FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: azoospermia (postulated), TDRKH-related
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General Information
Name
azoospermia (postulated), TDRKH-related
FlyBase ID
FBhh0000236
Disease Ontology Term
Parent Disease
OMIM
Overview

Identified in a GWAS analysis of Chinese men with non-obstructive azoospermia (FBrf0227519), the human gene TDRKH is proposed as a candidate gene for involvement in human male fertility. TDRKH (Tudor and KH domain-containing) protein participates in the primary piRNA biogenesis pathway and is required during spermatogenesis to repress transposable elements. There is a single Drosophila ortholog, papi, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.

The human TDRKH gene has not been introduced into flies.

In Drosophila, systemic knockdown of the Dmel\papi using GAL4/UAS-RNAi results in male sterility.

[updated Apr. 2016 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: azoospermia, non-obstructive
Symptoms and phenotype

Non-obstructive azoospermia (NOA) is defined as absence of any measurable level of sperm in semen, resulting from a defect in the production of spermatozoa in the testes. [from MedGen, Non-obstructive azoospermia; MedGen UID: 866757]

(FlyBase Curators, 2013-)

Non-obstructive azoospermia (NOA), or failure of spermatogenesis within the testis, is diagnosed in approximately 10% of infertile men. NOA may be due to a lack of appropriate stimulation by gonadotropins, in which case hormonal therapy is usually effective. A larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment. In these cases, the primary approach is to improve the quantity and quality of sperm retrieved from the testis for use for in vitro fertilization (Kumar, 2013; PMCID:PMC3583162).

(FlyBase Curators, 2013-)
Specific Disease Summary: azoospermia (postulated), TDRKH-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Observation of non-obstructive azoospermia (NOA).

(Yu et al., 2015)
Genetics

Locus identified in a genome-wide association study (GWAS) of non-obstructive azoospermia in Chinese men.

(Yu et al., 2015)
Cellular phenotype and pathology
Molecular information

TDRKH (Tudor and KH domain-containing) protein participates in the primary piRNA biogenesis pathway and is required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. [from UniProt:Q9Y2W6; 2016.04.07]

(FlyBase Curators, 2013-)
External links
Disease synonyms
male infertility
non-obstructive azoospermia
spermatogenic failure
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    TDRKH; tudor and KH domain containing
    D. melanogaster ortholog (based on DIOPT)
    Dmel\papi
    (DIOPT, 2013-)
    Comments on ortholog(s)

    One to one: 1 human to 1 Drosophila.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\papi
      Gene Snapshot
      Contributions welcome
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
        Comments on ortholog(s)

        Ortholog of human TDRKH (1 Drosophila to 1 human). Dmel\papi shares 27% identity and 46% similarity with human TDRKH.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        H. sapiens (Human)
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (6 groups)
          papi
          protein-protein
          Interacting group
          Assay
          References
          papi - AGO3
          anti bait coimmunoprecipitation, western blot, two hybrid
          (Liu et al., 2011)
          papi - aub
          anti bait coimmunoprecipitation, western blot, isothermal titration calorimetry, predetermined participant, two hybrid
          (Zhang et al., 2018, Liu et al., 2011)
          papi - me31B
          anti bait coimmunoprecipitation, western blot
          (Liu et al., 2011)
          papi - piwi
          two hybrid, anti tag coimmunoprecipitation, anti tag western blot, x-ray crystallography, isothermal titration calorimetry, predetermined participant, pull down, western blot, Identification by mass spectrometry, anti bait coimmunoprecipitation, molecular weight estimation by staining
          (Zhang et al., 2018, Liu et al., 2011)
          papi - TER94
          anti bait coimmunoprecipitation, western blot
          (Liu et al., 2011)
          papi - tral
          anti bait coimmunoprecipitation, western blot
          (Liu et al., 2011)
          Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
          papi
          Models Based on Experimental Evidence ( 1 )
          Allele
          Disease
          Evidence
          References
          papiRNAi.UAS.THFC
          model of  azoospermia
          CEA
          (Yu et al., 2015)
          Modifiers Based on Experimental Evidence ( 0 )
          Allele
          Disease
          Interaction
          References
          Alleles Representing Disease-Implicated Variants
          Genetic Tools, Stocks and Reagents
          Sources of Stocks
          Contact lab of origin for a reagent not available from a public stock center.
          Bloomington Stock Center Disease Page
          Related mammalian, viral, bacterial, or synthetic transgenes
          Allele
          Transgene
          Publicly Available Stocks
          Selected Drosophila transgenes
          Allele
          Transgene
          Publicly Available Stocks
          RNAi constructs available
          Allele
          Transgene
          Publicly Available Stocks
          papiGD828
          P{GD828}
          w1118 P{GD828}v2554
          papiKK100642
          P{KK100642}
          P{KK100642}VIE-260B
          papiGL00375
          P{TRiP.GL00375}
          y1 sc* v1 sev21; P{TRiP.GL00375}attP2/TM3, Sb1
          papiHMS01282
          P{TRiP.HMS01282}
          y1 sc* v1 sev21; P{TRiP.HMS01282}attP2/TM3, Sb1
          papiRNAi.UAS.V22
          P{UAS-papi.RNAi.V22}
          papiHMS01655
          P{TRiP.HMS01655}
          y1 sc* v1 sev21; P{TRiP.HMS01655}attP40
          papiNIG.7082R
          P{NIG.7082R}
          P{NIG.7082R}1
          papiGL00657
          P{TRiP.GL00657}
          y1 v1; P{TRiP.GL00657}attP40
          papiRNAi.UAS.THFC
          P{UAS-papi.RNAi.THFC}
          papiRNAi.zp.UAS
          P{UAS-zuc.papi.RNAi}
          Selected Drosophila classical alleles
          Allele
          Allele class
          Mutagen
          Publicly Available Stocks
          papiKO
          amorphic allele - molecular evidence
          CRISPR/Cas9
          References (4)