Laterality disorders and isomerismGene: NKX2-5
This gene is associated with a phenotype in OMIM and Gene2Phenotype.
PMID: 12414819 describes 2 unrelated families. Family 1: 4 family members with variant in NKX2-5 had atrial septum defect. One of these family members was also diagnosed with polyspenia, midline symmetrical liver, ascending colon and caecum were shifted to the midline and forwards with the small intestine on the left. Family 2: 3 affected family members had atrial septum defect.
PMID: 25118008 describes a proband with a frameshift variant in NKX2-5 with the following phenotypes: double outlet right ventricle, common AV canal, total anomalous pulmonary venous connection, asplenia, failure to thrive and short stature. The proband also had distorted organ position and liver was centrally located and spleen was not identied at 1 week of age. Also had intestinal malformation and underwent Ladd procedure and gastrostomy tube placement at 3 weeks. The authors in this paper notes that NKX2-5 variants are associated with cardiac malformations that are commonly seen in patients with heterotaxy (i.e. transposition of great artieries and double outlet right ventricle) and also with asplenia in some patients.
After discussion with the Genomics England Clinical Team it was decided that this gene should remain Amber on this panel.
Created: 4 May 2021, 10:04 a.m. | Last Modified: 4 May 2021, 10:04 a.m.
Panel Version: 1.43
Comment on phenotypes: This gene is also associated with Ventricular septal defect 3, OMIM:614432;Tetralogy of Fallot, OMIM:187500
Created: 13 Apr 2021, 2:54 p.m. | Last Modified: 13 Apr 2021, 2:54 p.m.
Panel Version: 1.41
Gene is associated with congenital heart disease rather than laterality defects/heterotaxy.
Created: 1 Jun 2020, 9:57 a.m. | Last Modified: 1 Jun 2020, 9:57 a.m.
Panel Version: 1.5
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ventricular septal defect 3 (MIM#614432); Tetralogy of Fallot (MIM#187500)
Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: NKX2-5; Suggested initial gene rating: Amber; Evidence for inclusion: OMIM ASD7; unclear if associated w/laterality defects; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 5 Dec 2018, 12:52 p.m.
Publications for gene: NKX2-5 were set to 25742962; 26805889
Phenotypes for gene: NKX2-5 were changed from Ventricular septal defect 3, OMIM:614432; Tetralogy of Fallot, OMIM:187500 to visceral heterotaxy, MONDO:0018677
Phenotypes for gene: NKX2-5 were changed from to Ventricular septal defect 3, OMIM:614432; Tetralogy of Fallot, OMIM:187500
Mode of inheritance for gene: NKX2-5 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NKX2-5 were set to
Source Expert Review Amber was added to NKX2-5. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
gene: NKX2-5 was added gene: NKX2-5 was added to Laterality disorders and isomerism. Sources: NHS GMS Mode of inheritance for gene: NKX2-5 was set to