FB2024_03 , released June 25, 2024
Human Disease Model Report: Adams-Oliver syndrome 3
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General Information
Name
Adams-Oliver syndrome 3
FlyBase ID
FBhh0001472
Disease Ontology Term
Parent Disease
OMIM
ADAMS-OLIVER SYNDROME 3; AOS3
Overview

This report describes Adams-Oliver syndrome 3, an automosomal dominant form of Adams-Oliver syndrome. The human gene implicated in this disease is RBPJ, a transcriptional regulator important in the Notch signaling pathway. There is a single orthologous gene in Drosophila, Dmel\Su(H), for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human gene RBPJ gene has not been introduced into flies.

Amorphic and loss-of-function mutations of Dmel\Su(H) are lethal; hemizogotes die in the pupal stage. Neurogenic phenotypes are observed.

[updated Sept. 2022 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: Adams-Oliver syndrome 3
OMIM report

[ADAMS-OLIVER SYNDROME 3; AOS3](https://omim.org/entry/614814)

Human gene(s) implicated

[RECOMBINATION SIGNAL-BINDING PROTEIN FOR IMMUNOGLOBULIN KAPPA J REGION; RBPJ](https://omim.org/entry/147183)

Symptoms and phenotype

Adams-Oliver Syndrome 3 is an autosomal dominant form of Adams-Oliver syndrome, involving cutis dysplasia of the vertex scalp and terminal limb defects, but without congenital heart defects, immune defects, or other assorted anomalies observed in other forms of Adams-Oliver syndrome (Hassed et al., 2012; pubmed:22883147). [from MIM:614814; 2022.09.26]

(OMIM, 2013-)
Genetics

Adams-Oliver syndrome 3 is caused by heterozygous mutation in the RBPJ gene on chromosome 4p15. [from MIM:614814; 2022.09.26]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

The protein encoded by RBPJ is a transcriptional regulator important in the Notch signaling pathway. The encoded protein acts as a repressor when not bound to Notch proteins and an activator when bound to Notch proteins. It is thought to function by recruiting chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins to Notch signaling pathway genes. Several transcript variants encoding different isoforms have been found for this gene, and several pseudogenes of this gene exist on chromosome 9. [ Entrez:3516 ; 2022.09.26]

(FlyBase Curators, 2013-)
External links
Disease synonyms
AOS3
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    RBPJ; recombination signal binding protein for immunoglobulin kappa J region
    D. melanogaster ortholog (based on DIOPT)
    Dmel\Su(H)
    (DIOPT, 2013-)
    Comments on ortholog(s)

    Two to one: human gene to Drosophila gene.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (46 groups)
        Su(H)
        protein-protein
        Interacting group
        Assay
        References
        Su(H)
        electrophoretic mobility shift assay, fluorescent dye label
        (Kuang et al., 2021)
        Su(H) - abd-A
        bimolecular fluorescence complementation, fluorescence microscopy
        (Bischof et al., 2018, Baëza et al., 2015)
        Su(H) - Abd-B
        bimolecular fluorescence complementation, fluorescence microscopy
        (Baëza et al., 2015)
        Su(H) - Amun
        experimental knowledge based
        (Guruharsha et al., 2011)
        Su(H) - Antp
        bimolecular fluorescence complementation, fluorescence microscopy
        (Baëza et al., 2015)
        Su(H) - asf1
        anti bait coimmunoprecipitation, western blot
        (Moshkin et al., 2009, Goodfellow et al., 2007)
        Su(H) - Caf1-105
        anti bait coimmunoprecipitation, western blot, anti tag western blot
        (Yu et al., 2013)
        Su(H) - CG3815
        anti bait coimmunoprecipitation, western blot
        (Moshkin et al., 2009)
        Su(H) - CG14710
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - CG15356
        anti bait coimmunoprecipitation, western blot
        (Moshkin et al., 2009)
        Su(H) - CG31441
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - CG31955
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - da
        two hybrid
        (Cave et al., 2005)
        Su(H) - dom
        pull down, autoradiography
        (Giaimo et al., 2018)
        Su(H) - E2f2
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - exd
        bimolecular fluorescence complementation, fluorescence microscopy
        (Bischof et al., 2018)
        Su(H) - H
        electrophoretic mobility shift assay, electrophoretic mobility supershift assay, autoradiography, two hybrid, anti tag coimmunoprecipitation, western blot, isothermal titration calorimetry, predetermined participant, pull down, x-ray crystallography, fluorescent dye label, peptide massfingerprinting, experimental knowledge based, anti tag western blot
        (Maier et al., 2023, Gagliani et al., 2022, Kuang et al., 2021, Nagel et al., 2020, Gahr et al., 2019, Smylla et al., 2019, Zacharioudaki et al., 2019, Nagel et al., 2017, Zehender et al., 2017, Yuan et al., 2016, Auer et al., 2015, Contreras et al., 2015, Praxenthaler et al., 2015, Brockmann et al., 2014, Nagel and Preiss, 2014, Rhee et al., 2014, Maier et al., 2013, Kurth et al., 2011, Maier et al., 2011, Liefke et al., 2010, Barolo et al., 2002, Morel et al., 2001, Maier et al., 1997, Brou et al., 1994)
        Su(H) - HDAC1
        anti bait coimmunoprecipitation, western blot
        (Moshkin et al., 2009)
        Su(H) - HP1c
        anti tag coimmunoprecipitation, anti tag western blot, two hybrid, western blot
        (Sun et al., 2021)
        Su(H) - Hr3
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - Hr78
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - Hsap\TBP
        anti bait coimmunoprecipitation, western blot
        (Ren et al., 2011)
        Su(H) - htk
        anti tag coimmunoprecipitation, western blot
        (Singh et al., 2019)
        Su(H) - insv
        pull down, western blot, autoradiography
        (Dai et al., 2013, Duan et al., 2011)
        Su(H) - Kdm5
        anti bait coimmunoprecipitation, western blot, pull down, autoradiography
        (Liefke et al., 2010, Moshkin et al., 2009)
        Su(H) - kto
        anti bait coimmunoprecipitation, anti tag western blot
        (Janody and Treisman, 2011)
        Su(H) - l(3)mbt
        pull down, autoradiography
        (Xu et al., 2017)
        Su(H) - lilli
        anti tag coimmunoprecipitation, anti tag western blot, pull down, molecular weight estimation by staining
        (Liu et al., 2017)
        Su(H) - mam
        three hybrid, protein three hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting, western blot
        (Gahr et al., 2019, Nagel et al., 2017, Yuan et al., 2016, Auer et al., 2015, Maier et al., 2011, Veraksa et al., 2005, Kitagawa et al., 2001, Petcherski and Kimble, 2000)
        Su(H) - MED19
        pull down, anti tag western blot
        (Jullien et al., 2022)
        Su(H) - mirr
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - N
        isothermal titration calorimetry, predetermined participant, anti bait coimmunoprecipitation, western blot, two hybrid, molecular sieving, molecular weight estimation by staining, pull down, autoradiography, anti tag coimmunoprecipitation, peptide massfingerprinting, protein three hybrid, three hybrid, anti tag western blot, cosedimentation, coimmunoprecipitation, electrophoretic mobility shift assay, electrophoretic mobility supershift assay, electron microscopy
        (Gagliani et al., 2022, Koca et al., 2022, Gahr et al., 2019, Gomez-Lamarca et al., 2018, Nagel et al., 2017, Xu et al., 2017, Yuan et al., 2016, Auer et al., 2015, Contreras et al., 2015, Brockmann et al., 2014, Mishra et al., 2014, Sachan et al., 2013, Kurth et al., 2011, Maier et al., 2011, Kelly et al., 2007, Krejci and Bray, 2007, Cave et al., 2005, Veraksa et al., 2005, Le Gall and Giniger, 2004, Kitagawa et al., 2001, Petcherski and Kimble, 2000, Kidd et al., 1998, Guo et al., 1996, Fortini and Artavanis-Tsakonas, 1994)
        Su(H) - Nap1
        anti bait coimmunoprecipitation, western blot
        (Moshkin et al., 2009)
        Su(H) - OdsH
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - Rbfox1
        anti bait coimmunoprecipitation, western blot
        (Shukla et al., 2017)
        Su(H) - Rel
        two hybrid array
        (Shokri et al., 2019)
        Su(H) - Scr
        bimolecular fluorescence complementation, fluorescence microscopy
        (Baëza et al., 2015)
        Su(H) - Sin3A
        anti bait coimmunoprecipitation, western blot
        (Moshkin et al., 2009)
        Su(H) - Sirt1
        anti tag coimmunoprecipitation, anti tag western blot
        (Horvath et al., 2016)
        Su(H) - skd
        anti bait coimmunoprecipitation, anti tag western blot
        (Janody and Treisman, 2011)
        Su(H) - Smr
        two hybrid
        (Heck et al., 2012)
        Su(H) - Su(Tpl)
        anti tag coimmunoprecipitation, anti tag western blot
        (Liu et al., 2017)
        Su(H) - Taf9
        anti tag coimmunoprecipitation, anti tag western blot
        (Xie et al., 2014)
        Su(H) - Ubx
        bimolecular fluorescence complementation, fluorescence microscopy
        (Bischof et al., 2018, Baëza et al., 2015)
        Su(H) - wap
        anti tag coimmunoprecipitation, anti tag western blot
        (Mo et al., 2023)
        Su(H) - YL-1
        two hybrid array
        (Shokri et al., 2019)
        Alleles Reported to Model Human Disease (Disease Ontology) (10 alleles)
        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
        Su(H)UAS.Tag:MYC
        P{UAS-Su(H).myc}
        Su(H)sfGFP,Tag:FLAG
        PBac{Su(H)-GFP.FLAG}
        y1 w*; PBac{Su(H)-GFP.FLAG}VK00033/TM6C, Sb1
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Su(H)RNAi.UAS.cUa
        P{UAS-Su(H).RNAi.U}
        Su(H)TRiP.cUa
        P{TRiP.Su(H).U}
        Su(H)GD1544
        P{GD1544}
        Su(H)KK101550
        P{KK101550}
        P{KK101550}VIE-260B
        Su(H)HM05110
        P{TRiP.HM05110}
        y1 v1; P{TRiP.HM05110}attP2/TM3, Sb1
        Su(H)NIG.3497R
        P{NIG.3497R}
        Su(H)RNAi.UAS.cNa
        P{UAS-Su(H).RNAi.N}
        Su(H)VDRC.cUa
        P{VDRC.Su(H).U}
        Su(H)RNAi.UAS.cRa
        P{UAS-Su(H).RNAi.R}
        Su(H)RNAi.2056.UAS
        P{UAS-Su(H).RNAi.2056}
        Su(H)HMS05748
        P{TRiP.HMS05748}
        y1 sc* v1 sev21; P{TRiP.HMS05748}attP40
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        Su(H)EY07695
        P-element activity
        y1 w67c23; P{EPgy2}Su(H)EY07695
        Su(H)T4
        ethyl methanesulfonate
        Su(H)T4/CyO
        Su(H)IB115
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        Su(H)IB115 fzy1 cn1 bw1 speck1/CyO
        Su(H)8
        amorphic allele - genetic evidence
        triethylenemelamine
        AdhUF Su(H)8 cn1 / CyO, DuoxCy dpylv1 pr1 cn2
        Su(H)1
        loss of function allele
        ethyl methanesulfonate
        In(2L)Cy In(2R)Cy DuoxCy pr1 / Su(H)1
        Su(H)2
        amorphic allele - genetic evidence
        spontaneous
        AdhF Su(H)2 / In(2L)Cy In(2R)Cy, DuoxCy Bl1 cn2
        Su(H)attP
        amorphic allele - molecular evidence
        cre recombinase
        y1 w*; TI{TI}Su(H)attP P{neoFRT}40A/CyO, P{GAL4-Hsp70.PB}TR1, P{UAS-GFP.Y}TR1
        References (5)