Infantile enterocolitis & monogenic inflammatory bowel diseaseGene: ZAP70
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.
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.
14th Oct 2016: panel revised according to expert review, additional curation for evidence level and internal clinical review, and promoted to version 1.
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for ZAP70 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of pathogenicity for ZAP70 was changed to Other - please provide details in the comments
Publications for ZAP70 were set to 26783323; 23406209 (association with Crohn's disease in adults); evidence for a role in autoimmune disease if ZAP70 is disregulated 27571017 and 26903241; PMID: 27288531 hypomorphic mutant allele of ZAP70 in SKG mouse model, which, upon exposure to fungal Ags, predisposes the mice to a CD4(+) T cell-mediated autoimmune arthritis that closely resembles rheumatoid arthritis in humans
Publications for ZAP70 were set to 26783323; 23406209 (association with Crohn's disease in adults)
Phenotypes for ZAP70 were set to SCID; Autoimmune disease, multisystem, infantile-onset, 2 617006
ZAP70 was added to Infantile enterocolitis & monogenic inflammatory bowel diseasepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services
Phenotypes for gene ZAP70 were set to SCID; Autoimmune disease, multisystem, infantile-onset, 2 617006
ZAP70 was created by ellenmcdonagh
ZAP70 was added to Infantile enterocolitis & monogenic inflammatory bowel diseasepanel. Sources: Expert list