ABCA4

Cilia effects upon perturbation of ABCA4

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.40) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

vertebral fusion

Human ciliopathy phenotype:

cone-rod dystrophy 3; retinitis pigmentosa 19; retinitis pigmentosa; cone-rod dystrophy; Leber congenital amaurosis; autosomal recessive retinitis pigmentosa

Ciliopathy associations

• Cone-Rod Dystrophy
• Retinal Dystrophy/Degeneration

Subcellular localization

cilia associated gene, cytosol

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Metabolism
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Mutations in the ABCA4 gene cause Cone-Rod Dystrophy and Retinitis Pigmentosa(PMID: 12037008,PMID: 9425888). Comparative analysis between ABCA4-mutant and control ROs revealed distinct morphological alterations. Notably, ABCA4-mutant ROs demonstrated significantly reduced cone populations compared to control ROs, while maintaining comparable inner nuclear layer composition as indicated by HSP60 staining. This observation aligns with the previous findings showing opsin inhibition by Stargardt disease byproduct19. Intriguingly, synaptic structures in ABCA4-mutant ROs exhibited punctate appearance rather than the classic “horseshoe” morphology observed in controls, suggesting that ABCA4 mutations substantially impact cone morphology, particularly affecting outer segment and ciliary structural integrity. (40425564)