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Mendeliome v2.0 CREB3L3 Gene migrated from ENSG00000060566 to ENSG00000060566 (gene set migration)
Mendeliome v1.4712 CREB3L3 Bryony Thompson Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694
Mendeliome v1.4711 CREB3L3 Bryony Thompson Classified gene: CREB3L3 as Green List (high evidence)
Mendeliome v1.4711 CREB3L3 Bryony Thompson Gene: creb3l3 has been classified as Green List (High Evidence).
Mendeliome v1.4710 CREB3L3 Bryony Thompson edited their review of gene: CREB3L3: Added comment: Recent studies expand the evidence base for CREB3L3. PMID 34491909 adds a cohort of ten unrelated adults with heterozygous loss‑of‑function or missense CREB3L3 variants who present with severe adult‑onset hypertriglyceridemia, detailed lipoprotein profiling, and mouse‑model rescue of the lipid phenotype. PMID 41099101 reports six additional heterozygous CREB3L3 carriers among patients with multifactorial chylomicronemia syndrome.; Changed rating: GREEN; Changed publications: 41099101, 34491909, 26427795; Changed phenotypes: hypertriglyceridemia, MONDO:0005347; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7774 CREB3L3 Zornitza Stark Marked gene: CREB3L3 as ready
Mendeliome v0.7774 CREB3L3 Zornitza Stark Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7774 CREB3L3 Zornitza Stark Phenotypes for gene: CREB3L3 were changed from Hyperlipidaemia; hypertriglyceridemia to Hypertriglyceridaemia-2, MIM#619324
Mendeliome v0.7773 CREB3L3 Zornitza Stark reviewed gene: CREB3L3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertriglyceridaemia-2, MIM#619324; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6108 CREB3L3 Bryony Thompson Classified gene: CREB3L3 as Amber List (moderate evidence)
Mendeliome v0.6108 CREB3L3 Bryony Thompson Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6107 CREB3L3 Bryony Thompson gene: CREB3L3 was added
gene: CREB3L3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CREB3L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694
Phenotypes for gene: CREB3L3 were set to Hyperlipidaemia; hypertriglyceridemia
Review for gene: CREB3L3 was set to AMBER
Added comment: PMID: 26427795 - a loss of function variant (c.359delG p.K120fsX20) was identified in 2 affected adult siblings and a 13 yo normotriglyceridemic daughter of one of the siblings.
PMID: 21666694 - Lipoprotein profiles of the families of 4 individuals with CREB3L3 nonsense mutations showed a significantly elevated mean plasma TG level in 11 mutation carriers compared with 5 non-carrier first-degree relatives (9.67 ± 4.70 vs. 1.66 ± 0.55 mM, P = 0.021, Wilcoxon test). 3 of those families have the same variant - Lys245GlufsTer130, which has 126 (281,946 alleles) hets in gnomAD v2.1.
PMID: 32580631 - case-control analysis of nonmonogenic severe hypertriglyceridemia cases (N=265) vs normolipidemic controls (N=477), identified 5 cases with LoF variants (3 of whom had the Lys245GlufsTer130 frameshift) and none in controls. OR 20.2 (95% CI 1.11–366.1) p = 0.002, adjusted p = 0.03.
The frequency of Lys245GlufsTer130 is higher than expected for a dominant disorder, but other loss of function variants have been identified. The gene may be associated with variable penetrance. There are multiple supporting null mouse models with hyperlipidaemia.
Sources: Expert list