Familial hypercholesterolaemia
Gene: APOBEnsemblGeneIds (GRCh38): ENSG00000084674
EnsemblGeneIds (GRCh37): ENSG00000084674
OMIM: 107730, Gene2Phenotype
APOB is in 9 panels
5 reviews
Sarah Leigh (Genomics England Curator)
For FH
• Monoallelic
• Mostly missense variants
• Terminating variants unlikely to be involved
• Prevents the LDL particle from binding with cell surface receptors (LDLR)
• Increased levels of cholesterol in bloodCreated: 30 Sep 2019, 3:59 p.m. | Last Modified: 30 Sep 2019, 3:59 p.m.
Panel Version: 1.25
Ellen Thomas (Genomics England Curator)
Comment on mode of pathogenicity: Limited list of missense variants (only 1 or 2)Created: 28 Jun 2016, 12:26 p.m.
Ellen McDonagh (Genomics England Curator)
On the Inherited Cardiac Condition Genes panel for Familial Hypercholesterolaemia reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.1007/s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 35.Created: 19 Feb 2016, 2:47 p.m.
Ellen Thomas (Genomics England)
Loss-of-function variants cause low cholesterol - not relevant for this phenotype.
Only 1 or 2 mutations cause FH: R3527Q/W and possibly a milder phenotype with R3558C (although this is disputed and may be lower penetrance).Created: 2 Dec 2015, 10:05 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
steve Humphries (UCL)
in the UK about 5% of patients with monogenic FH have one particular mutation in the APOB gene which is p.(R3527Q)Created: 24 Nov 2015, 4:45 p.m.
truncation mutations cause hypoapoB and low levels of LDL and total cholesterolCreated: 24 Nov 2015, 4:34 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hypercholesterolaemia; elevated LDL-Cholesterol
Publications
- Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolaemia. Myant NB. Atherosclerosis. 1993 Dec
- 104(1-2):1-18. (8141833)
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Green
- UKGTN
- Emory Genetics Laboratory
- Illumina TruGenome Clinical Sequencing Services
- Radboud University Medical Center, Nijmegen
- Eligibility statement prior genetic testing
- Phenotypes
-
- Hypercholesterolemia, familial, 2, OMIM:144010
- OMIM
- 107730
- Clinvar variants
- Variants in APOB
- Penetrance
- Complete
- Publications
- 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
-
- Familial chylomicronaemia syndrome (FCS)
- Childhood onset dystonia, chorea or related movement disorder
- Likely inborn error of metabolism
- Familial hypercholesterolaemia
- Additional findings health related - children
- Intestinal failure or congenital diarrhoea
- Additional findings health related
- Familial hypercholesterolaemia (GMS)
- Undiagnosed metabolic disorders
History Filter Activity
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: APOB were changed from Gene part of the Global Lipid Genetic Consortium 12-SNP LDL-C gene score calculation (Talmud et al, 2013); Gene part of the 6-SNP LDL-C gene score calculation (Futema et al, 2015); Ag linked Hypobetalipoproteinemia; Hypobetalipoproteinemia, normotriglyceridemic; Hypercholesterolemia, due to ligand-defective apo B, 144010; Familial Hypercholesterolemia; Hypercholesterolemia; Familial Hypercholesterolaemia to Hypercholesterolemia, familial, 2, OMIM:144010
Gene classified by Genomics England curator
Ellen Thomas (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set mode of pathogenicity
Ellen Thomas (Genomics England Curator)Mode of pathogenicity for APOB was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Set Mode of Inheritance
Ellen Thomas (Genomics England Curator)Mode of inheritance for APOB was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added New Source
Ellen McDonagh (Genomics England Curator)APOB was added to Familial hypercholesterolaemiapanel. Source: UKGTN
Added New Source
Ellen McDonagh (Genomics England Curator)APOB was added to Familial hypercholesterolaemiapanel. Source: Emory Genetics Laboratory
Set Mode of Inheritance
Ellen McDonagh (Genomics England Curator)Model of inheritance for gene APOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added New Source
Ellen McDonagh (Genomics England Curator)APOB was added to Familial hypercholesterolaemiapanel. Source: Illumina TruGenome Clinical Sequencing Services
Added New Source
Ellen McDonagh (Genomics England Curator)APOB was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen
Added New Source
Ellen McDonagh (Genomics England Curator)APOB was added to Familial hypercholesterolaemiapanel. Source: Eligibility statement prior genetic testing
Added New Source
Ellen McDonagh (Genomics England Curator)APOB was added to Familial hypercholesterolaemiapanel. Sources: Eligibility statement prior genetic testing