Upgrade, a book by Blake Crouch, is one of my favorite sci-fi stories. In it, the main characters are shotgun edited by their mother with superhuman abilities. There is a lot of technology to be developed from that book that I would like to work on.
In the book, there are tons of genes that are discussed. I list the ones mentioned below, more for my own reference, but I figured I would share. Most of these are real, but some are made up by Blake to enhance the story.
In my opinion, what counts is not the statistical percentage of one gene affecting some English-described phenotype like eye color or hair color, like what we get with tests like Nucleus and Nebula, but the real molecular biology this gene causes. Understanding this leads to insane engineering ability.
LOF = loss of function, meaning if it doesn’t work, the right side of the arrow (→) is the byproduct
So it goes: gene function → LOF byproduct
SOST: inhibits Wnt signaling in bone → high bone mass
MSTN: negative regulator of muscle growth → large, lean muscles (seen in cattle & rare humans)
SCN9A: Nav1.7 sodium channel → insensitivity to pain
FAAH-OUT: reduced FAAH activity increases endocannabinoids, lowering pain and anxiety
NTRK1: NGF receptor (TrkA) → insensitivity to pain + anhidrosis
HSD17B13: Hepatic lipid metabolism → protection from fatty liver disease
CCR5: HIV coreceptor → HIV resistance
FUT2: Gut epithelial glycosylation → Norovirus resistance
IL23R: Th17 immune signaling → protection from Crohn’s disease
HBB: Hemoglobin β-chain → Malaria resistance
PAH (PKU in book): Phenylalanine metabolism lowers → loss causes toxic phenylalanine accumulation and neurodevelopmental disease
CFTR: Chloride channel → possibly TB/cholera resistance
HEXA: GM2 ganglioside degradation → possible TB resistance (speculative)
PCSK9: LDL receptor degradation → very low LDL, low heart disease risk
GHR/GH/SLC30A8: Growth hormone axis / insulin secretion → diabetes, stature, longevity tradeoffs
IFIH1=MDA5: viral RNA sensing → reduced autoimmunity, altered viral defense
NPC1: cholesterol trafficking → Ebola resistance
ANGPTL3: lipid metabolism regulator → low triglycerides and LDL
EGLN1/EPAS1: oxygen sensing → high-altitude tolerance
MTHFR: folate metabolism → not sure
EPOR: red blood cell production → oxygen delivery changes
BHLHE41=DEC2: sleep duration regulation → natural short sleepers
NPSR1: arousal, anxiety → wakefulness, stress response
ADRB1: Noradrenergic signaling → wakefulness
APOE: ε2 → protective, ε4 → increases Alzheimer’s risk
APP/NGF/NEU1/NGFR: neuronal survival, amyloid processing → heavily drug-targeted, tightly regulated
CTNNB1 (β-catenin): Wnt signaling → cancer is not a simple LOF story; loss breaks development, persistent activation drives oncogenesis
CDKN2A/TP53: tumor suppression → enhancement ≠ trivial; dosage matters (needs better engineering tools)
TERT: Telomerase → longevity or cancer
AAVS1 (PPP1R12C intron 1): safe-harbor integration site on human chromosome 19 for CRISPR knock-in
SHS231: not real
hROSA26: human ROSA26-like safe-harbor locus (less standardized than in mouse, since we have done so much with mice but not a lot with humans)