Familial Hirschsprung Disease

Gene: NUP98

Amber List (moderate evidence)

NUP98 (nucleoporin 98)
EnsemblGeneIds (GRCh38): ENSG00000110713
EnsemblGeneIds (GRCh37): ENSG00000110713
OMIM: 601021, Gene2Phenotype
NUP98 is in 1 panel

3 reviews

Rebecca Foulger (Genomics England curator)

Added 'watchlist' tag alongside Amber rating.
Created: 3 Aug 2017, 2:38 p.m.
Comment on list classification: Updated rating from Red to Amber: NUP98 is on original expert list submitted by Alder Hey (Simon Kenny/Sumita Chhabra) and Erasmus groups (Prof. Hofstra's group). A 2017 zebrafish model (PMID:28274275) supports the association, but not yet 3 cases to be considered diagnostic grade.
Created: 3 Aug 2017, 2:37 p.m.
PMID:28274275 (Gui et al., 2017) performed de novo mutation (DNM) screening on 24 HSCR trios. They identified a NUP98 N1662S missense mutation, which is predicted as highly deleterious by Polyphen2. PMID:28274275 also shows animal model: NUP98 knockdown disrupted ENS development and caused a HSCR-like phenotype in zebrafish.
Created: 1 Jun 2017, 1:01 p.m.

Erwin Brosens (Erasmus MC)

I don't know

Mode of inheritance
Unknown

Sumita Chhabra (University of Liverpool / Alder Hey Children's Hospital)

animal model confirmation
Created: 8 May 2017, 10:36 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Alder Hey - Erasmus MC
Phenotypes
  • susceptibility to Hirschsprung disease
Tags
watchlist
OMIM
601021
Clinvar variants
Variants in NUP98
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

18 Oct 2017, Gel status: 2

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

18th October 2017: Revised and approved to Version 1.0 after expert and curator review. An expert list from Mr. Simon Kenny and Professor Robert Hofstra's groups (Alder Hey - Erasmus MC) formed the basis of the original panel. The expert list was then expanded based on a review of literature. Many of the literature genes remain red on the V1.0 panel as they were identified through association studies and/or they represent susceptibility/risk factors for Hirschsprung's disease (HSCR). Sumita Chhabra (Alder Hey) and Erwin Brosens (Erasmus) provided extensive feedback for genes on the panel, together with reviews from Merce Garcia-Barcelo.

3 Aug 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for NUP98 were set to 28274275

8 May 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

NUP98 was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC

8 May 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

NUP98 was created by rfoulger