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11h ago

Genetic Mutation Behind Orange Cat Fur Confirmed in Breakthrough Studies

Two independent research teams identify a 5.1-kb deletion in the X-linked ARHGAP36 gene as the cause of orange fur in domestic cats, revealing unique regulatory mechanisms and broader implications for biology.

A ginger domestic cat is resting lying on a gray sofa
Since ARHGAP36 is active in many areas of the body, including in areas of the brain and hormonal glands, it’s possible that the orange variant may cause shifts in gene activity elsewhere, influencing more than just coat color. Credit: Neuroscience News
Image
The sex-linked orange mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X inactivation in female tortoiseshell and calico cats; unlike the situation for most coat color genes, there is no apparent homolog for sex-linked orange in other mammals; Kaelin et al. show that sex-linked orange is caused by a 5-kb deletion that leads to ectopic and melanocyte-specific expression of the Arhgap36 gene. Image credit: Kaelin et al., doi: 10.1016/j.cub.2025.04.055.

Overview

  • The orange fur trait in domestic cats is caused by a 5.1-kilobase deletion in the ARHGAP36 gene, located on the X chromosome, as confirmed by two studies published in *Current Biology* on May 15, 2025.
  • This mutation increases ARHGAP36 activity in melanocytes, shifting pigment production from dark eumelanin to lighter pheomelanin, resulting in orange fur coloration.
  • The mutation’s location on the X chromosome explains why most orange cats are male, while females with one copy of the gene develop calico or tortoiseshell patterns due to random X-chromosome inactivation.
  • The ARHGAP36 deletion represents a rare case of a non-coding regulatory mutation driving a visible phenotype and has no known homolog in other mammals, indicating a unique evolutionary origin in domestic cats.
  • Researchers are now investigating the broader biological roles of ARHGAP36, including potential effects on brain and hormonal activity, as well as medical insights into human conditions like skin cancer and hair disorders.