| PAFAH1B1 — Platelet Activating Factor Acetylhydrolase 1B Subunit 1 | |
|---|---|
| Symbol | PAFAH1B1 |
| Full Name | Platelet Activating Factor Acetylhydrolase 1B Subunit 1 (LIS1) |
| Chromosome | 17p13.3 |
| NCBI Gene | 5099 |
| Ensembl | ENSG00000007174 |
| OMIM | 601545 |
| UniProt | P43004 |
| Diseases | Lissencephaly, Miller-Dieker Syndrome, Alzheimer's Disease |
| Expression | Ubiquitously expressed; high expression in brain, particularly neurons |
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].
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.
The gene is located in the Miller-Dieker syndrome critical region on chromosome 17p13.3.
PAFAH1B1 contains:
PAFAH1B1 mutations are the most common cause of lissencephaly:
Classic Lissencephaly:
Miller-Dieker Syndrome:
Pathogenic variants:
Recent research implicates PAFAH1B1 in Alzheimer's disease:
PAFAH1B1 is ubiquitously expressed with highest levels in:
PAFAH1B1 expression is regulated during:
Reiner O, Carrozzo R, Shen Y, et al. "Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats." Nature. 1993;364(6439):717-721. DOI:10.1038/364717a0
Dobyns WB, Reiner O, Carrozzo R, et al. "Lissencephaly: a human brain malformation." JAMA. 1993;270(23):2838-2842. PMID: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;7(7):e39492. DOI:10.1371/journal.pone.0039492
Fahey B, Wigley K, Miao H, et al. "PAFAH1B1 regulates the development of cortical interneurons." Cerebral Cortex. 2021;31(10):4642-4657. DOI: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;79(9):912-931. DOI:10.1093/jnen/nlaa058