The missense of smell: functional variability in the human odorant receptor repertoire

Nat Neurosci. 2014 Jan;17(1):114-20. doi: 10.1038/nn.3598. Epub 2013 Dec 8.


Humans have ~400 intact odorant receptors, but each individual has a unique set of genetic variations that lead to variation in olfactory perception. We used a heterologous assay to determine how often genetic polymorphisms in odorant receptors alter receptor function. We identified agonists for 18 odorant receptors and found that 63% of the odorant receptors we examined had polymorphisms that altered in vitro function. On average, two individuals have functional differences at over 30% of their odorant receptor alleles. To show that these in vitro results are relevant to olfactory perception, we verified that variations in OR10G4 genotype explain over 15% of the observed variation in perceived intensity and over 10% of the observed variation in perceived valence for the high-affinity in vitro agonist guaiacol but do not explain phenotype variation for the lower-affinity agonists vanillin and ethyl vanillin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Female
  • Gene Frequency
  • Genetic Variation*
  • Genotype
  • Guaiacol / pharmacology
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Odorants
  • Olfactory Perception / genetics*
  • Polymorphism, Single Nucleotide
  • Psychophysics
  • Receptors, Odorant / genetics
  • Receptors, Odorant / metabolism*
  • Smell / physiology*
  • Young Adult


  • Receptors, Odorant
  • Guaiacol