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AliasesNOTCH2NLA, N2N, notch 2 N-terminal like, notch 2 N-terminal like A, NOTCH2NL
External IDsHomoloGene: 89329 GeneCards: NOTCH2NLA
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for NOTCH2NLA
Genomic location for NOTCH2NLA
Band1q21.1Start146,146,203 bp[1]
End146,229,026 bp[1]
RefSeq (mRNA)



RefSeq (protein)


Location (UCSC)Chr 1: 146.15 – 146.23 Mbn/a
PubMed search[2]n/a
View/Edit Human

Notch homolog 2 N-terminal-like is a protein that in humans is encoded by the NOTCH2NL gene. It appears to play a key role in the development of the brain.[3][4][5][6]

NOTCH2NL increases the number of cortical stem cells, which while delaying the generation of neurons ultimately leads to a greater number of neurons and larger brains.[5] NOTCH2NL copy number loss and gain is associated with various neurological disorders, and they showed that loss of NOTCH2NL in human minibrains organoids leads to the organoids being smaller, while resulting in premature differentiation of cortical stem cells into neurons.[3][5] The role of NOTCH2NL in the development of the human brain together with the evolutionary history of NOTCH2NL genes, suggests that the emergence of NOTCH2NL genes may have contributed to the increase in size of the human neocortex which tripled over the last two million years.


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000264343 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:".
  3. ^ a b Fiddes IT, Lodewijk GA, Mooring M, Bosworth CM, Ewing AD, Mantalas GL, et al. (May 2018). "Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis". Cell. 173 (6): 1356–1369.e22. doi:10.1016/j.cell.2018.03.051. PMID 29856954.
  4. ^ Suzuki IK, Gacquer D, Van Heurck R, Kumar D, Wojno M, Bilheu A, Herpoel A, Lambert N, Cheron J, Polleux F, Detours V, Vanderhaeghen P (May 2018). "Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation". Cell. 173 (6): 1370–1384.e16. doi:10.1016/j.cell.2018.03.067. PMID 29856955.
  5. ^ a b c "Meet NOTCH2NL, the human-specific genes that may have given us our big brains". Eurekalert. 31 May 2018.
  6. ^ Yong E (31 May 2018). "A New Genetic Clue to How Humans Got Such Big Brains". The Atlantic.