Affinage

CATSPERD

Cation channel sperm-associated auxiliary subunit delta · UniProt Q86XM0

Length
798 aa
Mass
90.5 kDa
Annotated
2026-04-28
8 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CATSPERδ (encoded by CATSPERD/TMEM146) is an essential auxiliary subunit of the sperm-specific CATSPER Ca²⁺-selective channel complex; loss of CATSPERδ in knockout mice abolishes the sperm Ca²⁺ current and prevents hyperactivated motility, resulting in male infertility (PMID:21224844). CATSPERδ is required for proper CATSPER channel assembly and/or trafficking to the sperm flagellum, and CATSPERδ-dependent hyperactivation is mechanistically necessary for sperm to interact with and penetrate the egg micropyle (PMID:21224844, PMID:41100162).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2011 High

    Identification of CATSPERδ as an essential auxiliary subunit of the CATSPER channel resolved the question of whether additional non-pore-forming components are required for channel function, showing that its absence eliminates sperm Ca²⁺ current, hyperactivated motility, and fertility.

    Evidence Tmem146 knockout mouse with electrophysiology, motility assays, co-immunoprecipitation, and fertility assessment

    PMID:21224844

    Open questions at the time
    • Structural basis of CATSPERδ interaction with the pore-forming CATSPER subunits is unknown
    • Whether CATSPERδ loss prevents channel assembly versus trafficking has not been resolved
    • Stoichiometry and topology of CATSPERδ within the channel complex remain undefined
  2. 2025 Medium

    Demonstrating that CATSPERδ-deficient sperm cannot interact with or cross the egg micropyle established a direct functional link between CATSPER-dependent hyperactivation and the mechanical process of egg penetration.

    Evidence Cross-species insemination of CatSperd knockout mouse sperm with zebrafish eggs, confocal and electron microscopy

    PMID:41100162

    Open questions at the time
    • Single cross-species assay; replication in a conspecific system would strengthen the conclusion
    • Whether CATSPERδ has additional roles beyond enabling hyperactivation during micropyle penetration is untested
    • Molecular mechanism by which hyperactivation facilitates micropyle crossing is not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural architecture of CATSPERδ within the CATSPER complex, whether CATSPERδ contributes to channel gating or solely to assembly/trafficking, and whether CATSPERD mutations cause human male infertility.
  • No high-resolution structural data for CATSPERδ or its interface with pore subunits
  • No human genetic studies directly linking CATSPERD variants to infertility in the timeline
  • Mechanism distinguishing assembly failure from trafficking failure in CATSPERδ-null sperm is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 1
Pathway
R-HSA-1474165 Reproduction 2
Partners
CATSPER1CATSPER2CATSPER3CATSPER4
Complex memberships
CATSPER channel complex

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 CATSPERD (encoded by Tmem146) is an essential auxiliary subunit of the CATSPER channel complex in sperm; mice lacking CATSPERδ are infertile, their spermatozoa lack Ca²⁺ current and hyperactivated motility, establishing CATSPERδ as required for proper CATSPER channel assembly and/or transport to the sperm tail. Gene knockout mouse model (loss-of-function), electrophysiology (Ca²⁺ current recording), motility assays, co-immunoprecipitation/complex analysis, sperm tail-specific expression characterization Nature Communications High 21224844
2025 CATSPERδ-deficient mouse sperm, which fail to undergo hyperactivation, cannot interact with or cross the zebrafish micropyle, demonstrating that hyperactive motility dependent on the CATSPER channel (including CATSPERδ) is mechanistically required for sperm entry into the egg micropyle. Cross-species insemination assay using CatSperd knockout mouse sperm, confocal and electron microscopy eLife Medium 41100162

Source papers

Stage 0 corpus · 8 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa. Nature communications 166 21224844
2020 Epigenome-wide association study identifies DNA methylation sites associated with target organ damage in older African Americans. Epigenetics 18 33100131
2023 Exome sequencing and functional analyses revealed CETN1 variants leads to impaired cell division and male fertility. Human molecular genetics 11 36048845
2022 Identification of Circular RNAs of Testis and Caput Epididymis and Prediction of Their Potential Functional Roles in Donkeys. Genes 8 36672807
2014 Identification of a novel isoform of the leukemia-associated MLLT1 (ENL/LTG19) protein. Gene expression patterns : GEP 3 25481096
2022 Neoexpression of JUNO in Oral Tumors Is Accompanied with the Complete Suppression of Four Other Genes and Suggests the Application of New Biomarker Tools. Journal of personalized medicine 2 35330493
2025 Cross-species insemination reveals mouse sperm ability to enter and cross the fish micropyle. eLife 0 41100162
2025 Genome-Wide Association Study of First-Parity Reproductive Traits in Suzi Pig. Genes 0 41300787