Familial hypercholesterolaemia

Gene: APOB

Green List (high evidence)

APOB (apolipoprotein B)
EnsemblGeneIds (GRCh38): ENSG00000084674
EnsemblGeneIds (GRCh37): ENSG00000084674
OMIM: 107730, Gene2Phenotype
APOB is in 10 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 blood
Created: 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)

Green List (high evidence)

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)

Green List (high evidence)

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 cholesterol
Created: 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
  • 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
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

History Filter Activity

28 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

28 Jun 2016, Gel status: 4

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

28 Jun 2016, Gel status: 4

Set Mode of Inheritance

Ellen Thomas (Genomics England Curator)

Mode of inheritance for APOB was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

7 Oct 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

APOB was added to Familial hypercholesterolaemiapanel. Source: UKGTN

7 Oct 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

APOB was added to Familial hypercholesterolaemiapanel. Source: Emory Genetics Laboratory

7 Oct 2015, Gel status: 2

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

7 Oct 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

APOB was added to Familial hypercholesterolaemiapanel. Source: Illumina TruGenome Clinical Sequencing Services

7 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

APOB was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen

7 Oct 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

APOB was added to Familial hypercholesterolaemiapanel. Source: Eligibility statement prior genetic testing

7 Oct 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

APOB was added to Familial hypercholesterolaemiapanel. Sources: Eligibility statement prior genetic testing