Familial Hirschsprung Disease

Gene: NKX2-1

Amber List (moderate evidence)

NKX2-1 (NK2 homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000136352
EnsemblGeneIds (GRCh37): ENSG00000136352
OMIM: 600635, Gene2Phenotype
NKX2-1 is in 19 panels

2 reviews

Erwin Brosens (Erasmus MC)

Red List (low evidence)

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Amber after discussion with Helen Brittain: 1 red review. 3 variants reported in PMID:15548547 and PMID:17640327 but insufficient family tree/additional information in the papers to currently use this gene in tiering. Added 'watchlist' tag to collate further information.
Created: 28 Aug 2017, 9:21 a.m.
PMID:15548547 (2005) identified a Chinese patient with HSCR who was heterozygous for a gly322-to-ser (G322S) mutation in the TITF1 (NKX2-1) gene. The authors further analyzed TITF1/NKX2-1 (PMID:17640327, 2007) and identified a M3L mutation in 2 Australian HSCR patients.
Created: 5 Jun 2017, 3:10 p.m.

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

Hirschsprung disease


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.

28 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).

14 Aug 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for NKX2-1 were set to Hirschsprung disease; short-segment aganglionosis

5 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

NKX2-1 was added to Familial Hirschsprung Diseasepanel. Sources: Other

5 Jun 2017, Gel status: 0


Rebecca Foulger (Genomics England curator)

NKX2-1 was created by rfoulger