Congenital hypothyroidism

Gene: NKX2-5

Amber List (moderate evidence)

NKX2-5 (NK2 homeobox 5)
EnsemblGeneIds (GRCh38): ENSG00000183072
EnsemblGeneIds (GRCh37): ENSG00000183072
OMIM: 600584, Gene2Phenotype
NKX2-5 is in 16 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Amber until further information is available. Comment from Helen Brittain: PMID:16418214 identify 4 cases from 241 cases, but all were inherited from an unaffected parent and one unaffected sibling also carried the mutation. The authors postulate polygenic inheritance.
Created: 14 Feb 2017, 5:35 p.m.
Comment on mode of pathogenicity: PMID:16418214 (Dentice et al., 2006) report a dominant negative mode of action for 3 NKX2-5 mutations in patients with thyroid dysgenesis,
Created: 13 Feb 2017, 5:01 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM and G2P.
Created: 13 Feb 2017, 4:56 p.m.
Confirmed DD-G2P gene for 'Hypothyroidism, congenital nongoitrous, 5 (MIM:225250)'.
Created: 13 Feb 2017, 4:55 p.m.

Nadia Schoenmakers (University of Cambridge)

Red List (low evidence)

Highly variable penetrance, ambiguity as to whether Nkx2-5 mutations alone cause CH.
Created: 11 Feb 2017, 12:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
thyrioid ectopy, thyroid agenesis, congenital heart disease

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
  • Other
Phenotypes
  • Hypothyroidism, congenital nongoitrous, 5, 225250
  • thyrioid ectopy, thyroid agenesis, congenital heart disease
OMIM
600584
Clinvar variants
Variants in NKX2-5
Penetrance
Incomplete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

22 Feb 2017, Gel status: 2

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

22 February 2017: Promoted to Version 1. Reviews were assessed, and panel was revised according to expert review and additional curation. After discussion with the reviewer and in-house clinicians, it was agreed to include the genes for 'combined pituitary hormone deficiency' (CPHD) on the panel, since patients can present with central hypothyroidism (CH). In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies.

14 Feb 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).

13 Feb 2017, Gel status: 1

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for NKX2-5 was changed to Other - please provide details in the comments

13 Feb 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for NKX2-5 were set to Hypothyroidism, congenital nongoitrous, 5, 225250; thyrioid ectopy, thyroid agenesis, congenital heart disease

13 Feb 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for NKX2-5 were set to 16418214

13 Feb 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for NKX2-5 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

23 Jan 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

NKX2-5 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Radboud University Medical Center, Nijmegen

23 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

NKX2-5 was created by rfoulger

23 Jan 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

NKX2-5 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Other