WHSC1

Wolf-Hirschhorn syndrome candidate 1

The WHSC1 gene (also known as MMSET) provides instructions for making at least three very similar proteins known as MMSET I, MMSET II, and RE-IIBP. These proteins are active both before and after birth in many of the body's cells and tissues. They appear to play an important role in normal development.

At least two of the proteins produced from the WHSC1 gene, MMSET II and RE-IIBP, likely help regulate the activity of other genes. Studies suggest that these proteins function as histone methyltransferases, which are enzymes that modify DNA-associated proteins called histones. By adding a molecule called a methyl group to histones, histone methyltransferases can turn off (suppress) the activity of certain genes. Scientists are working to identify the genes targeted by the MMSET II and RE-IIBP proteins.

The WHSC1 gene is located in a region of chromosome 4 that is deleted in people with Wolf-Hirschhorn syndrome. As a result of this deletion, affected individuals are missing one copy of the WHSC1 gene in each cell. A loss of the WHSC1 gene probably disrupts the regulation of several other genes, although these genes have not been identified. Researchers speculate that abnormal gene regulation during development contributes to many of the characteristic features of the disorder, including intellectual disability, growth delay, and a distinctive facial appearance.

A chromosomal rearrangement (translocation) involving the WHSC1 gene has been associated with multiple myeloma, a cancer that starts in cells of the bone marrow. This rearrangement is found in 15 percent to 20 percent of all multiple myelomas. The translocation, which is written as t(4;14)(p16;q32), abnormally fuses the WHSC1 gene on chromosome 4 with part of another gene on chromosome 14. The fusion of these genes overactivates the WHSC1 gene, which appears to promote the uncontrolled growth and division of cancer cells.

Cytogenetic Location: 4p16.3, which is the short (p) arm of chromosome 4 at position 16.3

Molecular Location: base pairs 1,871,357 to 1,982,207 on chromosome 4 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 4p16.3, which is the short (p) arm of chromosome 4 at position 16.3
  • FLJ23286
  • IL5 promoter REII region-binding protein
  • KIAA1090
  • MGC176638
  • MMSET
  • multiple myeloma SET domain protein
  • NSD2
  • NSD2_HUMAN
  • Nuclear SET domain-containing protein 2
  • Probable histone-lysine N-methyltransferase NSD2
  • Protein trithorax-5
  • REIIBP
  • trithorax/ash1-related protein 5
  • TRX5