Alternative titles; symbols
HGNC Approved Gene Symbol: TSSC4
Cytogenetic location: 11p15.5 Genomic coordinates (GRCh38): 11:2,400,750-2,403,876 (from NCBI)
The TSSC4 gene is a nonimprinted tumor suppressor gene that resides in the imprinted gene domain on chromosome 11p15.5 (Lee et al., 1999).
Because of the large number of imprinted genes on 11p15, spanning approximately 1 Mb, this region appears to represent 1 of 2 known large imprinted domains in the human genome, the other being the Prader-Willi/Angelman syndrome domain of 15q11-q13 (see 105830). Koi et al. (1993) isolated a subchromosomal transferable fragment (STF) that suppresses in vitro growth of the rhabdomyosarcoma cell line RD, confirming the existence of 1 or more tumor suppressor genes within this region. Hu et al. (1997) found that the STF spans approximately 2.5 Mb, with D11S12 at its proximal end and D11S1318 at its distal end. Within a cluster of imprinted genes in this STF, Lee et al. (1999) identified 2 novel genes, designated TSSC4 and TSSC6 (603853), that were not imprinted in any of the fetal or extraembryonic tissues examined. The TSSC4 cDNA encodes a predicted protein of 349 amino acids that shows no close similarity to previously reported proteins. Northern blot analysis revealed that the TSSC4 gene was expressed as an approximately 1.6-kb transcript in fetal brain, lung, liver, and kidney. The TSSC4 and TSSC6 genes are both located in the center of the 1-Mb imprinted domain on 11p15 that contains the 7 imprinted genes. Thus, the imprinted gene domain of 11p15 appears to contain at least 2 imprinted subdomains, between which the TSSC4 and TSSC6 genes substantially escape imprinting, due either to a lack of initial silencing or to an early developmental relaxation of imprinting.
Lee et al. (1999) noted that 7 imprinted genes had been identified on 11p15: IGF2 (147470), which encodes an important autocrine growth factor in cancer; H19 (103280), an untranslated RNA whose imprinting regulates IGF2; ASCL2 (601886), a homolog of Drosophila achaete-scute that is expressed in the trophoblast; KCNQ1 (607542), which encodes a voltage-gated potassium channel; p57(KIP2) (CDKN1C; 600856), which encodes a cyclin-dependent kinase inhibitor; TSSC5 (IMPT1; 602631), which encodes a predicted transmembrane transporter; and TSSC3 (602131), also known as IPL, a homolog of a mouse apoptosis-inducing gene. With the exception of IGF2, all of these genes are expressed from the maternal allele.
Hu, R.-J., Lee, M. P., Connors, T. D., Johnson, L. A., Burn, T. C., Su, K., Landes, G. M., Feinberg, A. P. A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes. Genomics 46: 9-17, 1997. [PubMed: 9403053] [Full Text: https://doi.org/10.1006/geno.1997.4981]
Koi, M., Johnson, L. A., Kalikin, L. M., Little, P. F. R., Nakamura, Y., Feinberg, A. P. Tumor cell growth arrest caused by subchromosomal transferable DNA fragments from chromosome 11. Science 260: 361-364, 1993. [PubMed: 8469989] [Full Text: https://doi.org/10.1126/science.8469989]
Lee, M. P., Brandenburg, S., Landes, G. M., Adams, M., Miller, G., Feinberg, A. P. Two novel genes in the center of the 11p15 imprinted domain escape genomic imprinting. Hum. Molec. Genet. 8: 683-690, 1999. [PubMed: 10072438] [Full Text: https://doi.org/10.1093/hmg/8.4.683]