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Mendeliome

Gene: APOA4

Green List (high evidence)

APOA4 (apolipoprotein A4)
EnsemblGeneIds (GRCh38): ENSG00000110244
EnsemblGeneIds (GRCh37): ENSG00000110244
OMIM: 107690, Gene2Phenotype
APOA4 is in 2 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

5 families with autosomal dominant medullary amyloidosis. WGS/WES identified 2 different variants in the APOA4 gene (p.D33N in 3 families and p.L66V in 2 families). The variants were absent in gnomAD, located at the structurally flexible N-terminal domain of APOA4, and segregated with disease. There were 48 genotype +ve individuals with 44/48 having an eGFR <60. All clinically affected individuals presented with a bland urinary sediment, CKD, and no clinical evidence of systemic amyloidosis. Mean age of dialysis/transplantation was 58+/-11yrs. Routine kidney biopsies limited to the kidney cortex showed tubulointerstitial fibrosis and secondary glomerulosclerosis and no amyloid deposition. Four affected individuals were shown to have isolated medullary deposition of amyloid, with mass spectrometry showing the mutated Apoa4 as the primary constituent in 3 available cases. Plasma total ApoA4 levels were increased for patients (n=15) with ApoA4 mutations versus controls (n=49). They hypothesize that the amino acid substitutions alter the tertiary or quaternary structure of the mutated ApoA4, leading to increased plasma and primary urine concentrations and isolated medullary amyloid deposition.
Sources: Literature
Created: 11 Nov 2024, 5:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hereditary amyloidosis, MONDO:0018634, APOA4-related; Tubulointerstitial kidney disease, autosomal dominant 6, MIM# 621106

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Hereditary amyloidosis, MONDO:0018634, APOA4-related
  • Tubulointerstitial kidney disease, autosomal dominant 6, MIM# 621106
OMIM
107690
Clinvar variants
Variants in APOA4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Feb 2025, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: APOA4 were changed from Hereditary amyloidosis, MONDO:0018634, APOA4-related to Hereditary amyloidosis, MONDO:0018634, APOA4-related; Tubulointerstitial kidney disease, autosomal dominant 6, MIM# 621106

11 Nov 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: apoa4 has been classified as Green List (High Evidence).

11 Nov 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: apoa4 has been classified as Green List (High Evidence).

11 Nov 2024, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: APOA4 was added gene: APOA4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: APOA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: APOA4 were set to 38096951 Phenotypes for gene: APOA4 were set to Hereditary amyloidosis, MONDO:0018634, APOA4-related Review for gene: APOA4 was set to GREEN