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| Autoinflammatory Disorders v2.21 | TOM1 | Zornitza Stark Marked gene: TOM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory Disorders v2.21 | TOM1 | Zornitza Stark Gene: tom1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory Disorders v2.21 | TOM1 | Zornitza Stark Classified gene: TOM1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory Disorders v2.21 | TOM1 | Zornitza Stark Gene: tom1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory Disorders v2.20 | TOM1 |
Zornitza Stark gene: TOM1 was added gene: TOM1 was added to Autoinflammatory Disorders. Sources: Literature Mode of inheritance for gene: TOM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TOM1 were set to 31263572; 40936361; 33864888 Phenotypes for gene: TOM1 were set to Immunodeficiency 85 and autoimmunity MIM#619510 Review for gene: TOM1 was set to AMBER Added comment: PMID 31263572: Parent and child reported with onset of atopic eczema and recurrent respiratory infections in the first decade of life; autoimmune enteropathy with vomiting, diarrhoea, and poor overall growth. More variable features included autoimmune oligoarthritis, interstitial pneumonitis, and EBV viremia. Laboratory studies showed hypogammaglobulinaemia and abnormal T-cell function, consistent with a combined immunodeficiency. Missense variant in TOM1, with limited functional data. PMID: 33864888 reports a new unrelated patient to the previous family, a 2yo with congenital autoimmune enteropathy, exocrine pancreatic insufficiency, failure to thrive, hepatitis, atopic dermatitis, pityriasis alba, hypogammaglobulinemia, lymphopenia. Has a canonical splice variant c.267+2T>C which they have shown has 2 splicing outcomes; intron 4 retention leading to a stopgain, or cryptic donor splicing causing an in frame deletion of ~130 amino acids of the vesicular trafficking domain. PMID: 40936361 no new patients just more functional data on the originally reported missense Gly307Asp. Typically TOM1 binding to TOLLIP decreases the affinity of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns3P), increasing the commitment of both proteins to cargo trafficking. This variant was shown to reduce this inhibitory effect, and impair TOM1's ability to inhibit TOLLIP binding to PtdIns3P. Patient cells also displayed delayed autophagosome clearance and more robust phosphorylation of ERK1/2 and AKT. Sources: Literature |
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