Reviewed January 2009
What is the official name of the WHSC1 gene?
The official name of this gene is “Wolf-Hirschhorn syndrome candidate 1.”
WHSC1 is the gene's official symbol. The WHSC1 gene is also known by other names, listed below.
What is the normal function of the WHSC1 gene?
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.
Does the WHSC1 gene share characteristics with other genes?
The WHSC1 gene belongs to a family of genes called PHF (PHD-type zinc fingers).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the WHSC1 gene related to health conditions?
- cancers - associated with the WHSC1 gene
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.
- Wolf-Hirschhorn syndrome - associated with the WHSC1 gene
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.
Where is the WHSC1 gene located?
Cytogenetic Location: 4p16.3
Molecular Location on chromosome 4: base pairs 1,871,396 to 1,982,207
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/7468))
The WHSC1 gene is located on the short (p) arm of chromosome 4 at position 16.3.
More precisely, the WHSC1 gene is located from base pair 1,871,396 to base pair 1,982,207 on chromosome 4.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about WHSC1?
You and your healthcare professional may find the following resources about WHSC1 helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1183)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for WHSC1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7468%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28WHSC1%5BTIAB%5D%29%20OR%20%28Wolf-Hirschhorn%20syndrome%20candidate%201%5BTIAB%5D%29%20OR%20%28MMSET%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- MYELOMA, MULTIPLE AMYLOIDOSIS, SYSTEMIC, INCLUDED (http://omim.org/entry/254500)
- WHS CANDIDATE 1 GENE (http://omim.org/entry/602952)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/WHSC1ID42809ch4p16.html)
- Atlas of Genetics and Cytogenetics in Oncology and Haematology: t(4;14)(p16;q32) (http://atlasgeneticsoncology.org/Anomalies/t04142059ID2059.html)
- HGNC Gene Family: PHD finger proteins (http://www.genenames.org/cgi-bin/genefamilies/set/88)
- HGNC Gene Family: PWWP domain containing (http://www.genenames.org/cgi-bin/genefamilies/set/1147)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=12766)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7468)
What other names do people use for the WHSC1 gene or gene products?
- IL5 promoter REII region-binding protein
- multiple myeloma SET domain protein
- Nuclear SET domain-containing protein 2
- Probable histone-lysine N-methyltransferase NSD2
- Protein trithorax-5
- trithorax/ash1-related protein 5
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding WHSC1?
bone marrow ;
gene regulation ;
multiple myeloma ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Bergemann AD, Cole F, Hirschhorn K. The etiology of Wolf-Hirschhorn syndrome. Trends Genet. 2005 Mar;21(3):188-95. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15734578?dopt=Abstract)
- Chesi M, Nardini E, Lim RS, Smith KD, Kuehl WM, Bergsagel PL. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood. 1998 Nov 1;92(9):3025-34. (http://www.ncbi.nlm.nih.gov/pubmed/9787135?dopt=Abstract)
- Keats JJ, Maxwell CA, Taylor BJ, Hendzel MJ, Chesi M, Bergsagel PL, Larratt LM, Mant MJ, Reiman T, Belch AR, Pilarski LM. Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients. Blood. 2005 May 15;105(10):4060-9. Epub 2005 Jan 27. (http://www.ncbi.nlm.nih.gov/pubmed/15677557?dopt=Abstract)
- Keats JJ, Reiman T, Belch AR, Pilarski LM. Ten years and counting: so what do we know about t(4;14)(p16;q32) multiple myeloma. Leuk Lymphoma. 2006 Nov;47(11):2289-300. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17107900?dopt=Abstract)
- Kim JY, Kee HJ, Choe NW, Kim SM, Eom GH, Baek HJ, Kook H, Kook H, Seo SB. Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone methyltransferase with transcriptional repression activity. Mol Cell Biol. 2008 Mar;28(6):2023-34. doi: 10.1128/MCB.02130-07. Epub 2008 Jan 2. (http://www.ncbi.nlm.nih.gov/pubmed/18172012?dopt=Abstract)
- Lauring J, Abukhdeir AM, Konishi H, Garay JP, Gustin JP, Wang Q, Arceci RJ, Matsui W, Park BH. The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity. Blood. 2008 Jan 15;111(2):856-64. Epub 2007 Oct 17. (http://www.ncbi.nlm.nih.gov/pubmed/17942756?dopt=Abstract)
- Marango J, Shimoyama M, Nishio H, Meyer JA, Min DJ, Sirulnik A, Martinez-Martinez Y, Chesi M, Bergsagel PL, Zhou MM, Waxman S, Leibovitch BA, Walsh MJ, Licht JD. The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor. Blood. 2008 Mar 15;111(6):3145-54. Epub 2007 Dec 21. (http://www.ncbi.nlm.nih.gov/pubmed/18156491?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7468)
- Stec I, Wright TJ, van Ommen GJ, de Boer PA, van Haeringen A, Moorman AF, Altherr MR, den Dunnen JT. WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma. Hum Mol Genet. 1998 Jul;7(7):1071-82. Erratum in: Hum Mol Genet 1998 Sep;7(9):1527. (http://www.ncbi.nlm.nih.gov/pubmed/9618163?dopt=Abstract)
- Todoerti K, Ronchetti D, Agnelli L, Castellani S, Marelli S, Deliliers GL, Zanella A, Lombardi L, Neri A. Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma. Br J Haematol. 2005 Oct;131(2):214-8. (http://www.ncbi.nlm.nih.gov/pubmed/16197452?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.