Alternative titles; symbols
HGNC Approved Gene Symbol: DENND2B
Cytogenetic location: 11p15.4 Genomic coordinates (GRCh38): 11:8,693,352-8,910,951 (from NCBI)
The tumorigenicity of HeLa cells in nude mice can be suppressed by the addition of a normal human chromosome 11 in somatic cell hybrids (Stanbridge, 1976; Klinger, 1980); see 191181 for description of a tumor-suppressor gene located on 11q. Lichy et al. (1992) isolated a HeLa cell line that displayed morphologic features of the nontumorigenic hybrids, demonstrated reduced tumorigenicity in nude mice, and showed an 85% reduction in alkaline phosphatase, a consistent marker of the tumorigenic phenotype in these cells. This cell line, designated F2, contained a single exogenous cDNA, which was recovered by polymerase chain reaction (PCR) and designated HTS1 because of its probable association with 'HeLa tumor suppression.' In nontumorigenic hybrids, RNA species of 2.8, 3.1, and 4.6 kb were identified. In 2 tumorigenic hybrid lines, the 2.8-kb species was markedly reduced or absent. Whereas 3 nontumorigenic human keratinocyte lines expressed all 3 RNA species, several tumorigenic cervical carcinoma cell lines lacked the 2.8-kb species.
Gohring et al. (2010) noted that the ST5 gene encodes 3 isoforms with all 3 isoforms containing a C-terminal DENN domain but only isoforms 1 and 3 containing an ABL1-interacting domain. Quantitative PCR analysis detected a relatively uniform ST5 expression pattern in human fetal tissue. Expression in most human adult tissue was lower than in corresponding fetal tissues; however, adult expression was 2.5 to 3-fold higher in adult brain, kidney, and skeletal muscle compared to fetal tissue. In situ hybridization analysis of mouse embryos showed that St5 was expressed in neuroepithelium of the midbrain, telencephalon, and hindbrain, and later in the ventricular and marginal zone of the frontal cortex. Adult mice showed St5 expression in the cerebellum and hippocampus. Expression was also found in the heart and tubular structures of the kidney.
Gohring et al. (2010) noted that the ST5 gene contains at least 23 exons spanning 207.6 kb and that the first 4 exons are noncoding.
Lichy et al. (1992) localized the HTS1 gene to 11p15 by in situ hybridization, confirming the assignment to chromosome 11 by somatic cell hybrid analysis. They reviewed previous evidence indicating the presence of a tumor suppressor gene in the 11p15 region; see 194071 and 185440.
By genomic sequence analysis, Amid et al. (2001) mapped the ST5 gene to chromosome 11p15.3. They mapped the mouse St5 gene to distal chromosome 7 in a region that shows homology of synteny to human chromosome 11p15.3. In both genomes, ST5 lies telomeric to the CEGF1 gene and centromeric to the LMO1 gene (186921).
Gohring et al. (2010) reported a boy, first seen at age 3.5-years, with severe mental retardation, hypotonia, seizures, and sensorineural hearing loss associated with a de novo t(11;20)(p15.4;q13.2) translocation that interrupted the ST5 gene. Dysmorphic facial features included high forehead, high-arched and laterally placed eyebrows, narrow upslanting palpebral fissures, mild hypertelorism, broad glabella, small mouth with thin upper lip, cleft palate, broad nasal bridge, and hypoplastic nasal wings. Other features included persistent ductus arteriosus, unilateral cystic kidney dysplasia, and frequent infections. At age 7 years, he could walk with orthoses but had no speech development. He was born of healthy, unrelated parents who did not carry the translocation. Breakpoint analysis showed that the chromosome 11 breakpoint was in intron 4 in the 5-prime untranslated region of the ST5 gene, before the first coding exon 5. This was predicted to separate the complete coding sequence of the gene from its promoter region. The breakpoint on chromosome 20 did not occur in any known genes. Screening of the ST5 gene in 220 additional patients with mental retardation did not identify pathogenic mutations.
Amid, C., Bahr, A., Mujica, A., Sampson, N., Bikar, S.-E., Winterpacht, A., Zabel, B., Hankeln, T., Schmidt, E. R. Comparative genomic sequencing reveals a strikingly similar architecture of a conserved syntenic region on human chromosome 11p15.3 (including gene ST5) and mouse chromosome 7. Cytogenet. Cell Genet. 93: 284-290, 2001. [PubMed: 11528127] [Full Text: https://doi.org/10.1159/000056999]
Gohring, I., Tagariello, A., Endele, S., Stolt, C. C., Ghassibe, M., Fisher, M., Thiel, C. T., Trautmann, U., Vikkula, M., Winterpacht, A., FitzPatrick, D. R., Rauch, A. Disruption of ST5 is associated with mental retardation and multiple congenital abnormalities. J. Med. Genet. 47: 91-98, 2010. [PubMed: 19843505] [Full Text: https://doi.org/10.1136/jmg.2009.069799]
Klinger, H. P. Suppression of tumorigenicity in somatic cell hybrids. I. Suppression and reexpression of tumorigenicity in diploid human x D98/AH2 hybrids and independent segregation of tumorigenicity from other cell phenotypes. Cytogenet. Cell Genet. 27: 254-266, 1980. [PubMed: 6934067] [Full Text: https://doi.org/10.1159/000131494]
Lichy, J. H., Modi, W. S., Seuanez, H. N., Howley, P. M. Identification of a human chromosome 11 gene which is differentially regulated in tumorigenic and nontumorigenic somatic cell hybrids of HeLa cells. Cell Growth Differ. 3: 541-548, 1992. [PubMed: 1390339]
Stanbridge, E. J. Suppression of malignancy in human cells. Nature 260: 17-20, 1976. [PubMed: 1264187] [Full Text: https://doi.org/10.1038/260017a0]