ANKZF1

Inheritance Pattern: Unknown

Disease ID:MONDO:0005265

Submitter: ClinGen

*ANKZF1* was first reported in relation to undetermined mode of inheritance inflammatory bowel disease in 2017 (Van Haaften-Visser DY et al. PMID: 28302725). Van Haaften-Visser specifies in the publication that their version of IBD is infantile onset, however there is no current MONDO term for IO-IBD. Four missense and one deletion variant that have been reported in four probands in one publication (PMID: 28302725) are included in this curation. The probands all presented with symptoms within the first six months of life. The female proband’s symptoms include lymphopenia, gastric and oral ulcers, abnormal T-, NK-, and B- cell counts, decreased circulating antibody concentration, bloody diarrhea, and mucus in stool. The male proband's symptoms include pancolitis. Two of the probands are said to be diagnosed with IO-IBD, but do not have any symptoms noted in the paper. Minimal evidence for a causal role for *ANKZF1* in infantile-onset inflammatory bowel disease has been reported. Although this gene-disease relationship is supported by the female patient with *ANKZF1* mRNA and protein expression being reduced in a homozygous R585Q mutation. The other three probands were either heterozygous, or compound heterozygous with no functional evidence available to show expression. In summary, the evidence supporting the relationship between *ANKZF1* and an undetermined mode of inheritance for infantile onset inflammatory bowel disease been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role. This classification was approved by the ClinGen PIRD GCEP on the meeting date April 15th, 2025 (SOP Version 11).

Inheritance Pattern: AR

Disease ID:MONDO:0005265

Submitter: PanelApp Australia