NK2 HOMEOBOX 8; NKX2-8

Alternative titles; symbols

• NK2, DROSOPHILA, HOMOLOG OF, 8; NKX2.8
• NK2, DROSOPHILA, HOMOLOG OF, H; NKX2H
• NKX2-9, MOUSE, HOMOLOG OF

HGNC Approved Gene Symbol: NKX2-8

Cytogenetic location: 14q13.3 Genomic coordinates (GRCh38): 14:36,580,003-36,582,613 (from NCBI)

▼ Cloning and Expression
By screening a human hepatocarcinoma cell cDNA expression library for the ability to bind promoter-linked coupling element (PCE), which is a site from the alpha-fetoprotein (AFP; 104150) gene promoter, Apergis et al. (1998) isolated a cDNA encoding NKX2.8, a protein related to Drosophila nk2. The predicted 239-amino acid NKX2.8 protein is basic with a calculated pI of 9.6. NKX2.8 contains the characteristic homeobox and conserved peptide of nk2-related proteins. In vitro translated NKX2.8 protein migrated as an approximately 34-kD polypeptide by SDS-PAGE. Northern blot and RT-PCR analyses revealed that NKX2.8 is expressed as a 1.6-kb mRNA in fetal but not adult liver and in 3 cell lines with phenotypes that resemble those of fetal liver. Apergis et al. (1998) found that NKX2.8 shares several features with PCF, an AFP developmental regulator identified by Wen and Locker (1994): both bind PCE, activate transcription from PCE, and are expressed in the same cell types as AFP.

▼ Gene Family
Holland et al. (2007) stated that the NKX2-2 (604612) and NKX2-8 genes are collectively orthologous to Drosophila vnd and comprise the Nk2.2 gene family.

▼ Gene Structure
By analysis of genomic clones, Apergis et al. (1998) determined that the NKX2.8 gene contains a single intron. The open reading frame has an unusually high GC content of 71%.

Santagati et al. (2001) found that the sequence of NKX2.8 is most similar to that of Nkx2-9 in the mouse, and stated that the 2 genes are orthologous.

▼ Mapping
Santagati et al. (2001) observed conserved synteny between Pax9 (167416) and Nkx2-9 in 3 vertebrate species: humans, mice, and the Japanese pufferfish (Fugu rubripes). In the human, the NKX2.8 gene is located about 80 kb upstream of PAX9. PAX9 and NKX2.8 are oriented head to head on chromosome 14q12-q13.