Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: ANKZF1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:34 p.m. | Last Modified: 26 Sep 2024, 3:34 p.m.

Panel Version: 6.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

ClinGen has classified this gene as 'No Known Disease Relationship' based on mode of inheritance is undertemined by the Primary Immune Regulatory Disorders expert panel (https://search.clinicalgenome.org/CCID:008790) However, they made the decision based on the evidence provided only from PMID:28302725. This publication reported two biallelic cases and two monoallelic cases. However, there was third monoallelic case reported in PMID:36857589.

This gene is also rated green for monoallelic MOI by PanelApp Australia on Inflammatory bowel disease panel (https://panelapp-aus.org/panels/123/gene/ANKZF1/)

This gene should therefore remain green on this panel.

Created: 16 Oct 2025, 10:34 a.m. | Last Modified: 16 Oct 2025, 10:34 a.m.

Panel Version: 8.47

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

• 28302725
• 36857589

I don't know

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: Literature

Created: 12 Feb 2024, 4:53 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Inflammatory bowel disease

Publications

• PMID: 28302725
• PMID: 36857589