KDM3A

Cilia effects upon perturbation of KDM3A

Cilia number / % ciliated:

Incrased cilia number

Loss-of-function effect:

Longer cilia

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.19) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

small spleen, decreased prepulse inhibition, decreased thigmotaxis, decreased bone mineral content, lymphoid hyperplasia, hyperplasia, enlarged spleen, abnormal behavior, decreased anxiety-related response, hyperactivity, hypoplasia, abnormal bone structure, abnormal skin morphology

Mouse ciliopathy phenotype:

abnormal kidney morphology, small kidney, male infertility, eye hemorrhage

Subcellular localization

basal body, nucleus

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Reproduction & sperm
• Signaling (Hedgehog, GPCRs, ion channels)
• Transcription regulation

Function

Negative regulator of ciliogenesis required for the controlled recruitment of IFT proteins into cilia through the modulation of actin dy mics. It binds to the actin cytoskeleton, creating a responsive actin gate involving ARP2/3 activity and regulating IFT within cilia and periciliary compartments. In the absence of KDM3A, access to cilia is unrestricted, so the assembly and growth of primary cilia is enhanced (28246120). Absence of KDM3A facilitates ciliogenesis … these cilia have an abnormally wide range of axonemal lengths, delaying disassembly and accumulating IFT proteins. KDM3A is a negative regulator of ciliogenesis … required for controlled recruitment of IFT proteins into cilia via actin dynamics. (28246120)

Model organism evidence