Affinage

CATSPERD

Cation channel sperm-associated auxiliary subunit delta · UniProt Q86XM0

Length
798 aa
Mass
90.5 kDa
Annotated
2026-06-09
8 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CATSPERD (TMEM146/CATSPERδ) is a sperm tail-specific auxiliary subunit of the sperm CATSPER Ca²⁺-selective channel complex, required for the channel's assembly and/or trafficking to the flagellum (PMID:21224844). Mice lacking CATSPERδ are infertile, and their spermatozoa lack the CatSper Ca²⁺ current and fail to undergo hyperactivated motility, establishing CATSPERδ as essential for functional channel formation (PMID:21224844). This CATSPER-dependent hyperactivation drives flagellar motility behaviors needed for sperm to locate and penetrate the egg, including crossing the fish micropyle in a cross-species insemination assay (PMID:41100162). Beyond its role in channel assembly and hyperactivated motility, no further molecular mechanism of CATSPERδ has been characterized in the available corpus.

Mechanistic history

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

    Established whether CATSPERδ is functionally required for the sperm Ca²⁺ channel, answering how loss of this subunit affects channel activity and fertility.

    Evidence Tmem146 knockout mouse with sperm electrophysiology, motility analysis, and localization studies

    PMID:21224844

    Open questions at the time
    • Does not resolve whether CATSPERδ acts in channel assembly versus membrane trafficking
    • No structural model of how CATSPERδ integrates into the CATSPER complex
    • Direct binding partners within the complex not biochemically mapped
  2. 2025 Medium

    Defined a specific motility consequence of CATSPERδ-dependent hyperactivation, showing it is required for sperm to locate and cross a physical egg barrier.

    Evidence Cross-species insemination assay with CatSperd-null mouse sperm plus confocal and electron microscopy

    PMID:41100162

    Open questions at the time
    • Single lab, single study with a heterologous (zebrafish micropyle) readout
    • Does not address physiological relevance in the native mammalian oviduct
    • Molecular link between Ca²⁺ current and the specific flagellar waveform not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical mechanism by which CATSPERδ promotes CATSPER channel assembly or trafficking, and its direct molecular partners, remain undefined.
  • No reconstitution or structural characterization of the CATSPERδ–channel interaction
  • No identified interacting subunits at residue resolution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
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 spermatozoa. Mice lacking CATSPERδ are infertile, and their spermatozoa lack both Ca²⁺ current (CatSper current) and hyperactivated motility, establishing CATSPERδ as required for CATSPER channel assembly and/or transport to the sperm tail. Gene knockout mouse model with electrophysiology (Ca²⁺ current measurement), sperm motility analysis, and localization studies demonstrating sperm tail-specific expression Nature communications High 21224844
2025 Hyperactivated motility dependent on CATSPERδ is required for sperm to locate and cross the fish micropyle during cross-species insemination. Sperm from CatSperd-null mice failed to interact with or cross the zebrafish micropyle, demonstrating that CATSPER-channel-dependent hyperactivation underlies this sperm motility function. Cross-species insemination assay using CatSperd knockout mouse sperm combined with 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 168 21224844
2020 Epigenome-wide association study identifies DNA methylation sites associated with target organ damage in older African Americans. Epigenetics 19 33100131
2023 Exome sequencing and functional analyses revealed CETN1 variants leads to impaired cell division and male fertility. Human molecular genetics 12 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

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