neonatal diabetes mellitus (Strong), mode of inheritance: AR
- diabetes mellitus, permanent neonatal 3 (Definitive), mode of inheritance: Semidominant
- hyperinsulinemic hypoglycemia, familial, 1 (Definitive), mode of inheritance: Semidominant
- maturity-onset diabetes of the young (Supportive), mode of inheritance: AD
- DEND syndrome (Supportive), mode of inheritance: AD
- autosomal recessive hyperinsulinism due to SUR1 deficiency (Supportive), mode of inheritance: AR
- permanent neonatal diabetes mellitus (Supportive), mode of inheritance: AD
- transient neonatal diabetes mellitus (Supportive), mode of inheritance: AD
- autosomal dominant hyperinsulinism due to SUR1 deficiency (Supportive), mode of inheritance: AD
- diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency (Supportive), mode of inheritance: AD
- diabetes mellitus, transient neonatal, 2 (Strong), mode of inheritance: AD
- diabetes mellitus, permanent neonatal 3 (Strong), mode of inheritance: AR
- type 2 diabetes mellitus (Limited), mode of inheritance: AD
- hyperinsulinemic hypoglycemia, familial, 1 (Strong), mode of inheritance: AD
- hyperinsulinemic hypoglycemia, familial, 1 (Strong), mode of inheritance: AR
- pulmonary arterial hypertension (Moderate), mode of inheritance: AD
- monogenic diabetes (Definitive), mode of inheritance: Semidominant
- diabetes mellitus (Definitive), mode of inheritance: Semidominant
- hyperinsulinemic hypoglycemia, familial, 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Diabetes mellitus, transient neonatal, 2; Diabetes, permanent neonatal 3; Hyperinsulinemic hypoglycemia, familial, 1; Hypoglycemia, leucine-induced | AD/AR | Endocrine | Prompt treatment (eg, of ketoacidosis and dehydration) can avoid morbidity; Individuals with neonatal diabetes mellitus may respond well to sulfonylurea treatment; Non-neonatally affected individuals may respond to diazoxide; Individuals with leucine-induced hypoglycemia may have episodes triggered by high-protein (high leucine) feedings, and may respond to diazoxide | Endocrine | 7847376; 7716548; 923011; 8751851; 9727845; 10426386; 10322395; 11808881; 10334322; 1018078; 12559865; 12941782; 15356046; 15579781; 16885549; 16882742; 16613899; 8596924; 19254908; 20301620; 21716120; 23273570 |
| Hyperinsulinemic hypoglycemia, familial, 1 inheritance may involve imprinting |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (1983 variants)
- Hyperinsulinemic_hypoglycemia,_familial,_1 (724 variants)
- Type_2_diabetes_mellitus (485 variants)
- Diabetes_mellitus,_transient_neonatal,_2 (453 variants)
- Maturity_onset_diabetes_mellitus_in_young (451 variants)
- Transitory_neonatal_diabetes_mellitus (423 variants)
- Diabetes_mellitus,_permanent_neonatal_3 (376 variants)
- Leucine-induced_hypoglycemia (371 variants)
- Hereditary_hyperinsulinism (314 variants)
- not_specified (272 variants)
- Inborn_genetic_diseases (172 variants)
- Permanent_neonatal_diabetes_mellitus (128 variants)
- ABCC8-related_disorder (102 variants)
- Familial_hyperinsulinism (64 variants)
- Neonatal_diabetes_mellitus (38 variants)
- Monogenic_diabetes (18 variants)
- Pulmonary_arterial_hypertension (12 variants)
- Hypoglycemia (5 variants)
- MATURITY-ONSET_DIABETES_OF_THE_YOUNG,_TYPE_12 (4 variants)
- See_cases (3 variants)
- Hyperinsulinism,_Dominant/Recessive (3 variants)
- Transient_Neonatal_Diabetes,_Dominant (3 variants)
- Macrotia (2 variants)
- Growth_delay (2 variants)
- Gastroesophageal_reflux (2 variants)
- Short_stature (2 variants)
- Macrocephaly (2 variants)
- Atrial_septal_defect (2 variants)
- Congestive_heart_failure (2 variants)
- Neonatal_respiratory_distress (2 variants)
- Cardiac_shunt (2 variants)
- Small_for_gestational_age (2 variants)
- Feeding_difficulties (2 variants)
- Hereditary_disease (1 variants)
- Neonatal_hypotonia (1 variants)
- Large_for_gestational_age (1 variants)
- Polyhydramnios (1 variants)
- Generalized_hypotonia (1 variants)
- Triangular_face (1 variants)
- Retrognathia (1 variants)
- Hyperinsulinemia (1 variants)
- Large_fleshy_ears (1 variants)
- Broad_forehead (1 variants)
- Bilateral_cryptorchidism (1 variants)
- Diabetes_mellitus (1 variants)
- Congenital_isolated_hyperinsulinism (1 variants)
- Pointed_chin (1 variants)
- Autosomal_dominant_hyperinsulinism_due_to_SUR1_deficiency (1 variants)
- Long_philtrum (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCC8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000352.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 37 | 806 | 849 | |||
| missense | 33 | 166 | 627 | 38 | 864 | |
| nonsense | 55 | 48 | 104 | |||
| start loss | 3 | 2 | 5 | |||
| frameshift | 58 | 88 | 12 | 158 | ||
| splice donor/acceptor (+/-2bp) | 17 | 78 | 20 | 115 | ||
| Total | 166 | 386 | 697 | 844 | 2 |
Highest pathogenic variant AF is 0.0001846173
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ABCC8 | protein_coding | protein_coding | ENST00000389817 | 39 | 84018 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 7.96e-24 | 0.999 | 125632 | 0 | 116 | 125748 | 0.000461 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.91 | 752 | 915 | 0.822 | 0.0000593 | 10229 |
| Missense in Polyphen | 159 | 231.98 | 0.68541 | 2681 | ||
| Synonymous | -0.853 | 409 | 388 | 1.06 | 0.0000268 | 3228 |
| Loss of Function | 3.35 | 51 | 84.2 | 0.606 | 0.00000456 | 892 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000785 | 0.000771 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.000386 | 0.000326 |
| Finnish | 0.000238 | 0.000231 |
| European (Non-Finnish) | 0.000557 | 0.000554 |
| Middle Eastern | 0.000386 | 0.000326 |
| South Asian | 0.000591 | 0.000588 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- 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}.;
- Disease
- DISEASE: Leucine-induced hypoglycemia (LIH) [MIM:240800]: Rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglycemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine. {ECO:0000269|PubMed:15356046}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Familial hyperinsulinemic hypoglycemia 1 (HHF1) [MIM:256450]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. {ECO:0000269|PubMed:10202168, ECO:0000269|PubMed:10334322, ECO:0000269|PubMed:10615958, ECO:0000269|PubMed:11018078, ECO:0000269|PubMed:11226335, ECO:0000269|PubMed:11867634, ECO:0000269|PubMed:12364426, ECO:0000269|PubMed:12941782, ECO:0000269|PubMed:15562009, ECO:0000269|PubMed:15579781, ECO:0000269|PubMed:15807877, ECO:0000269|PubMed:16357843, ECO:0000269|PubMed:16429405, ECO:0000269|PubMed:24814349, ECO:0000269|PubMed:25720052, ECO:0000269|PubMed:8650576, ECO:0000269|PubMed:8751851, ECO:0000269|PubMed:8923011, ECO:0000269|PubMed:9618169, ECO:0000269|PubMed:9648840, ECO:0000269|PubMed:9769320}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, permanent neonatal (PNDM) [MIM:606176]: A rare form of diabetes distinct from childhood- onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy. {ECO:0000269|PubMed:16613899, ECO:0000269|PubMed:16885549, ECO:0000269|PubMed:17213273, ECO:0000269|PubMed:17668386}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Transient neonatal diabetes mellitus 2 (TNDM2) [MIM:610374]: Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first months of life. Transient neonatal diabetes remits early, with a possible relapse during adolescence. {ECO:0000269|PubMed:16885549}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Type II diabetes mellitus - Homo sapiens (human);ABC transporters - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Glibenclamide Action Pathway;Gliclazide Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Pancreas Function;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Repaglinide Action Pathway;Nateglinide Action Pathway;Defective ABCC8 can cause hypoglycemias and hyperglycemias;Disorders of transmembrane transporters;Disease;Metabolism;Regulation of insulin secretion;Neuronal System;ATP sensitive Potassium channels;Integration of energy metabolism;ABC transporter disorders;Inwardly rectifying K+ channels;Potassium Channels;FOXA2 and FOXA3 transcription factor networks
(Consensus)
Recessive Scores
- pRec
- 0.435
Intolerance Scores
- loftool
- 0.0423
- rvis_EVS
- -2.09
- rvis_percentile_EVS
- 1.57
Haploinsufficiency Scores
- pHI
- 0.150
- hipred
- Y
- hipred_score
- 0.771
- ghis
- 0.635
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.718
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Abcc8
- Phenotype
- endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- cellular glucose homeostasis;potassium ion transport;female pregnancy;memory;visual learning;response to pH;response to zinc ion;negative regulation of low-density lipoprotein particle clearance;negative regulation of angiogenesis;response to lipopolysaccharide;positive regulation of tumor necrosis factor production;response to insulin;response to drug;negative regulation of insulin secretion;regulation of insulin secretion;transmembrane transport;negative regulation of glial cell proliferation;negative regulation of wound healing;negative regulation of neuroblast migration;cellular response to organic substance;potassium ion transmembrane transport;positive regulation of uterine smooth muscle relaxation;positive regulation of voltage-gated potassium channel activity;positive regulation of tight junction disassembly;negative regulation of maintenance of permeability of blood-brain barrier
- Cellular component
- mitochondrion;plasma membrane;inward rectifying potassium channel;membrane;synaptic vesicle membrane;sarcolemma
- Molecular function
- potassium channel activity;ATP binding;sulfonylurea receptor activity;ATP-activated inward rectifier potassium channel activity;ATPase activity, coupled to transmembrane movement of substances;ion channel binding