There are some other things in ?genetic-modifications.csv.

Gene candidates for germline genetic modification

Direct gene candidates

CD47 suppression

gobs of radiation resistance. prevent binding of thrombospondin to CD47 with a drug, inhibits NO production and somehow this prevents radiation damage and kills cancer cells. antisense CD47 RNA should do the trick permanently.

Myostatin inhibition

There are a number of options here, but with germline modification, a muscle-specific knockout of ACVR2B or myostatin are good choices. Also follistatin overexpression in muscle.

PEPCK-C overexpression

In muscle, this allows greatly improved metabolism and endurance (see 'mighty mice'). Synergistic effect with myostatin inhibition is untested, but intriguing.

P53 overexpression

As the "guardian of the genome", p53 is missing in many cancers, and has been investigated as a gene therapy option for cancer. Introducing a separate copy, or copies of the gene from the wild-type could reduce the incidence of knockout mutations that normally lead to cancer.

milano allele

"Apolipoprotein A-1 Milano (also ETC-216, now MDCO-216) (ApoA-1 milano) is a naturally occurring mutated variant of the apolipoprotein A1 protein found in human HDL, the lipoprotein particle that carries cholesterol from tissues to the liver and is associated with protection against cardiovascular disease. ApoA1 Milano was first identified by Dr. Cesare Sirtori in Milan, who also demonstrated that its presence significantly reduced cardiovascular disease, even though it caused a reduction in HDL levels and an increase in triglyceride levels."

Alpha-galactosidase expression

Humans are unsuited to digesting some types of branching carbohydrates, which then pass through the intestines and feed annoying bacteria. Not a huge priority, but with the increased metabolic demands from the muscle-enhancing therapies, it can't hurt.

CCR5 knockout

Provides resistance to HIV and plague. Increases risk from West Nile virus, but who gives a fuck about that.

Also see HCP5 (rs2395029), and CCL3L1.

See also rs333 for other details.

LRP5 gene (strong bones)

Those with the LRP5 gene have extra strong bones.

PCSK5 (lower coronary disease)

Those with the PCSK5 gene have 88 percent lower coronary disease. Also, PCSK9 (according to George Church) is also capable of lowering susceptibility to coronary disease.

APP (Alzheimer's)

"More than 50 different mutations in the APP gene can cause early-onset Alzheimer disease, which begins before age 65."

Amyloid precursor protein

FUT2 (norovirus / stomach flu resistance)

Those with double FUT2 are resistant to stomach flu.


Lactase persistence (lactose tolerance);C)

Also known as "C/T(-13910)", and located in the MCM6 gene but with influence on the lactase LCT gene, rs4988235 is one of two SNPs that is associated with the primary haplotype associated with hypolactasia, more commonly known as lactose intolerance in European Caucasian populations. [PMID 11788828], [PMID 15114531]

In these populations, the rs4988235(T) allele is both the more common allele and the one associated with lactase persistence; individuals who are rs4988235(C;C) are likely to be lactose intolerant. In populations of sub-Saharan Africans, though, the rs4988235(T) allele is so rare that it's unlikely to be predictive of lactase persistence, and other SNPs are predictive instead. [PMID 15106124, PMID 17159977]

Resistance to weight gain from high-fat diets (APOA5)

rs662799 increases risk of heart attack, but contributes towards preventing weight gain from high fat diets.

Hyperosmia (increased odor sensitivity)

rs1953558 - sensitivity to sweaty odor (isovaleric acid)


rs6591536 - detection of β-ionone (floral) fragrance

Pain sensitivity


Malaria resistance

DARC - rs2814778

HBB - i3003137

G6PD - rs1050828


sweetness - TAS1R2

umami - TAS1R1

sourness - PKD2L1

spiciness - TRPV1

signal - GNAT3, TRPM5, PLCB2

bitterness - TAS2R4, TAS2R5, TAS2R16, TAS2R8, TAS2R38, TAS2R48

Sprinting vs. endurance

ACTN3 - rs1815739

Eye color

green eye color - rs7495174

blue eye color - rs12913832


Height SNPs

Hearing loss

SNPs related to hearing loss

Modulated alcohol cravings






Some loci associated with hippocampal volume found in genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8), enzymes targeted by new diabetes medications (DPP4), and neuronal migration (ASTN2).

  • DPP4 - rs6741949 - G allele, smaller hippocampus vlume
  • ASTN2 - rs7852872 - C allele, smaller hippocampus volume
  • rs7294919, located on 12q24 between HRK and FBXW8, T allele, smaller hippocampus volume
  • rs17178006 - smaller hippocampus volume
  • rs6581612, between WIF1 and LEMD3, smaller hippocampus volume

optimization of ubiquitin metabolism in hippocampus ? The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking. Also influences glutamate receptors.

  • rs733722, near the choline acetyltransferase CHAT gene, -- controls whether galantamine can help fight mental decline in Alzheimer's disease

Exceptional episodic memory:

  • rs9321334
  • MOXD1 (Monooxygenase, DBH-like 1) rs6902875 (when lacking an APOE ε4 allele); see also rs9321334 and rs4897574.

Working memory

The polymorphisms rs1800497 and rs2283265 (also known as the Taq1a polymorphism) near the dopamine receptor 2 (DRD2) gene are associated with improvements during working memory training. However this polymorphism comes with serious tradeoffs: antisocial, borderline, dissocial, and avoidant personality disorders, addictive and impulsive behaviors such as binge eating, pathological gambling, and drug abuse. (more)

Other genes and polymorphisms associated with working memory improvements are listed on page 5 table 1: SLC6A3 (DAT1) rs27072 rs40184 rs3863145; DRD4 rs11246226 rs936465 rs7124601; PPP1R1B (DARPP32) rs3764352; MAOA rs6609257; ANKK1 rs1800497 (TAQ1A); DRD2 rs2283265; LMX1A rs4657412; BDNF rs6265; COMT rs4680


SNPs in the SNAP25 gene were initially linked to intelligence but have failed to replicate. While now suspect, the original work can be found here.

Theoretical "heterozygote advantages" genes

The principle here is that diseases such as sickle cell or Tay-Sachs, among many others, persist in a population because having one 'good' and one 'bad' copy of the gene offers a significant advantage - in disease resistance, intelligence, etc.

While it would be nice to find a point mutation that would mimic the benefits of heterozygosity, the most straightforward option would be to give someone both variants of the gene, with ~50% expression of each.


mutations in:

  • FOXO3


  • APOB rs1801703, rs12713450, rs12720854


  • PPARGC1A rs148144750
  • NRG1 rs62497784
  • RAD52 rs35278212
  • NCOR1 rs61753150
  • RAD51 rs191297852
  • ADCY5 rs61734561
  • HLA-DRB5 rs71549220

  • PMS2

  • GABRR3

  • Various frameshift indels in TET2 and DNMT3A, and high levels of granulocytes in blood. "Both TET2 and DNMT3A are factors [28,29] and are thought to silence hematopoietic stem cell self-renewal to permit efficient hematopoietic differentiation [30,31]. Therefore, loss of functionality in these genes is likely to underlie an enhanced self-renewal leading to the observed age-related myeloid lineage bias. This skewing towards the myeloid lineage is assumed to have adverse effects on immune functionality in normal healthy individuals, but in the oldest old the increase of the myeloid compartment might be compensative for the age-related decrease in naive T-cells, known as immuno-senescence. Hence on condition that the enhanced self-renewal, instigated by somatic disruptive mutations in TET2 and DNMT3A, leads to increased levels of competent immune cells, be it of the myeloid lineage though, might partly compensate for the age-related loss of immuno-capacity of the lymphoid compartment." (from "Germ line and somatic characteristics of the long-lived genome")

Maybe also mutations in:

  • OBFC1 (telomere maintenance), rs77987791 rs77987791 rs7925084
  • GSK3B (healthy aging index)
  • NOTCH1 (diastolic blood pressure)
  • TP53 (serum HDL)
  • CTEP
  • ZNF562

... see "Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study".

  • DCAF4 -- avoid rs2535913; keep G because A is associated with lower leukocyte telomere lengths.

Other notes

Tetracycline response elements, i.e. tet-on and tet-off, can be used for transgenes where constant expression is undesirable. While a number of options for such inducible expression exist, the tet system is the most studied. It is left as an exercise to the reader to determine which genes would be suitable candidates [I will add some when I get around to it].

Candidate genes for sports doping

This is lifted from this table.

Gene/product System/organ targets Gene product properties Physiologic response
ACE skeletal muscles peptidyl dipeptidase ACE-D is involved in fast twitch muscles.
ACTN3 skeletal muscles actin-binding proteins related to dystrophin Involved in fast-twitch muscles.
endorphins central and peripheral nervous system widely active peptides pain modulation
EPO hematopoietic system glycoprotein hormone Increases RBC mass and oxygen delivery.
HGH endocrine system 191-amino acid protein Increases muscle size, power, and recovery.
HIF hematologic and immune systems multisubunit protein Regulates transcription at hypoxia response elements.
IGF-1 endocrine/metabolic/skeletal muscle 70-amino acid protein Increases muscle size, power, and recovery by increasing regulator cells.
myostatin (MSTN) skeletal muscle 2-subunit protein Regulates skeletal muscle. Inhibition increases muscle size, power, and recovery.
PPAR-delta skeletal muscle and adipose tissue nuclear hormone receptor protein Promotes fat metabolism and increases number of slow twitch fibers.
VEGF vascular endothelium glyosylated disulfide-bonded homodimers Induces development of new blood vessels.

Abbreviations: ACE, angiotensin-converting enzyme; ACTN3, actinin binding protein 3; EPO, erythropoetin; HGH, human growth factor; HIF, hypoxia inducible factor; IGF-1, insulin-like growth factor; PPAR-delta, peroxisome proliferators-activated receptor (delta); VEGF, vascular endothelial growth factor.


  • alpha-actin-3 for endurance and increased power in sprinters
  • myostatin and follistatin and muscle hypertrophy
  • erythropoietin for red blood cell production
  • insulin-like growth factor 1
  • "an increase in synthesis of monoamines could improve the mood of athletes"
  • preproenkephalin for pain reduction
  • glucagon-like peptide 1 to increase glucose in liver and reduce lactic acid buildups for athletes
  • endurance: ACE Alu I/D (rs4646994) (called ACE I); ACTN3 577X; PPARA rs4253778 G; PPARGC1A Gly482;
  • power/strength markers: ACE Alu I/D (rs4646994) (called ACE D); ACTN3 Arg577; AMPD1 Gln12; HIF1A 582Ser; MTHFR rs1801131 C; NOS3 rs2070744 T; PPARG 12Ala;
  • human tetrachromacy
  • rs17822931 - dry earwax, sweat production, body odor


4-5 hours of sleep/night, plus resistance to sleep deprivation -- see

"The transcriptional repressor DEC2 regulates sleep length in mammals" (hDEC2-P385R)

"A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans"

"Resisting sleep deprivation by breaking the link between sleep and circadian rhythms"

"TNFα G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults"



dental caries vaccine


a genetically modified strain of Streptococcus mutans called BCS3-L1, is incapable of producing lactic acid, which dissolves tooth enamel, and aggressively replaces native flora. In laboratory tests, rats who were given BCS3-L1 were conferred with a lifetime of protection against S. mutans. Dr. Jeffrey D. Hillman suggests that treatment with BCS3-L1 in humans could also provide a lifetime of protection, or, at worst, require occasional re-applications. He figures the treatment would be available in dentists' offices and "will probably cost less than $100.

paper: Genetically modified Streptococcus mutans for the prevention of dental caries

Cellular changes and molecular biology


Originally authored by yashgaroth on 2012-06-28. See for more context.