Reviewed August 2008
What is the official name of the KAL1 gene?
The official name of this gene is “Kallmann syndrome 1 sequence.”
KAL1 is the gene's official symbol. The KAL1 gene is also known by other names, listed below.
What is the normal function of the KAL1 gene?
The KAL1 gene provides instructions for making a protein called anosmin-1. This protein is involved in development before birth. Anosmin-1 is located on the surface of cells and may act as part of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells. Anosmin-1 is found in many parts of the developing embryo, including the respiratory tract, kidneys, digestive system, and certain regions of the brain.
Researchers are working to determine the functions of anosmin-1. They have discovered that, in the developing brain, this protein is involved in the movement (migration) of nerve cells and the outgrowth of axons, which are specialized extensions of nerve cells that transmit nerve impulses. The protein's structure suggests that it may also play a role in regulating contact between nerve cells (cell adhesion).
Anosmin-1 appears to help control the growth and migration of a group of nerve cells that are specialized to process smells (olfactory neurons). These nerve cells come together into a bundle called the olfactory bulb, which is critical for the perception of odors. Studies suggest that anosmin-1 is also involved in the migration of neurons that produce a hormone called gonadotropin-releasing hormone (GnRH). GnRH controls the production of several other hormones that direct sexual development before birth and during puberty. These hormones are important for the normal function of the gonads (ovaries in women and testes in men).
Does the KAL1 gene share characteristics with other genes?
The KAL1 gene belongs to a family of genes called fibronectin type III domain containing (fibronectin type III domain containing).
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 KAL1 gene related to health conditions?
- Kallmann syndrome - caused by mutations in the KAL1 gene
At least 60 mutations in the KAL1 gene have been identified in people with Kallmann syndrome type 1. In some cases, mutations delete part or all of the KAL1 gene. Other mutations change single protein building blocks (amino acids) in anosmin-1 or alter the size of the protein. Although KAL1 mutations disrupt the protein's normal function during embryonic development, it is unclear how these genetic changes lead to the characteristic features of Kallmann syndrome.
Researchers suspect that the altered anosmin-1 protein is unable to direct the migration of olfactory nerve cells and GnRH-producing nerve cells to their usual locations in the developing brain. If olfactory nerve cells do not extend to the olfactory bulb, a person's sense of smell will be impaired. Misplacement of GnRH-producing neurons prevents the production of certain sex hormones, which interferes with normal sexual development and causes puberty to be delayed or absent.
It is unknown how KAL1 mutations lead to other signs and symptoms of Kallmann syndrome, including a failure of one kidney to develop (unilateral renal agenesis), hearing loss, and mirror movements of the hands (bimanual synkinesia). Because the features of this condition vary among individuals, researchers believe that additional genetic and environmental factors are likely to be involved.
Where is the KAL1 gene located?
Cytogenetic Location: Xp22.32
Molecular Location on the X chromosome: base pairs 8,528,873 to 8,732,185
The KAL1 gene is located on the short (p) arm of the X chromosome at position 22.32.
More precisely, the KAL1 gene is located from base pair 8,528,873 to base pair 8,732,185 on the X chromosome.
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 KAL1?
You and your healthcare professional may find the following resources about KAL1 helpful.
Educational resources - Information pages
- Endocrinology: An Integrated Approach (first edition, 2001): GnRH and the control of gonadotrophin synthesis and secretion (http://www.ncbi.nlm.nih.gov/books/NBK29/)
- Neuroscience (second edition, 2001): The Olfactory Bulb (http://www.ncbi.nlm.nih.gov/books/NBK11158/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1334)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for KAL1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=3730%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=%28KAL1%5BTIAB%5D%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 (http://omim.org/entry/300836)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_KAL1.html)
- HGNC Gene Family: Fibronectin type III domain containing (http://www.genenames.org/cgi-bin/genefamilies/set/555)
- HGNC Gene Family: WAP four-disulfide core domain containing (http://www.genenames.org/cgi-bin/genefamilies/set/361)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=6211)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3730)
What other names do people use for the KAL1 gene or gene products?
- adhesion molecule-like X-linked
- Kallmann syndrome 1 protein
- Kallmann syndrome protein
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 KAL1?
adhesion molecule ;
cell adhesion ;
digestive system ;
extracellular matrix ;
olfactory bulb ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Albuisson J, Pêcheux C, Carel JC, Lacombe D, Leheup B, Lapuzina P, Bouchard P, Legius E, Matthijs G, Wasniewska M, Delpech M, Young J, Hardelin JP, Dodé C. Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2). Hum Mutat. 2005 Jan;25(1):98-9. (http://www.ncbi.nlm.nih.gov/pubmed/15605412?dopt=Abstract)
- Cadman SM, Kim SH, Hu Y, González-Martínez D, Bouloux PM. Molecular pathogenesis of Kallmann's syndrome. Horm Res. 2007;67(5):231-42. Epub 2006 Dec 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17191030?dopt=Abstract)
- Cariboni A, Pimpinelli F, Colamarino S, Zaninetti R, Piccolella M, Rumio C, Piva F, Rugarli EI, Maggi R. The product of X-linked Kallmann's syndrome gene (KAL1) affects the migratory activity of gonadotropin-releasing hormone (GnRH)-producing neurons. Hum Mol Genet. 2004 Nov 15;13(22):2781-91. Epub 2004 Oct 7. (http://www.ncbi.nlm.nih.gov/pubmed/15471890?dopt=Abstract)
- Gene Review: Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1334)
- Hardelin JP, Julliard AK, Moniot B, Soussi-Yanicostas N, Verney C, Schwanzel-Fukuda M, Ayer-Le Lievre C, Petit C. Anosmin-1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: implications for the developmental anomalies of X chromosome-linked Kallmann syndrome. Dev Dyn. 1999 May;215(1):26-44. (http://www.ncbi.nlm.nih.gov/pubmed/10340754?dopt=Abstract)
- Hardelin JP, Levilliers J, Blanchard S, Carel JC, Leutenegger M, Pinard-Bertelletto JP, Bouloux P, Petit C. Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome. Hum Mol Genet. 1993 Apr;2(4):373-7. (http://www.ncbi.nlm.nih.gov/pubmed/8504298?dopt=Abstract)
- Hardelin JP, Levilliers J, del Castillo I, Cohen-Salmon M, Legouis R, Blanchard S, Compain S, Bouloux P, Kirk J, Moraine C, et al. X chromosome-linked Kallmann syndrome: stop mutations validate the candidate gene. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8190-4. (http://www.ncbi.nlm.nih.gov/pubmed/1518845?dopt=Abstract)
- Kim SH, Hu Y, Cadman S, Bouloux P. Diversity in fibroblast growth factor receptor 1 regulation: learning from the investigation of Kallmann syndrome. J Neuroendocrinol. 2008 Feb;20(2):141-63. Epub 2007 Nov 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18034870?dopt=Abstract)
- Legouis R, Hardelin JP, Levilliers J, Claverie JM, Compain S, Wunderle V, Millasseau P, Le Paslier D, Cohen D, Caterina D, et al. The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell. 1991 Oct 18;67(2):423-35. (http://www.ncbi.nlm.nih.gov/pubmed/1913827?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3730)
- Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, Hasegawa Y, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T. Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. J Clin Endocrinol Metab. 2004 Mar;89(3):1079-88. (http://www.ncbi.nlm.nih.gov/pubmed/15001591?dopt=Abstract)
- Soussi-Yanicostas N, Faivre-Sarrailh C, Hardelin JP, Levilliers J, Rougon G, Petit C. Anosmin-1 underlying the X chromosome-linked Kallmann syndrome is an adhesion molecule that can modulate neurite growth in a cell-type specific manner. J Cell Sci. 1998 Oct;111 ( Pt 19):2953-65. (http://www.ncbi.nlm.nih.gov/pubmed/9730987?dopt=Abstract)
- Trarbach EB, Silveira LG, Latronico AC. Genetic insights into human isolated gonadotropin deficiency. Pituitary. 2007;10(4):381-91. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17624596?dopt=Abstract)
- Tsai PS, Gill JC. Mechanisms of disease: Insights into X-linked and autosomal-dominant Kallmann syndrome. Nat Clin Pract Endocrinol Metab. 2006 Mar;2(3):160-71. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16932275?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.