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

References: PMID:21715716, PMID:31545650, PMID:38568462

Subcellular localization

cilia

References: PMID:41410385, PMID:41005307, PMID:19889948, PMID:21715716, PMID:31545650, PMID:31942643

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• 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). Functional 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.