Alternative titles; symbols
HGNC Approved Gene Symbol: NKX2-6
SNOMEDCT: 61959006, 787779000; ICD10CM: Q20.0; ICD9CM: 745.0;
Cytogenetic location: 8p21.2 Genomic coordinates (GRCh38): 8:23,701,740-23,706,756 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8p21.2 | Conotruncal heart malformations | 217095 | 3 | |
| Persistent truncus arteriosus | 217095 | 3 |
Homeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as determining the temporal and spatial patterns of development (Shiojima et al., 1995). It has been demonstrated that a Drosophila homeobox-containing gene called 'tinman' is essential for development of the heart-like dorsal vessel. NKX2-6 is a vertebrate homolog of 'tinman' (Newman and Krieg, 1998).
By database analysis, Heathcote et al. (2005) identified NKX2-6.
Heathcote et al. (2005) noted that the NKX2-6 gene maps to chromosome 8p21.
In affected members of a large consanguineous Kuwaiti family with persistent truncus arteriosus (PTA; see 217095), Heathcote et al. (2005) identified homozygosity for an F151L mutation (611770.0001) in the NKX2-6 gene.
In 3 sibs, born of consanguineous Palestinian parents, with conotruncal heart malformations (CTHM; 217095), Ta-Shma et al. (2014) identified a homozygous truncating mutation in the NKX2-6 gene (611770.0002). The mutation was found by exome sequencing.
Nikolova et al. (1997) reported that in mouse Nkx2-6 is expressed between embryonic day 8.5 and 10.5 with expression detected in all 3 layers of the caudal branchial arches.
Heathcote et al. (2005) reported that F151L-homozygous mice were normal, but that Nkx2-5 (600584) expression expanded into regions lacking Nkx2-6, suggesting functional complementation.
In a large consanguineous Kuwaiti family with persistent truncus arteriosus (PTA; see 217095), Heathcote et al. (2005) reported a 451T-C transition in exon 2 of the NKX2-6 gene, resulting in a phe151-to-leu (F151L) substitution in a conserved residue in the homeodomain. The mutation was not found in 900 control chromosomes.
In 3 sibs, born of consanguineous Palestinian parents, with conotruncal heart malformations (CTHM; 217095), Ta-Shma et al. (2014) identified a homozygous 1-bp insertion (c.453_454insT) in the NKX2-6 gene, resulting in premature termination (Lys152fsTer0). The mutation, which was found by exome sequencing, segregated with the disorder in the family and was not present in the dbSNP (build 132) or Exome Variant Server databases, or in 78 in-house control exomes. Two patients had persistent truncus arteriosus and 1 had a complex conotruncal defect and athymia. Functional studies of the variant were not performed.
Heathcote, K., Braybrook, C., Abushaban, L., Guy, M., Khetyar, M. E., Patton, M. A., Carter, N. D., Scambler, P. J., Syrris, P. Common arterial trunk associated with a homeodomain mutation of NKX2.6. Hum. Molec. Genet. 14: 585-593, 2005. [PubMed: 15649947] [Full Text: https://doi.org/10.1093/hmg/ddi055]
Newman, C. S., Krieg, P. A. Tinman-related genes expressed during heart development in Xenopus. Dev. Genet. 22: 230-238, 1998. [PubMed: 9621430] [Full Text: https://doi.org/10.1002/(SICI)1520-6408(1998)22:3<230::AID-DVG5>3.0.CO;2-7]
Nikolova, M., Chen, X., Lufkin, T. Nkx2.6 expression is transiently and specifically restricted to the branchial region of pharyngeal-stage mouse embryos. Mech. Dev. 69: 215-218, 1997. [PubMed: 9486544] [Full Text: https://doi.org/10.1016/s0925-4773(97)00174-3]
Shiojima, I., Komuro, I., Inazawa, J., Nakahori, Y., Matsushita, I., Abe, T., Nagai, R., Yazaki, Y. Assignment of cardiac homeobox gene CSX to human chromosome 5q34. Genomics 27: 204-206, 1995. [PubMed: 7665173] [Full Text: https://doi.org/10.1006/geno.1995.1027]
Ta-Shma, A., El-lahham, N., Edvardson, S., Stepensky, P., Nir, A., Perles, Z., Gavri, S., Golender, J., Yaakobi-Simhayoff, N., Shaag, A., Rein, A. J. J. T., Elpeleg, O. Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation. J. Med. Genet. 51: 268-270, 2014. [PubMed: 24421281] [Full Text: https://doi.org/10.1136/jmedgenet-2013-102100]