Why Orange Cats Are (Mostly) Boys: Science cracks the code (#329)

For years, the genetic mystery of orange cats has gone unsolved. While their personalities have long inspired memes, comic strips, and children’s books, the biological roots of their fiery coats remained elusive.

A recent breakthrough by Japanese geneticist Hiroyuki Sasaki and his team at Kyushu University has finally traced the orange gene to its source.

Their research not only explains why so many orange cats are male, but also opens fascinating new questions about how coat color, pigment biology, and even personality might be interwoven in these charismatic cats.

The Mystery of the Orange Coat

From Garfield to Heathcliff to Morris, orange cats have enjoyed a kind of fame their tuxedo and tabby cousins rarely match.

But how did they get that eye-catching, marmalade hue?

The answer lies in a specific gene called ARHGAP36. While not previously linked to fur pigmentation, this gene became the focus of Sasaki’s attention as he compared skin tissue from cats with and without orange coats. What he found was striking: a deletion mutation. A missing segment of genetic code in the noncoding (intron) region of ARHGAP36. This region doesn’t make proteins directly, but it plays a regulatory role in how genes are expressed.

Here’s the twist: ARHGAP36 isn’t just involved in pigment production. It’s also active in neuroendocrine tissues, including the hypothalamus, adrenal glands, and pituitary glands. These are key centers in hormone regulation and brain function. That intriguing overlap has prompted speculation:

This mutation might influence not just how orange cats look, but also how they behave.

Orange Is an X-Linked Affair

The orange gene is X-linked, meaning it resides on the X chromosome. And this explains one of the most striking statistics in feline genetics: the majority of orange cats are male.

Male cats have just one X chromosome (paired with one Y), so if that lone X carries the ARHGAP36 mutation, it’s expressed uniformly across their body.

Voilà: an all-orange cat.

Female cats, however, have two X chromosomes. To be entirely orange, a female must have the mutation on both of her Xs. A less likely genetic combination.

More often, female cats inherit one orange-coded X and one non-orange X, resulting in those exquisite calico or tortoiseshell patterns, where patches of orange intermingle with black, gray, or brown. This occurs due to X-inactivation, where one X chromosome is randomly turned off in each cell during early development.

Male calicos are almost unheard of. This is only possible when a cat has two X chromosomes and a Y (XXY). A rare chromosomal configuration.

The Science of Color: Melanins in Action

All fur color in mammals comes down to two key pigments: eumelanin (black or brown) and pheomelanin (red or yellow).

In Sasaki’s study, ARHGAP36 was found to be highly active in melanocytes in orange fur patches. His findings suggest that mutated ARHGAP36 suppresses eumelanin production, clearing the stage for pheomelanin to dominate.

Think of it like this: the missing segment in the mutated gene removes the brakes that would normally inhibit orange coloration. Without those brakes, the cat’s biology swerves toward the production of pheomelanin, resulting in that distinct reddish-orange glow.

Interestingly, pheomelanin is also the pigment behind red hair in humans and the bright feathers of certain birds, highlighting a cross-species role for this pigment in flamboyant displays.

Rick’s Commentary

Sasaki’s team is cautious but curious about what this might mean for the orange cat personality, so often described as bold, quirky, or just a bit unhinged. Because ARHGAP36 is active in the brain as well as in pigmentation pathways, the question arises:

Could this gene influence behavior as well as color?

No definitive link has been established (yet!), but the overlap is too tantalizing to ignore. And it may offer a glimmer of scientific credibility to the millions of internet users who suspect that orange cats are, well, a little extra.

Although we now have a clearer picture of how orange cats get their color, thanks to a deletion mutation in ARHGAP36, there’s still much we don’t know.

The exact mechanism by which this gene tilts the balance toward pheomelanin, and how it might shape behavior, remains to be unraveled.

For now, though, Sasaki and his team have given us a valuable piece of the puzzle. And orange cats everywhere can strut a little prouder, their flamboyant coats no longer a mystery, but a marvel of evolutionary biology and chromosomal serendipity.

Sources

• A deletion at the X-linked ARHGAP36 gene locus is associated with the orange coloration of tortoiseshell and calico cats. This study, led by Hiroyuki Sasaki and colleagues at Kyushu University, identified a 5.1-kilobase deletion within an intron of the X-linked ARHGAP36 gene. This deletion is closely associated with orange coloration in domestic cats. Published in Current Biology, May 2025. https://www.cell.com/current-biology/fulltext/S0960-9822%2825%2900391-4

• Molecular and genetic characterization of sex-linked orange coat color in the domestic cat. Conducted by researchers at Stanford University, this study corroborated the findings regarding the ARHGAP36 gene's role in orange fur coloration. It also explored the gene's expression in melanocytes. Published in Current Biology, May 2025. https://www.cell.com/current-biology/abstract/S0960-9822%2825%2900552-4

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