SPEF2

Cilia effects upon perturbation of SPEF2

Cilia number / % ciliated:

No effect

Loss-of-function effect:

Decrease

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Human ciliopathy phenotype:

primary ciliary dyskinesia

Ciliopathy associations

• Male Infertility
• Primary Ciliary Dyskinesia

Subcellular localization

cilia

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• T cell biology
• Reproduction & sperm
• Cell migration & adhesion

Function

Essential for correct sperm tail development and male fertility. Interacts with intraflagellar transport protein IFT20. Mutation in SPEF2 was identified as a cause for immotile short tail sperm in pigs (19889948). Required for ciliary motility and spermatogenesis. In mouse, loss of SPEF2 function results in PCD with severe spermatogenic defects (21715716). Functio l defects also lead to PCD due to a defect of the central pair complex. Interacts with HYDIN, which regulates assembly of SPEF2 to the ciliary axoneme, as it cannot be detected in the axonemes of HYDIN-mutant cells (31545650). Required for the flagellar assembly of central pair complex and peri- axonemal structure in humans (31942643). SPEF2 variants cause PCD/PCD-like phenotype and male infertility via absence of central pair complex in sperm flagella. Confirmed pathogenic in 3 families; ICSI successful. Immunostaining of respiratory cilia confirms pathogenicity.

Model organism evidence