Genetic disease that makes thermoregulation voluntary

Question

I wonder if the disease I invented is realistic or a total fiction.

There is a real life genetic disease called congenital central hypoventilation syndrome (or Ondine's curse, if you want). People afflicted have a voluntary control of respiration (breathing).

In my story, there is a human that has a genetic disease called congenital central thermoregulation syndrome. That said human must voluntarily control its thermoregulation (this is less radical than The Human Torch from Disney/Marvel's The Fantastic Four, because its body does not turn into fire). Technically, that makes this human mesothermic (lukewarm-blooded) (like a tuna, a honey bee, a great white shark, and a platypus). The timescale is for each five minutes. The temperatures extremes are 18 to 42 Celsius degrees. There is a conscious signaling to brown adipose tissue.

If this genetic disease exists, what is its mode of inheritance? Autosomal dominant (like type 1 von Willebrand disease), autosomal recessive (like cystic fibrosis), X-linked dominant (like X-linked pituitary gigantism), X-linked recessive (like Hunter syndrome), incomplete dominance (like myostatin-associated muscular hypertrophy), or mitochondrial (like Leigh syndrome)?

If this is autosomal, what chromosome is linked? Chromosome 1 (like Hutchinson-Guilford progeria), chromosome 2 (like Ehlers-Danlos syndrome), chromosome 3 (like retinitis pigmentosa), chromosome 4 (like achondroplasia), chromosome 5 (like Sotos syndrome), chromosome 6 (like hemochromatosis), chromosome 7 (like tritanopia), chromosome 8 (like Werner syndrome), chromosome 9 (like cartilage-hair hypoplasia), chromosome 10 (like type 2 multiple endocrine hyperplasia), chromosome 11 (like sickle-cell anaemia), chromosome 12 (like phenylketonuria), chromosome 13 (like Wilson disease), chromosome 14 (like Krabbe disease), chromosome 15 (like Marfan syndrome), chromosome 16 (like Morquio syndrome), chromosome 17 (like type 1 neurofibromatosis), chromosome 18 (like type-C Niemann-Pick disease), chromosome 19 (like Donohue syndrome), chromosome 20 (like adenosine deaminase deficiency), chromosome 21 (like autoimmune polyendrocrinopathy-candidiasis-ectodermal-dystrophy), or chromosome 22 (like type 2 neurofibromatosis)?

I know I made an extremely long enumeration because the vast majority of the human genome is nuclear and autosomal, sorry.

Answer 1

Chromosome 4.

Chromosome 4 hosts the thermogenin gene. Thermogenin aka UCP1 regulates heat production by brown fat, which is one way mammals raise their body temperature. Thermogenesis is complicated but that is not an answer to this question!

If you feel like getting into the weeds some light reading: UCP1 Dependent and Independent Thermogenesis in Brown and Beige Adipocytes

It is an interesting proposal that thermogenesis could be consciously controlled. Thermogenesis is controlled by dopaminergic neurons which I thought were not under conscious control. Hypothalamic dopamine signalling regulates brown fat thermogenesis But maybe one can exert control.

Reinforcement learning links spontaneous cortical dopamine impulses to reward

Using a reinforcement learning paradigm based solely on rewards that were gated by feedback from real-time measurements of [DA]ex, we found that mice can volitionally modulate their spontaneous [DA]ex. In particular, by only the second session of daily, hour-long training, mice increased the rate of impulses of [DA]ex, increased the amplitude of the impulses, and increased their tonic level of [DA]ex for a reward. Critically, mice learned to reliably elicit [DA]ex impulses prior to receiving a reward...

Maybe the mutation in thermogenin makes it less autonomous and more reliant on dopaminergic control?

My proposal: the thermogenin mutation is recessive, and the double recessive is lethal because almost no-one has the volitional control of dopaminergic neurons necessary to rescue the phenotype. Double recessive babies die of cold. But your characters mother (and her family) has an autosomal dominant mutation in dopaminergic neurons putting them under greater volitional control. That turns out to be adaptive for this family in a number of ways unrelated to thermogenesis that you can explore in your story. Some ideas: An excess of dopaminergic activity produces the active symptoms of schizophrenia. A deficit produces symptoms like Parkinsons disease.

Your character is a double recessive thermogenin mutant with volitional dopaminergic powers. She figures out how to use those powers to keep warm when she is 3 weeks old.

As a child this person gradually becomes aware she is doing something different to keep warm. It helps that her mother has volitional dopamine control too (which of course she does not call that), but she (and her ancestors) can do things with her mind and body that other people can't. She teaches her child how to control these things. With that control comes control over body temperature too.

Pretty heady stuff but by the question I gather maybe you live there. Fun place to visit.