COVID-19 research

Gene: TRAF3

Red List (low evidence)

Single patient though strong circumstantial evidence of pathogenicity

Created: 29 Jun 2018, 3:51 p.m.

Publications

• 20832341

Red List (low evidence)

In OMIM TRAF3 is provisionally associated with {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5}. Evidence cited in OMIM comes from Perez de Diego et al. (2010) (PMID: 20832341) who report a 18-year-old French female who had suffered from herpes simplex encephalitis (HSE) with a de novo missense change in TRAF3 (R118W). The analysis of patient's cells showed normal levels of TRAF3 mRNA, but severely reduced levels of TRAF3 protein. Expression of wildtype and mutant alleles in cell lines showed that the mutant was dominant-negative. Mikula et al. (2001)(PMID: 11296228) reported that mice lacking Craf1(TRAF3) died at mid gestation with placenta and liver anomalies. Chang et al. (2014)(PMID: 24378539) created mice deficient in Traf3 specifically in regulatory T (Treg) cells and concluded that TRAF3 is a signaling factor that mediates the effector functions of Treg cells, and is involved in induction of ICOS as a result of impaired ERK activation. No further evidence for association with from Gene2Phenotype or a search in PubMed.

Created: 27 Jun 2018, 9:26 a.m.

I don't know

Comment on publications: added publication to support gene-disease association

Created: 5 Jul 2018, 2:44 p.m.

Comment on list classification: Changed from Amber to Red until more info to support gene-disease association. Currently only one case reported in literature. Gene not present on any other PID related panels or within ESID or IUIS classifications. Request evidences /
immunological association of this gene from Victorian Clinical Genetics Services and GRID

Created: 5 Jul 2018, 2:43 p.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TRAF3 .PanelApp HGNC gene symbol check: TRAF3 . IUIS Disease: TRAF3 deficiency . IUIS Inheritance: AD .T cells: Normal or Increased activated T cells; low/normal iNK T cells, .B cells: N/A, .IUIS Other affected cells: CNS resident cells and fibroblasts. IUIS Associated features: Herpes simplex virus 1 encephalitis. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Herpes Simplex Encephalitis (HSE)

Created: 2 Jul 2018, 10:35 a.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s)
GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 19 Apr 2018, 11:28 a.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: TRAF3, PanelApp HGNC gene symbol check: TRAF3, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Herpetic encephalitis / Herpetic encephalitis (HSE)

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TRAF3, GRID_Gene_Symbol: TRAF3, GRID_Transcript_ENS_Community submitted: ENST00000560371, GRID_Transcript_RefSeq: NM_145725.2, GRID_Transcript_ENS_used_on_Production: ENST00000560371

Created: 17 Apr 2018, 12:12 p.m.