SIGLEC12 (sialic acid binding Ig-like lectin 12)

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Human Uniqueness Compared to "Great Apes": 
Absolute Difference
Human Universality: 
Individual Universal (All Individuals Everywhere)
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Siglec-XII Is a molecule found to be expressed on a few epithelial surfaces and on some macrophages in the chimpanzee. The gene underwent a human specific mutation of the critical arginine residue required for sialic acid binding. The roman numeral XII is used in place of -12 to designated this loss of sialic acid binding in the protein. This R122C mutation of the Siglec-XII protein is fixed in the human population, i.e. it occurred prior to the origin of modern humans. Additional mutations have since completely inactivated the SIGLEC12 gene in some but not all humans. The most common inactivating mutation is a single nucleotide frameshift that markedly shortens the open reading frame with a global allele frequency of 58%. Unlike other CD33-related Siglecs that are primarily found on immune cells, the Siglec-XII protein is expressed not only on some macrophages but also on various epithelial cell surfaces in humans and chimpanzees. Expression was also noted on certain human prostate epithelial carcinomas and carcinoma cell lines. The biological significance of this event is unknown at this time.


Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Possible Appearance (Lineage Separation Event): 
Probable Appearance (Lineage Separation Event): 
Definite Appearance (Lineage Separation Event): 
The Human Difference: 

Only Humans have the mutation in the critical arginine residue required for sialic acid recognition

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Topic Certainty
Sialic Acid Recognition by Siglecs Speculative
Genetics Topic Attributes
Gene symbols follow the HUGO Gene Nomenclature Committee standard.
Gene Symbol Type of Human-Specific Changes
SIGLEC12 Pseudogenization, Amino Acid Change, Polymorphism


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