FB2024_04 , released June 25, 2024
Human Disease Model Report: nephrotic syndrome (postulated), stomatin-related
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General Information
Name
nephrotic syndrome (postulated), stomatin-related
FlyBase ID
FBhh0000553
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes nephrotic syndrome (postulated), stomatin-related. Nephrocytes are cells in invertebrates that are functionally analogous to the podocytes and proximal tubules of the vertebrate kidney. In a screen for fly genes required for the function of nephrocytes, one of the genes of the stomatin family in Drosophila, Mec2, was identified. This gene family has multiple members in both human and fly; the human gene NPHS2 (or PDCN, podocin) is implicated in nephrotic syndrome, type 2 (MIM:600995; see FBhh0000552). For Dmel\Mec2, RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.

In the fly, nephrocytes act in a manner analogous to human podocytes: the fly nephrocyte diaphragm functions like the mammalian slit diaphragm to regulate filtration; the nephrocytes may also function in protein reabsorption [reviewed in FBrf0220711 and FBrf0235870; see also the human disease model report 'kidney disease (fly models overview)' FBhh0000738].

None of the human stomatin family genes has been introduced into flies.

Available insertional alleles of Dmel\Mec2 are viable and fertile. Using a driver specific for expression in pericardial nephrocytes, RNAi-effected knockdown of Mec2 blocks uptake of a protein marker into the nephrocytes, results in cellular abnormalities in the nephrocytes, and disrupts the nephrocyte diaphragms. Many physical interactions for Dmel\Mec2 have been described; see below and in the Mec2 gene report.

[updated Jun. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: nephrotic syndrome
Symptoms and phenotype

The nephrotic syndrome is characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. Approximately 20% of affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure (summary by Fuchshuber et al., 1996, pubmed:8606597). [From MIM:256300, 2016.06.13]

(OMIM, 2013-)
Specific Disease Summary: nephrotic syndrome (postulated), stomatin-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

Stomatins are integral membrane proteins believed to be involved in regulating monovalent cation transport through lipid membranes (InterPro, Stomatin family, http://www.ebi.ac.uk/interpro/entry/IPR001972); they may also play a structural role within folded membrane structures (Snyers et al, 1998; pubmed:9642292).

(FlyBase Curators, 2013-)
External links
Disease synonyms
kidney disease, stomatin-related
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\Mec2
      Gene Snapshot
      Contributions welcome
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
        Comments on ortholog(s)

        Moderate-scoring ortholog of human STOML3, STOM, and NPHS2 (multiple orthologs and paralogs in both species). Dmel\Mec2 shares 57-60% identity and 75-80% similarity with human STOM and STOML3; it shares 39% identity and 58% similarity with NPHS2.

        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 (88 groups)
          Mec2
          protein-protein
          Interacting group
          Assay
          References
          Mec2 - Agpat3
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Arf1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Arl8
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Atpα
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - ATPsynγ
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - bbc
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - blw
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - cathD
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CCT3
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CCT6
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CCT7
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CCT8
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG1416
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG2065
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG2070
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG3164
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG5854
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG5885
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG7668
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG13220
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG15098
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG31729
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG33253
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - CG33303
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Chc
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Cyp12d1-p
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - drk
          anti tag coimmunoprecipitation, peptide massfingerprinting
          (Friedman et al., 2011)
          Mec2 - Dsor1
          anti tag coimmunoprecipitation, peptide massfingerprinting
          (Friedman et al., 2011)
          Mec2 - ex
          anti tag coimmunoprecipitation, peptide massfingerprinting
          (Kwon et al., 2013)
          Mec2 - FASN1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Fatp1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - fax
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Gale
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - GCS2β
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Gfat2
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Gp93
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Hel25E
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Ipo9
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - jagn
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Kap-α3
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Karyβ3
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - KdelR
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Kdsr
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Kr-h2
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Ldh
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Mcad
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - mge
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Mpcp2
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - MRP
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - mt:CoII
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Nfs1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Ost48
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - OstΔ
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - ox
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Past1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Pdk1
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          (Vinayagam et al., 2016)
          Mec2 - Pi3K92E
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          (Vinayagam et al., 2016)
          Mec2 - porin
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Pp2A-29B
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rab1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rab2
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rab5
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rab6
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rab7
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rap1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rap2l
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rdh1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rer1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rpt1
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rpt2
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Rpt6
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - S6k
          anti tag coimmunoprecipitation, Identification by mass spectrometry
          (Vinayagam et al., 2016)
          Mec2 - Scamp
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - ScsβA
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - ScsβG
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Sec61α
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - SERCA
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - sns
          two hybrid
          (Weavers et al., 2009)
          Mec2 - spidey
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - SsRβ
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Surf4
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Tapδ
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Tecr
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Tspo
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - UQCR-C2
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - Vha68-2
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - wal
          experimental knowledge based
          (Guruharsha et al., 2011)
          Mec2 - ZnT63C
          experimental knowledge based
          (Guruharsha et al., 2011)
          Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
          Mec2
          Models Based on Experimental Evidence ( 1 )
          Allele
          Disease
          Evidence
          References
          Mec2KK110818
          model of  kidney disease
          CEA
          (Zhang et al., 2013)
          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
          Mec2GD3437
          P{GD3437}
          w1118; P{GD3437}v9160
          Mec2KK110818
          P{KK110818}
          P{KK110818}VIE-260B
          Mec2NIG.7635R
          P{NIG.7635R}
          Mec2HMJ23038
          P{TRiP.HMJ23038}
          y1 v1; P{TRiP.HMJ23038}attP40/CyO
          Selected Drosophila classical alleles
          Allele
          Allele class
          Mutagen
          Publicly Available Stocks
          References (6)