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Primary immunodeficiency

Gene: TRAF3

Red List (low evidence)

TRAF3 (TNF receptor associated factor 3)
EnsemblGeneIds (GRCh38): ENSG00000131323
EnsemblGeneIds (GRCh37): ENSG00000131323
OMIM: 601896, Gene2Phenotype
TRAF3 is in 3 panels

3 reviews

Sophie Hambleton (Newcastle University)

Red List (low evidence)

Single patient though strong circumstantial evidence of pathogenicity
Created: 29 Jun 2018, 3:51 p.m.

Publications

Eleanor Williams (Genomics England Curator)

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.

Louise Daugherty (Genomics England Curator)

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.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • IUIS Classification December 2019
  • Expert Review Red
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Herpes simplex encephalitis, susceptibility to, 3
  • Defects in Intrinsic and Innate Immunity
  • {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5},614849
  • Herpes simplex virus 1 encephalitis
  • Herpetic encephalitis (HSE)
  • Defects in intrinsic and innate immunity
OMIM
601896
Clinvar variants
Variants in TRAF3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Feb 2020, Gel status: 1

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Source IUIS Classification December 2019 was added to TRAF3. Added phenotypes Defects in intrinsic and innate immunity; Herpes simplex virus 1 encephalitis for gene: TRAF3 Publications for gene TRAF3 were updated from 20832341; 11296228; 24378539 to 24378539; 20832341; 32048120; 11296228; 32086639

12 Jul 2018, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

5 Jul 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: traf3 has been classified as Red List (Low Evidence).

5 Jul 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TRAF3 were set to {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5},614849; Herpes simplex encephalitis, susceptibility to, 3; Herpetic encephalitis (HSE); Herpes simplex virus 1 encephalitis; Defects in Intrinsic and Innate Immunity

5 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: TRAF3 were set to 20832341; 11296228; 24378539

5 Jul 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: traf3 has been classified as Red List (Low Evidence).

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TRAF3 were set to Herpes simplex encephalitis, susceptibility to, 3, Herpetic encephalitis (HSE), Herpes simplex virus 1 encephalitis, Defects in Intrinsic and Innate Immunity

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to TRAF3. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to TRAF3. Panel: Primary immunodeficiency disorders

19 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to TRAF3. Panel: Primary immunodeficiency disorders Phenotypes for gene TRAF3 were set to Herpes simplex encephalitis, susceptibility to, 3, Herpetic encephalitis (HSE)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TRAF3 were set to Herpes simplex encephalitis, susceptibility to, 3

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

TRAF3 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TRAF3 was created by Louise Daugherty