Alternative titles; symbols
HGNC Approved Gene Symbol: SOX14
Cytogenetic location: 3q22.3 Genomic coordinates (GRCh38): 3:137,764,315-137,766,334 (from NCBI)
SRY-related HMG-box (SOX) genes encode a family of DNA-binding proteins containing a 79-amino acid HMG (high mobility group) domain that shares at least 50% sequence identity with the DNA-binding HMG box of the SRY protein (480000). SOX proteins are divided into 6 subgroups based on sequence similarity within and outside of the HMG domain. For additional background information on SOX genes, see SOX1 (602148).
By PCR of human genomic DNA using highly degenerate oligonucleotides designed to amplify HMG box-related sequences, Cremazy et al. (1998) identified several novel SOX proteins, including SOX14, which they called SOX28. The partial SOX14 sequence encodes a deduced protein with an HMG box-like domain sharing 57% sequence identity with the SRY HMG box. Like the HMG box of SRY, the HMG box-like domain of SOX28 contains a putative nuclear localization signal.
By screening a genomic library using a SRY box-containing probe, Arsic et al. (1998) isolated the human SOX14 gene, which contains an HMG box identical to that of the partially characterized mouse Sox14 gene. The human SOX14 gene encodes a deduced 240-amino acid, proline-rich protein that contains several phosphorylation sites and a potential N-glycosylation site. The protein shows high similarity (87 to 92%) to the HMG-box region of other SOX proteins of the B subfamily, but lacks any similarity to those proteins outside of the HMG box. Northern blot analysis revealed expression of an approximately 1.8-kb SOX14 transcript in the liver-derived HepG2 cell line. With RT-PCR, expression was detectable in fetal brain, spinal cord, and thymus, with a lower level of expression in fetal adrenals and adult heart, liver, gut, kidney, and testes.
Hargrave et al. (2000) also reported the cloning and sequencing of the human ortholog of mouse and chick Sox14. They found that human SOX14 showed remarkable sequence conservation compared with orthologs from other vertebrate species and probably mirrored the expression of these genes in the developing brain and spinal cord.
Wilmore et al. (2000) stated that the SOX14 gene most closely resembles SOX21 (604974) with respect to nucleotide and amino acid sequence (Malas et al., 1999). Wilmore et al. (2000) found that the SOX14 amino acid sequence is highly conserved across human, mouse, and chicken orthologs, suggesting an important role for this protein in vertebrate development. SOX14 is expressed in the neural tube and apical ectodermal ridge of the developing chicken limb. Wilmore et al. (2000) stated that SOX14 is the only SOX gene known to be expressed in the apical ectodermal ridge, a structure that directs outgrowth of the embryonic limb bud.
Wilmore et al. (2000) stated that both the SOX14 and SOX21 genes appear to be encoded by a single exon. Arsic et al. (1998) determined that the SOX14 gene is intronless.
By fluorescence in situ hybridization (FISH), Arsic et al. (1998) mapped the SOX14 gene to chromosome 3q22-q23. By radiation hybrid analysis, they mapped the gene 3.46 cR distal to D3S1549 and proximal to D3S1576. Using radiation hybrid mapping and FISH, Hargrave et al. (2000) localized the SOX14 gene close to marker D3S1576 on 3q23. By FISH, Wilmore et al. (2000) mapped the SOX14 gene to 3q and further narrowed the assignment by screening a panel of YAC clones. They found that the SOX14 gene is localized to a 1.15-Mb YAC on 3q23, close to loci for blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES; 110100) and Moebius syndrome (MBS2; 601471).
Arsic, N., Rajic, T., Stanojcic, S., Goodfellow, P. N., Stevanovic, M. Characterisation and mapping of the human SOX14 gene. Cytogenet. Cell Genet. 83: 139-146, 1998. [PubMed: 9925951] [Full Text: https://doi.org/10.1159/000015149]
Cremazy, F., Soullier, S., Berta, P., Jay, P. Further complexity of the human SOX gene family revealed by the combined use of highly degenerate primers and nested PCR. FEBS Lett. 438: 311-314, 1998. [PubMed: 9827568] [Full Text: https://doi.org/10.1016/s0014-5793(98)01294-0]
Hargrave, M., James, K., Nield, K., Toomes, C., Georgas, K., Sullivan, T., Verzijl, H. T. F. M., Oley, C. A., Little, M., De Jonghe, P., Kwon, J. M., Kremer, H., Dixon, M. J., Timmerman, V., Yamada, T., Koopman, P. Fine mapping of the neurally expressed gene SOX14 to human 3q23, relative to three congenital diseases. Hum. Genet. 106: 432-439, 2000. [PubMed: 10830911] [Full Text: https://doi.org/10.1007/s004390000266]
Malas, S., Duthie, S., Deloukas, P., Episkopou, V. The isolation and high-resolution chromosomal mapping of human SOX14 and SOX21; two members of the SOX gene family related to SOX1, SOX2, and SOX3. Mammalian Genome 10: 934-937, 1999. [PubMed: 10441749] [Full Text: https://doi.org/10.1007/s003359901118]
Wilmore, H. P., Smith, M. J., Wilcox, S. A., Bell, K. M., Sinclair, A. H. SOX14 is a candidate gene for limb defects associated with BPES and Mobius syndrome. Hum. Genet. 106: 269-276, 2000. [PubMed: 10798354] [Full Text: https://doi.org/10.1007/s004390051037]