ADD3 (adducin 3)

10q25.1

This gene is involved only in this translocation.

15 exons spanning 129.52 Kb on 10q25.1-10q25.2. Transcription is from centromere to telomere. 2-3 alternative transcripts.

Is membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network and binds to calmodulin. Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced adducin gamma transcripts encoding different isoforms have been described. The functions of the different isoforms are not known.

NUP98 (nucleoporin 98 kDa)

11p15.4

33 exons spanning 122.54 Kb on 11p15. Transcription is from centromere to telomere. 3-4 alternative transcripts.

Nup98 and Nup96 play a role in the bidirectional transport across the nucleoporin complex (NPC). The repeat domain in Nup98 has a direct role in the transport. Signal-mediated nuclear import and export proceed through the nuclear pore complex (NPC), which is comprised of approximately 50 unique proteins collectively known as nucleoporins. The 98 kD nucleoporin is generated through a biogenesis pathway that involves synthesis and proteolytic cleavage of a 186 kD precursor protein. This cleavage results in the 98 kD nucleoporin as well as a 96 kD nucleoporin, both of which are localized to the nucleoplasmic side of the NPC. The human gene has been shown to fuse to several genes following chromosome translocatons in acute myelogenous leukemia (AML) and T-cell acute lymphocytic leukemia (T-ALL). This gene is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described.