Gastrointestinal epithelial barrier disorders

Gene: ZAP70

Comment on list classification: One case study where a variant has been found in a patient with inflammatory colitis. Unable to find any more case studies to support the gene-disease relationship. Given this evidence and the expert review, I have promoted this gene to amber.

Created: 26 Jul 2018, 1:40 p.m.

Comment on list classification: Rated green by expert review, and found in all 4 original sources. Although currently only one family (2 siblings) reported in the literature at present (PMID: 26783323) for the association with infantile autoimmune disorder, there are many functional and other clinical studies to provide evidence that certian variants within ZAP70 that result in activation lead to autoimmunity/inflammatory responses. Most cases reported are in patients with immunodeficiency, and evidence is strong for this association, providing support that if deficiency of the ZAP70 transcription factor can lead to immunodeficiency, upregulation of ZAP70 could result in autoimmunity/inflammatory responses.

Created: 12 Oct 2016, 8:11 a.m.

Comment on mode of pathogenicity: Hypomorphic and activating variants in ZAP70 result in autoimmune/inflammatory responses, whereas loss-of-function variants (ZAP70 deficiency) result in immunodeficiency.

Created: 12 Oct 2016, 8:02 a.m.

Green List (high evidence)

Red List (low evidence)

Associated with phenotype in OMIM, not in G2P / DD. Present on UKGTN Very Early Onset Inflammatory Bowel Disease 40 Gene Panel. Two variants reported as compound heterozygotes in one family

Created: 6 Sep 2016, 11:27 a.m.

Comment on phenotypes: Variants also reported in Immunodeficiency 48 269840

Created: 6 Sep 2016, 11:25 a.m.