PRMT9

Cilia effects upon perturbation of PRMT9

Cilia number / % ciliated:

No effect

Loss-of-function effect:

Longer cilia

Ciliogenesis screen results (1 screen)

• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

increased grip strength; abnormal auditory brainstem response; improved glucose tolerance; increased mean corpuscular hemoglobin; increased mean corpuscular volume; cataract

Human ciliopathy phenotype:

Bi-allelic loss-of-function variants cause syndromic intellectual disability with global developmental delay, autism, epilepsy, hypotonia. Patient fibroblasts show abnormal primary cilia length under ciliogenesis conditions.

Ciliopathy associations

• Intellectual Developmental Disorder

Subcellular localization

cilia associated gene, cytosol, microtubules, nucleoplasm

Functional category

• Ciliary assembly/disassembly

Function

Pathogenic variants in PRMT9 affect the cilia length of skin fibroblasts from affected individuals. Multiple genes associated with intellectual disability, autism, or cilia biogenesis/function are dysregulated in individuals with bi-allelic PRMT9 pathogenic variants. MZprmt9ka709/ka709 mutants do not display a typical ciliopathy phenotype but show abnormal social preferences. transcriptomic analysis of fibroblasts from affected individuals indicated differential expression of genes related to intellectual disability, autism, and cilia, suggesting a role of PRMT9 during ciliogenesis. Under ciliogenesis conditions, the skin-derived fibroblasts exhibited anomalies in the length of primary cilia but normal amounts of cilia. In addition, a prmt9 knockout zebrafish model displayed abnormal social preference in adult animals(41260215).