PAFAH1B1 (Platelet Activating Factor Acetylhydrolase 1B Subunit 1), also known as LIS1, is a gene located on chromosome 17p13.3 that encodes a regulatory subunit of platelet-activating factor acetylhydrolase (PAFAH). PAFAH1B1 is a critical regulator of neuronal migration and cortical development. Mutations cause lissencephaly (smooth brain), a severe developmental brain malformation, and the gene has also been implicated in Alzheimer's disease and other neurological conditions [1][2].
Gene Structure
The PAFAH1B1 gene spans approximately 65 kb and consists of 11 exons. The gene encodes a 410-amino acid protein that functions in multiple cellular pathways.
Genomic Organization
Chromosome: 17p13.3
Location: chr17: 2590752-2743601
Strand: Plus strand
Exons: 11
The gene is located in the Miller-Dieker syndrome critical region on chromosome 17p13.3.
Protein Structure and Function
Domain Architecture
PAFAH1B1 contains:
WD40 repeat domain: Forms beta-propeller structure for protein-protein interactions
N-terminal region: Dimerization and regulatory functions
C-terminal region: Interaction with dynein/dynactin complex
Biological Functions
Neuronal Migration
Dynein regulation: PAFAH1B1 regulates the dynein-dynactin motor complex
Cortical development: Essential for neuronal migration during corticogenesis
Axonal guidance: Involved in axonal pathfinding
Cytoplasmic signaling: Modulates various signaling pathways
Other Functions
PAFAH enzymatic activity: Regulatory subunit of platelet-activating factor acetylhydrolase
[Dynein and Axonal Transport](/mechanisms/axonal-transport)
[Genes Index](/genes)
[Proteins Index](/proteins)
References
[Reiner O, Carrozzo R, Shen Y, et al, "Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats." Nature (1993)](https://doi.org/10.1038/364717a0)
[Dobyns WB, Reiner O, Carrozzo R, et al, "Lissencephaly: a human brain malformation." JAMA (1993)](https://pubmed.ncbi.nlm.nih.gov/7907010/)
[Sapir T, Frotscher M, Levy T, et al, "LIS1 RNA interference blocks neuronal stem cell progression and causes neuronal differentiation defects." PLoS ONE (2012)](https://doi.org/10.1371/journal.pone.0039492)
[Fahey B, Wigley K, Miao H, et al, "PAFAH1B1 regulates the development of cortical interneurons." Cerebral Cortex (2021)](https://doi.org/10.1093/cercor/bhab075)
[Kanaan NM, Kins S, Morfini G, et al, "LIS1 and dynein in neuronal function and disease." Journal of Neuropathology & Experimental Neurology (2020)](https://doi.org/10.1093/jnen/nlaa058)
Pathway Diagram
The following diagram shows the key molecular relationships involving PAFAH1B1 — Platelet Activating Factor Acetylhydrolase 1B Subunit 1 discovered through SciDEX knowledge graph analysis: