Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: ANKZF1
Comment on list classification: AS there is sufficient evidence for the association of monoallelic variants with infantile-onset inflammatory bowel disease, this gene can be promoted to green rating in the next GMS review.Created: 14 Feb 2024, 3:04 p.m. | Last Modified: 14 Feb 2024, 3:04 p.m.
Panel Version: 4.175
Comment on mode of inheritance: There are three unrelated cases reported with monoallelic ANKZF1 variants and infantile-onset inflammatory bowel disease. However, there are only two unrelated cases reported with biallelic variants, of which one has homozygous variant and other has compound heterozygous variants. The homozygous variant (p.Arg585Gln) is very common in gnomAD. Functional studies show that R585Q variant causes reduced ANKZF1 mRNA and protein expression and leads to reduced stress-induced mitochondrial translocation.
The MOI should therefore be set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" with the current evidence. In addition, 'watchlist_moi' tag has been added to review any new evidence in support of the association of biallelic variants to inflammatory bowel disease.Created: 14 Feb 2024, 3 p.m. | Last Modified: 14 Feb 2024, 3:02 p.m.
Panel Version: 4.174
Comment on phenotypes: This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.Created: 14 Feb 2024, 2:48 p.m. | Last Modified: 14 Feb 2024, 2:48 p.m.
Panel Version: 4.172
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
inflammatory bowel disease, MONDO:0005265
Publications
PMID: 28302725 (2017) identified two infantile-onset IBD patients with biallelic ANKZF1 variants + some functional work:
One homozygous for R585Q - although this variant is very common in gnomAD
One compound heterozygous for E152K and V32_Q87del
Also two patients with one heterozygous variants
PMID: 36857589 (2023) also identified a de novo variant (p.Leu415Val) in a young patient with IBD
Sources: LiteratureCreated: 12 Feb 2024, 4:53 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Inflammatory bowel disease
Publications
Gene: ankzf1 has been classified as Amber List (Moderate Evidence).
Tag watchlist_moi tag was added to gene: ANKZF1.
Mode of inheritance for gene: ANKZF1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANKZF1 were set to PMID: 28302725; PMID: 36857589
Phenotypes for gene: ANKZF1 were changed from Inflammatory bowel disease to inflammatory bowel disease, MONDO:0005265
Tag Q1_24_promote_green tag was added to gene: ANKZF1. Tag Q1_24_NHS_review tag was added to gene: ANKZF1.
gene: ANKZF1 was added gene: ANKZF1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: ANKZF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ANKZF1 were set to PMID: 28302725; PMID: 36857589 Phenotypes for gene: ANKZF1 were set to Inflammatory bowel disease Review for gene: ANKZF1 was set to AMBER