\nMedical Institute of Bioregulation \/ Institute for Advanced Study<\/span><\/strong><\/p>\n
Fukuoka, Japan\u2014From Tama, Japan\u2019s most famous stationmaster calico cat, to the lasagna-loving, ginger Garfield, cats with orange fur are both cultural icons and beloved pets. But their distinctive color comes with a genetic twist\u2014most orange tabbies are male, while calicos and tortoiseshells are nearly always female. This pattern points to an unknown \u201corange gene\u201d on the X chromosome, but identifying this gene has eluded scientists for decades.<\/p>\n
Now, researchers from Kyushu University, Japan, have found the X-linked mutation behind orange fur in house cats. This deletion mutation, a type of mutation where a section of DNA is missing, not only explains the peculiarity of ginger genetics, but also reveals an entirely new mechanism for promoting orange coloring in animals. The findings are confirmed by a second independent study by researchers at Stanford University, U.S., with both papers publishing simultaneously in Current Biology on May 15, 2025.<\/p>\n
\u201cIdentifying the gene has been a longtime dream, so it\u2019s a joy to have finally cracked it,\u201d says Professor Hiroyuki Sasaki, lead author of the study, self-proclaimed cat-lover, and geneticist at Kyushu University\u2019s Medical Institute of Bioregulation and the Institute for Advanced Study.<\/p>\n
![\"\"](\"https:\/\/sdgs.kyushu-u.ac.jp\/kanri\/wp-content\/uploads\/2025\/05\/cat.jpg\")
Fig. 1. Professor Hiroyuki Sasaki, a geneticist at Kyushu University with a soft spot for cats, makes fast friends with one of the calico cats at a local shelter while on his hunt for the gene behind orange fur. (Hiroyuki Sasaki\/Kyushu University)<\/p><\/div>\n
For over a century, scientists have suspected that the orange gene is located on the X chromosome. Male cats, with only one X chromosome, will have orange coats if they inherit the orange gene. Females, with two X chromosomes, need two copies of the gene to be fully orange, making them less common. If females inherit one orange and one black gene, they develop the patchy or mottled coats seen in calicos and tortoiseshells.<\/p>\n
\u201cThese ginger and black patches form because, early in development, one X chromosome in each cell is randomly switched off,\u201d explains Sasaki. \u201cAs cells divide, this creates areas with different active coat color genes, resulting in distinct patches. The effect is so visual that it has become the textbook example of X-chromosome inactivation, even though the responsible gene was unknown.\u201d<\/p>\n
![\"\"](\"https:\/\/sdgs.kyushu-u.ac.jp\/kanri\/wp-content\/uploads\/2025\/05\/pc_page-_cat-300x198.jpg\")
Fig. 2. Calico cats (left) and tortoiseshell cats (right) are the classic example of X chromosome inactivation, where either an orange color or a black color variant of a gene on the X chromosome is active in skin cells, resulting in orange and black patches. (Hiroyuki Sasaki\/Kyushu University)<\/p><\/div>\n
Armed with funding from a successful\u00a0crowdfunding campaign<\/a>, Sasaki therefore set out to find the elusive gene.<\/p>\n His team analyzed DNA from 18 cats\u201410 with orange fur and 8 without\u2014and found that all orange cats shared a specific deletion in the\u00a0ARHGAP36<\/em>\u00a0gene, while the non-orange cats did not. This pattern held true in 49 additional cats, including samples from an international cat genome database. They also found that in mice, cats, and humans, the\u00a0ARHGAP36<\/em>\u00a0gene is chemically marked for silencing during X chromosome inactivation, aligning perfectly with the long-standing hypothesis.<\/p>\n \u201cThis was such strong evidence that even at this stage, we were confident that\u00a0ARHGAP36<\/em>\u00a0was the orange gene,\u201d says Sasaki.<\/p>\n Looking closer at the mutation, Sasaki found that the deletion lies in a non-coding region of\u00a0ARHGAP36<\/em>, so the protein itself remains unchanged.<\/p>\n \u201cThis is key,\u201d he explains. \u201cARHGAP36<\/em>\u00a0is essential for development, with many other roles in the body, so I had never imagined it could be the orange gene. Mutations to the protein structure would likely be harmful to the cat.\u201d<\/p>\n Instead, Sasaki\u2019s team suspected the mutation altered the gene\u2019s activity. With help from local vets, they examined skin tissue from four calico cats and found that\u00a0ARHGAP36<\/em>\u00a0was much more active in melanocytes\u2014the pigment-producing cells found in skin\u2014in tissue taken from orange patches compared to tissue from black or white patches.<\/p>\n \u201cThis suggests that when present, this section of DNA normally suppresses\u00a0ARHGAP36<\/em>\u00a0activity,\u201d says Sasaki. \u201cWhen missing,\u00a0ARHGAP36<\/em>\u00a0stays active.\u201d<\/p>\n Further analysis showed that high\u00a0ARHGAP36<\/em>\u00a0activity is linked to reduced activity in many genes involved in melanogenesis, the process that produces pigment in skin and hair. Through a not yet known mechanism, the team believes this shift may steer pigment production from dark eumelanin to lighter pheomelanin, creating orange fur.<\/p>\n Fig. 3. Calico cats have X chromosomes that have two variants of the gene ARHGAP36. In orange patches of fur, the active chromosome (red) contains a deletion mutation in ARHGAP36, which increases its expression and reduces the activity of melanogenesis genes. This leads to higher levels of pheomelanin, resulting in ginger fur. In black patches of fur, the active chromosome (red) does not contain the deletion, and ARHGAP36 is suppressed. The activity of melanogenesis genes remains high, and eumelanin is produced, resulting in black fur. (Hiroyuki Sasaki\/Kyushu University)<\/p><\/div>\n Since\u00a0ARHGAP36<\/em>\u00a0is active in many areas of the body, including in areas of the brain and hormonal glands, it\u2019s possible that the orange variant may cause shifts in gene activity elsewhere, influencing more than just coat color.<\/p>\n \u201cFor example, many cat owners swear by the idea that different coat colors and patterns are linked with different personalities,\u201d laughs Sasaki. \u201cThere\u2019s no scientific evidence for this yet, but it\u2019s an intriguing idea and one I\u2019d love to explore further.\u201d<\/p>\n Sasaki has other big plans ahead, including using cat cell cultures to decipher the molecular function of\u00a0ARHGAP36<\/em>. Since the gene also exists in humans and is linked to conditions like skin cancer and hair loss, the findings could have surprising medical relevance.<\/p>\n He\u2019s also curious about the orange gene\u2019s origins, such as where and when the mutation happened. \u201cOne idea is to study ancient Egyptian cat paintings\u2014or even to test DNA from mummified cats\u2014to see if any cats back then were orange,\u201d he says. \u201cIt\u2019s ambitious, but I\u2019m excited to try.\u201d<\/p>\n Research-related inquiries<\/p>\n Hiroyuki Sasaki, Distinguished Professor<\/a>![\"\"](\"https:\/\/sdgs.kyushu-u.ac.jp\/kanri\/wp-content\/uploads\/2025\/05\/pc_page-_cat2.jpg\")
\nMedical Institute of Bioregulation<\/a>\u00a0\/\u00a0Institute for Advanced Study<\/a>
\nContact information can also be found in the\u00a0full release<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"A small deletion in a gene on the X-chromosome lies behind the fiery coats of ginger tabbies and the splotchy orange patches of calicos and tortoiseshell cats. Distinguished Professor Hiroyuki Sasaki Medical Institute of Bioregulation \/ Institute for Advanced Study Fukuoka, Japan\u2014From Tama, Japan\u2019s most famous stationmaster calico cat, to the lasagna-loving, ginger Garfield, cats […]","protected":false},"author":7,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[23,35],"tags":[43],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts\/25848"}],"collection":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/comments?post=25848"}],"version-history":[{"count":7,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts\/25848\/revisions"}],"predecessor-version":[{"id":25867,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/posts\/25848\/revisions\/25867"}],"wp:attachment":[{"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/media?parent=25848"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/categories?post=25848"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sdgs.kyushu-u.ac.jp\/en\/wp-json\/wp\/v2\/tags?post=25848"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}