Atypical haemolytic uraemic syndrome

Gene: THBD

Red List (low evidence)

THBD (thrombomodulin)
EnsemblGeneIds (GRCh38): ENSG00000178726
EnsemblGeneIds (GRCh37): ENSG00000178726
OMIM: 188040, Gene2Phenotype
THBD is in 8 panels

6 reviews

David Kavanagh (Newcastle upon Tyne NHS hospitals trust)

Red List (low evidence)

Initially linked to aHUS in N Engl J Med. 2009 Jul 23;361(4):345-57.
Subsequent studies have failed to validate association: J Am Soc Nephrol. 2018 Dec;29(12):2809-2819; J Immunol. 2018 Apr 1;200(7):2464-2478; Clin J Am Soc Nephrol. 2013 Apr;8(4):554-62
Created: 6 Aug 2019, 9:20 a.m. | Last Modified: 6 Aug 2019, 9:20 a.m.
Panel Version: 1.9

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Thrombophilia due to thrombomodulin defect MIM614486; aHUS MIMN 612926

Publications

Eleanor Williams (Genomics England Curator)

I don't know

THBD was discussed with the NHS GMS renal specialist group on 2019-02-04. It was decided that this gene should remain red on the panel.
Created: 12 Feb 2019, 12:44 p.m.
This gene was part of an initial gene list collated by Valerie Wilson, The National Renal Complement Therapeutics Centre, February 2019 on behalf of Yorkshire and North East GLH for the GMS Renal Specialist Test Group; Gene Symbol submitted: THBD; Suggested initial gene rating: none provided;
Created: 12 Feb 2019, 12:40 p.m.

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

A literature search did not result in further evidence of an association between THBD and and Atypical haemolytic uraemic syndrome. In addition, Osborne et al 2018 (29500241) performed analysis of 610 rare genetic variants from 6 centres in 13 genes including THBD from >3500 patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. After comparing allele frequencies of variants in these genes with those found in the ExAC server, no association was found between the rare variants in THBD and aHUS.
Created: 5 Jul 2018, 1:24 p.m.

Tim Goodship (Newcastle University)

Red List (low evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Variants in this GENE are reported as part of current diagnostic practice

Daniel Gale (UCL)

Red List (low evidence)

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P. At least nine variants reported but multi-factorial influences prevent this gene from being made green at the moment
Created: 17 Aug 2016, 12:38 p.m.
Comment on list classification: THBD is controversial because there are reports of THBD variants in aHUS patients, however, it is not clear how strong their effects are. The low penetrance is seen in variants of other (established) aHUS genes, but causative variants in THBD have not been reported in the absence of other gene variants or external factors. Therefore, it may be that the presence of a THBD variant is neither necessary nor sufficient to cause aHUS (D. Gale personal communication)
Created: 17 Aug 2016, 12:35 p.m.
Nine disease associated variants reported in the literature (PMIDs 19625716, 25135378, 20513133). Variants p.Ala43Thr and p.Asp53Gly (PMIDs 19625716) were reported in unaffected family members of the probands, with the implication that those carriers had remained unaffected because they may not have been in contact with the triggering insult of a relevant bacterial or viral infection, or vaccination. Other THBD variants have also been reported with variants in CF1, CFHR5 and CFB genes (20513133, 23307876).
Created: 16 Aug 2016, 11:36 a.m.
Comment on phenotypes: Variants also reported in Thrombophilia due to thrombomodulin defect 614486
Created: 16 Aug 2016, 9:45 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • NHS GMS
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926
  • Thrombophilia due to thrombomodulin defect 614486
Tags
multifactorial
OMIM
188040
Clinvar variants
Variants in THBD
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

14 Aug 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: THBD were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926 to Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926; Thrombophilia due to thrombomodulin defect 614486

12 Feb 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to THBD.

17 Aug 2016, Gel status: 1

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted 17/08/2016

17 Aug 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

17 Aug 2016, Gel status: 1

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for THBD was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Aug 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

16 Aug 2016, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for THBD were set to 19625716; 25135378; 20513133; 23307876

16 Aug 2016, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for THBD were set to 19625716; 25135378; 20513133

16 Aug 2016, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for THBD were set to Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926

16 Aug 2016, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for THBD were set to Thrombophilia due to thrombomodulin defect, 614486; {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, 612926

29 Oct 2015, Gel status: 2

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

THBD was added to Atypical haemolytic uraemic syndromepanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene THBD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

29 Oct 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

THBD was created by ellenmcdonagh

29 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

THBD was added to Atypical haemolytic uraemic syndromepanel. Sources: Radboud University Medical Center, Nijmegen